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Pharmacist Hasif

Monday, 28 September 2009

MD. HASIF SINHA

BASIC PHARMACY

The Key Concepts of Pharmacy

Edited by:

Md. Hasif Sinha

M.Pharm (MS in Pharmaceutical Technology)

Posted by Hasif Sinha at10:510 comments

P H A R M A C Y

Pharmacy: Pharmacy derived its name from the word Pharmakon means A Drug. Pharmacyis concerned with the manufacture, formulation, quality control, and dispensing of medicaments

used to treat disease. The majority of modern medicaments consist of tablets, capsules, andinjections, all produced under stringent conditions.

Usually only a tiny part of the product is active drug, the rest being the excipients whichprovides an appropriate vehicle for delivery to the patient.
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The art and science of preparing and dispensing drugs Place where drugs are dispensedPharmacist: Who is educated about pharmacy, prepare medicine by processing drug, give

information to the public & dispense drugs.

Mission of Pharmacy: The mission of pharmacy is to serve society as the profession responsible

for the appropriate use of medications, devices, and services to achieve optimal therapeuticoutcomes.

Pharmaceutical Care: The components of pharmacy practice which entails the direct interaction

of the pharmacist with the patient for the purpose of caring for that patients drug-related needs.Careers of the Pharmacist:

1. Production & Manufacturing2. Research & Development

3. Analysis & Testing

4. Marketing

5. Hospital Pharmacy

6. Community Pharmacy7. Academics

8. Regulatory Affairs9. Documentation, Library Information Services & Pharma

10. Journalism

11. Consultancy12. Opportunities

13. Abroad

Drug: A chemical substance used in the treatment, cure, prevention, or diagnosis of disease orused to otherwise enhance physical or mental well-being.

Crude Drug: Natural substances of plant, animal or mineral origin; which process therapeutic

properties & pharmacological actions & which have undergone no treatment other than

collection & drying.Official Drugs:

Current issue of the pharmacopoeia of a country Official used for therapeutic purposeUn-Official Drugs:

Recognized as a drug in the pharmacopoeia No current issue of pharmacopoeia of a countryNon-Official Drugs:

Possesses some medicinal properties Unofficially used for therapeutic purposes Never include in the pharmacopoeiaSynthetic Drug: The term synthetic drug strictly refers to Psychoactive substances that aremanufactured through a chemical process in which the essential psychoactive constituents are

not derived from naturally occurring substances.

Prodrugs: Prodrug is a term used to describe a compound that requires metabolic

biotransformation after administration to produce the desired pharmacologically active


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compound. The conversion of an inactive prodrug to an active compound occurs primarily

through enzymatic biochemical clevage.Medicine: Medicine is the art and science of healing. It encompasses a range of health care

practices evolved to maintain and restore health by the prevention and treatment of illness.

Any drug which has a definite dosage form, dose, therapeutic mode of action and used for the

treatment of disease is called medicine.Medication: A medication or medicine is a drug taken to cure or ameliorate any symptoms of an

illness or medical condition, or may be used as preventive medicine that has future benefits but

does not treat any existing or pre-existing diseases or symptoms.Dispensing of Medication: It is often regulated by governments into 3 categoriesi. Over the Counter (OTC) Medications, which are available in pharmacies and supermarkets

without special restrictionsii. Behind the Counter (BTC) Medications, which are dispensed by a pharmacist without needing

a doctor's prescription

iii. Prescription only Medicines (POM), which must be prescribed by a licensed medical

professional, usually a physician

Systemic Medications: Systemic drug therapy involves treatment that affects the body as a wholeor that acts specifically on systems that involve the entire body, such as the cardiovascular,

respiratory, gastrointestinal, or nervous systems. Psychiatric disorders also are treatedsystemically.

Dosage Form: A dosage form is the physical form in which a drug is produced and dispensed,

such as a tablet, a capsule, or an injectable.Loading Dose: Initial dose used to maintain plasma-drug concentration.

Maintenance Dose: Dose used to regulate plasma-drug concentration.

Standard Dose: Generally usable for all patients.

In vivo: In vivo refers to experimentation using a whole, living organism as opposed to a partialor dead organism. Animal testing and clinical trials are two forms of in vivo research.

In vitro: In vitro refers to the technique of performing a given procedure in a controlled

environment outside of a living organism.

Pharmacopoeia: An official publication which lists various drugs & therapeutic agents of currentuse with their monographs & specifies tests & standards for them (e.g. BP, USP, AP, IP).

Hospital Pharmacy: A department of hospital which deals with procurement, storage,

compounding, dispensing, manufacturing, testing, packaging & distribution of drugs.Drug Discovery:

Choose a disease [companys market strategists] Choose a drug target [receptor, enzyme or nucleic acid] Identify a bioassay [in vitro, in vivo, High throughput screening, Screening by NMR, Affinityscreening]

Find a lead compound Isolate and purify the lead compound if necessary Determine the structure of the lead compound if necessaryDrug Design:

Identify Structure Activity Relationships Identify the pharmacophore Improve Pharmacodynamics properties Improve Pharmacokinetic properties


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Drug Development:

Patent the drug Carry out preclinical trials [pharmacology studies, drug metabolism, toxicology, formulationand stability tests etc]

Design a manufacturing process [chemical and process development]

Carry out clinical trial Register and market the drug Make moneyRx: An uppercase R with its tail crossed, and was used as an abbreviation for the Latin wordrecipe = "take" (imperative), i.e. an instruction to the pharmacist to take the items listed in order

to prepare the medicine. When printing came, it was rendered as "Rx".

Posted by Hasif Sinha at10:500 comments

P H A R M A C E U T I C S

Pharmaceutics:An understanding of the basic physical chemistry necessary for the efficient design of dosage

form (Physical Pharmaceutics)The design & formulation of medicines (Dosage form design)

The manufacturing of these medicines on both a small (Compounding) scale & large(Pharmaceutical Technology) scale

The cultivation avoidance & elimination of microorganisms in medicines (Microbiology)

Pharmaceutics = Design + FormulationPurification of a substance by Crystallization:

Mixing

Filtration

EvaporationCentrifugation

Manufacture of a mixed powder:MixingSize reduction

Size separation

Manufacture of a drug extract:

MixingSize reduction

Extraction

EvaporationDrying

Size separation

DistillationPRINCIPLE OF PHARMACEUTICAL PROCESSING

Particle Size Reduction

Communication, reduction of the particle size of a solid substance to a finer state, is used tofacilitate crude drug extraction, increase the dissolution rates of a drug, aid in the formulation of

pharmaceutically acceptable dosage forms, and enhance the absorption of drugs.

The surface area is increased by particle size reduction.
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Particle Size Separation

Solid separation is a process by which powder particles are removed from gases or liquids, andhas two main aims:

To remove valuable products or byproducts

To prevent environmental pollution

Powder FlowThe largest use of powders pharmaceutically is to produce tablets and capsules. Together with

mixing and compression properties, the flow ability of a powder is of critical importance in the

production of pharmaceutical dosage form.Particle Properties:

Adhesion: Attraction between different particles (e.g. between a particle & a hopper wall)

Cohesion: Attraction between similar particles.Mixing

A unit operation that aims to treat two or more components, initially in an unmixed or partially

mixed state, so that unit (particle, molecule etc) of the components lies as nearly as possible in

contact with a unit of each of the other components. Theoretically ideal mixture is called perfect

mix.Types of mixture: There are 3 types of mixture.

Positive mixture: Positive mixtures are formed materials such as gases or miscible liquids whichmix spontaneously and irreversibly by diffusion, and tend to approach a perfect mix.

Negative mixture: With negative mixture the components will tend to separate out. Generally

more difficult to form and maintain and require a higher degree of mixing efficiency. E.g:Emulsions, Creams, and viscous suspensions.

Neutral mixture: Static in behavior, i.e. the components have no tendency to mix spontaneously.

E.g: Powders, Pastes, Ointments.

MillingMilling is the mechanical process of reducing the particle size of solid. Various terms such as

crushing, disintegration, dispersion, grinding, and pulverization have been used synonymously

with communication depending on the product, the equipment, and the process.

Milling equipments is classified as coarse, intermediate, or fine according to the size of milledproducts.

Types of Mills: Hammer Mill, Ball Mill, Fluid-Energy Mill, Roller Mill, Colloid Mill

Drying: The removal of liquid from a material by the application of heat, and is accomplished bythe transfer of a liquid from a surface into an unsaturated vapor phase.

Drying is most commonly used in-

Preparation of granulesProcessing of materials

Preparation of powder extracts

Reduce bulk & weight

Increase stability rate of the productTypes of Dryer:

Convective Drying for Wet Solids

Fixed Bed Convective DryingDynamic Convective Drying

Conductive Drying for Wet Solids

Vacuum Oven


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Vacuum Tumbling Drier

Rotation Drying of Wet SolidsRadiant heat transmission

The use of microwave radiation

Driers for Dilute Solution & Suspension

Drum DryerSpray Dryer

Freeze Drying for Heat-Sensitive Materials

Relative Humidity:

RH= (Vapour pressure of water vapour in the air 100%)/(Vapour pressure of water vapour inair saturated at the same temp.@)

Compression & Consolidation of Powdered Solids: The physics of compaction stated that thecompression & consolidation of a two-phase (solid - gas) system due to the applied force.Compression: A reduction in the bulk volume of the material as a result of displacement of the

gaseous phase.

Consolidation: An increase in the mechanical strength of the material resulting from particle-

particle interactions.Pharmaceutical Rheology

Rheology: Rheology is the study of flow, addresses the viscosity characteristics of powders,fluids, and semisolids. Materials are divided into two main categories,

Newtonian flow is characterized by constant viscosity, regardless of the shear rates applied.

Non-Newtonian flow is characterized by a change in viscosity characteristics with increasingshear rates.

Rheologic measurements are utilized to characterize the ease of pouring from a bottle, squeezing

from a tube or other deformable container, maintaining product shape in a jar or after extrusion,

rubbing the product onto & into the skin, and even pumping the product from mixing & storageto filling equipment.

Viscosity: Viscosity describes a fluid's internal resistance to flow and may be thought of as a

measure of fluid friction. The study of viscosity is known as rheology.

Velocity: Velocity is the rate of change of position in time.

Stokes Law of Velocity:v = ( 2r2g(-))/9Here, v = velocity, r = radius, g = gravitational force, = density of disperse phase, =density of dispersion medium, = viscosityBulk Density: Bulk density is a property of powders, granules and other "divided" solids,

especially used in reference to soil. It is defined as the mass of many particles of the material is

divided by the total volume they occupy. The total volume includes particle volume, inter-

particle void volume and internal pore volume.

Bulk density = (Mass of oven dry soil )/(Core volume)

Clarification

Clarification is a process that involves the removal or separation of a solid from a fluid fromother fluid.

Fluid = Liquids o/r Gases.

Types of Clarification:Filtration


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Centrifugation

In pharmaceutical processing there are two main reasons for such processes:To remove unwanted solid particles from either a liquid product or from air

To collect the solid as the product itself (e.g. following crystallization)

Filtration: The separation of an insoluble solid, from a fluid by means of a porous medium that

retains the solid but allows the fluid to pass.Filter medium: The porous membrane which is allows the liquid to flow but retains solid.

Filter cake: Solids accumulated on the filter.

Filtrate: Clear liquid passing through the filter.Slurry: Mixture of solid and liquid to be filtered.

Theory of Filtration:

Rate = (Driving force)/Resistance

Poiseuilles Equation, dv/dT = AP/((W/(A+R)))Types of Filtration:

Solid-Fluid Filtration

Solid-Liquid Filtration

Solid-Gas FiltrationFluid-Fluid Filtration

Centrifugation: Centrifugal force can be either to provide the driving force for the filtrationprocess or to replace the gravitational force in sedimentation processes.

Theory of Centrifugal Force:

F/G = 22n2d/g = 2.013 n2dSedimentation: Sedimentation is the tendency for particles in suspension or molecules in solution

to settle out of the fluid in which they are entrained, and come to rest against a wall. These forces

can be due to gravity, centrifugal acceleration or electromagnetism.

Factors affecting Sedimentation:Brownian Movement

Size of particle

Viscosity of the medium

GravityPellet: Material that has accumulated on the bottom of a tube after centrifugation is called pellet.

Supernatant: The overlying fluid is called the supernatant solution or simple the supernatant.

PHARMACEUTICAL DOSAGE FORM DESIGN

PreformulationEach drug substance has intrinsic chemical and physical characteristics that must be considered

before the development of a pharmaceutical formulation. Among these are the drugs solubility,partition coefficient, dissolution rate, physical form, and stability.

Partition Co-efficient: To produce a pharmacological response, a drug molecule must first cross abiologic membrane of protein and lipid, which acts as a lipophilic barrier to many drugs. The

ability of a drug molecule to penetrate this barrrier is based in part on its preference for lipids

[lipopholic] versus its preference for an aqueous phase [hydrophilic]. A drugs partitioncoefficient is a measure of its distribution in a lipophilic-hydrophilic phase system and indicates

its ability to penetrate biologic multiphase systems.

Partition co-efficient =(Solubility of Drug in Organic Solvent )/(Solubility of Drug in Aqueous


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Solvent)

Physical Form: The crystal or amorphous forms and the particle size of a powdered drug canaffect the dissolution rate, thus the rate and extent of absorption, for a number of drug. For

example, by reducing particle size and increasing powder fineness and therefore the surface area

of a poorly soluble drug, its dissolution rate in the gut is enhanced and its biologic absorption

increased.Stability: The chemical and physical stability of a drug substance alone, and when combined

with formulation components, its critical to preparing a successful pharmaceutical product.

ANALYTICAL PREFORMULATIONATTRIBUTE TEST

Identity Nuclear Magnetic Response [NMR]

Infra Red Spectroscopy [IRS]Ultraviolet Spectroscopy [UVS]

Thin Layer Chromatography [TLC]

Differential Scanning Calorimetry

Optical Rotation, where applicable

Purity Moisture (Water & Solvent)Inorganic Elements

Heavy MetalOrganic Impurities

Differential Scanning Calorimetry

Assay TitrationUltraviolet Spectroscopy [UVS]

High Performance Liquid Chromatography [HPLC]

Quality Appearance

OdorSolution Color

pH of Slurry (Saturated Solution)

Melting Point

Biopharmaceutics

Biopharmaceutics is the science that examines the interrelationship of the physicochemical

properties of the drug, the dosage form in which the drug is given, and the route ofadministration on the rate and extent of systemic drug absorption.

Factors that influence Biopharmaceutics:

The stability of the drug within the drug productThe release of the drug from the drug product

The rate of release or dissolution of the drug at the absorption site

The systemic absorption of the drug

Bioavailability: Bioavailability is defined as the rate and extent of the drug absorption. Thebioavailability exhibited by a drug is thus very important in determining whether a

therapeutically effective concentration will be achieved at the site or sites of action.

For intravenous administration of a drug,Directly administered into the blood

The entire drug reaches the systemic circulation

IV administrated drug is 100% bioavailable.


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For orally administered of a drug,

Completely released from the dosage formFully dissolved in the GIT fluids

Stable in solution in the GIT fluids

Pass through the GIT barrier into the mesenteric circulation without being metabolized

Pass through the liver into the systemic circulation unchangedOral administrated drug is 100% bioavailable.

AreaUnderCurve [AUC]: The total amount of active drug that reaches to systemiccirculation.Minimum Effective Conc. [MEC]: The minimal blood level at which a systemic drug exerts the

desired effect.

Maximum Therapeutic Conc. [MTC] / Maximum Safe Concentration: The maximum blood levelat which a systemic drug exerts the desired effect.

Drug Binding Proteins:

Human Serum Albumin (HAS)

1 acidic Glycoprotein (AGP)

GlobulinLipoprotein

PHARMACEUTICAL DOSAGE FORM

Tablet

A tablet is a mixture of active substances and excipients, usually in powder form, pressed orcompacted into a solid. The excipients include binders, glidants (flow aids) and lubricants to

ensure efficient tabletting; disintegrates to ensure that the tablet breaks up in the digestive tract;

sweeteners or flavors to mask the taste of bad-tasting active ingredients; and pigments to make

uncoated tablets visually attractive. A coating may be applied to hide the taste of the tablet'scomponents, to make the tablet smoother and easier to swallow, and to make it more resistant to

the environment, extending its shelf life.

The compressed tablet is the most popular dosage form in use today. About two-thirds of all

prescriptions are dispensed as solid dosage forms, and half of these are compressed tablets. Atablet can be formulated to deliver an accurate dosage to a specific site; it is usually taken orally,

but can be administered sublingually, rectally or intra vaginally.

Tablet = Active Ingredients (90-95%) + ExcipientsType of Tablets: Compressed Tablets, Multiply Compressed Tablets, Sugar Coated Tablets, Film

Coated Tablets, Gelatin Coated Tablets, Enteric Coated Tablets, Buccal & Sublingual Tablets,

Chewable Tablets, Effervescent Tablets, Molded Tablets, Tablet Triturates, Hypodermic Tablets,Dispensing Tablets, Immediate Release Tablets, Instantly Disintegrating or Dissolving Tablets,

Lyophilized Foam, Extended Release Tablets, Vaginal Tablets

Tablet Formulation:

Compatibility of drug substance with excipientsFlow ability

Compactibility

LubricityAppearance

Disintegration

Dissolution


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Manufacturing of Tablets:

Granulation: Granulation is the process of collecting particles together by creating bonds

between them. Its the process of particle size enlargement.Types of Granulation:

Direct Compression: This method is used when a group of ingredients can be blended and placed

in a tablet press to make a tablet without any of the ingredients having to be changed.Wet Granulation:

Step 1: Weighing and Blending - the active ingredient, filler, disintegration agents, are weighed

and mixed.Step 2: The wet granulate is prepared by adding the liquid binder/adhesive.

Step 3: Screening the damp mass into pellets or granules

Step 4: Drying the granulationStep 5: Dry screening

Step 6: Lubrication

Step 7: Liquid binder, but sometimes many actives are not compatible with water.

Dry Granulation: This process is used when the product needed to be granulated may be

sensitive to moisture and heat.Fluidized Bed Granulation: It is a multiple step process performed in the same vessel to pre-heat,

granulate and dry the powders. It requires only one piece of machinery that mixes all thepowders and granules on a bed of air.

Tablet Disintegration Process:

Tablet Drug dissolution Drug in solution in GI fluid Absorption Drug in BloodTablet Processing Problems:

Capping (complete separation)

Lamination (separate into 2 or 3 layers)

Picking or Striking (break when they are in sealed or turned up)Mottling (uneven color)

Weight Variation

Granule Size and Size Distribution Before Compression

Poor Flow of GranulesPoor Mixing

Hardness Variation

Double ImpressionPunch Variation

Allowed weight variations for TABLET

Average Tablet weight in mg Maximum % of difference allowed130 / Less 10

130324 7.5More than 324 5

Friability: Friability is an important factor in tablet formulation to ensure that the tablet can stay

intact and withhold its form from any outside force of pressure.

% friability = 100 ((W0-Wf))/W0Where Wo= original weight of the tablets, and Wf= final weight of the tablets after the collection

is put through the friabilator.

Friability below 0.8% is usually considered satisfactory


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Tablet Coating: Although sugar-coating was popular in the past, Modern tablet coatings are

polymer and polysaccharide based, with plasticizers and pigments included.Principles of Tablet Coating:

Coatings are necessary for tablets that have an unpleasant taste, and a smoother finish makes

large tablets easier to swallow.

Tablet coatings are also useful to extend the shelf-life of components that are sensitive tomoisture or oxidation.

Tablet Coating Defects:

Film Coating Defects: Wrinkling or Blistering, Picking, Pitting, Blooming, Mottling, OrangePeel, Bridging, Cracking, Splitting, Peeling

Sugar Coating Defects: Chipping, Cracking, Non-drying, Twinning, Uneven color, Blooming,

Sweating, and MarblingTablet Excipients Properties:

They should be inert and physically and chemically compatible with the active substance and

the other excipients being used in the formulation

They should be physiologically inert

They should not have an unacceptable microbiological burdenThey should not have a deleterious effect on the bioavailability

They should have regulatory acceptability in all countries where the product is to be markedTablet ADVANTAGES:

They are a unit dosage forms, offer the greatest dosage precision and the least content variability

Their cost is lowest of all oral dosage formsThey are the lightest and most compact

In general, the easiest and cheapest to package and ship

Product identification is the simplest and cheapest when employing embossed or monogrammed

punch faceProvide the greatest case of swallowing, with the least tendency for hang up above the stomach

Lend themselves to contain special release profile example: enteric or delayed release products

Better suited to large scale production

The best combined property of chemical, mechanical and microbiologic stabilityTablet DISADVANTAGES:

Some drugs resist compression in to dense compacts

Drugs with poor wetting, slow dissolution properties, absorption in the GIT. May difficult toformulate as a tablet

Bitter testing drugs, drugs with an objectionable odor or drugs that are sensitive to oxygen or

atmospheric moisture may require coatingSustained Release Dosage Form

Another form of coating is enteric coated tablets which are coated with a material which will

dissolve in the intestine but remain intact in the stomach. Polymeric acid compounds have been

used for this purpose with some success. Enclosing drugs in diffusion-controlled membranes isan important basic principle of controlled time release.

Types of products:Erosion tablets

Waxy matrix

Matrix erodes or drug leaches from matrix


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Coated pellets

Different pellets (colors) have different release propertiesCoated ion exchange

Osmotic pump

Insoluble coat with small hole. Osmotic pressure pushes the drug out at a controlled rate.

Benefits:For short half-life drugs, sustained release can mean less frequent dosing and thus better

compliance.

Reduce variations in plasma or blood levels for more consistent result.Problems:

A sustained release product may contain a larger dose, i.e. the dose for two or three normaldosing intervals. A failure of the controlled release mechanism may result in release of a largetoxic dose.

More expensive technology

Results:

Reduced side effects

CapsuleOne or more medicinal & inert substances are enclosed within a small shell or container which is

prepared by gelatin. Hard Gelatin and Soft Gelatin capsules are made from gelatin and fromplant-based gelling substances and modified forms of starch and cellulose.

Gelatin: Gelatin is a heterogeneous product obtained by the partial hydrolysis of collagen derived

from the skin, white connective tissue, hide portion, frozen pork and bones of animals.Properties of Gelatin:

Gelatin occurs in sheets, flakes, shreds, or as a coarse or fine powder

It is faintly yellow or amber and process slight characteristic odor and taste

When dry it is stable in air but when moist, it is subject to bacterial decompositionIt is soluble in hot water

It is insoluble in cold water, most immiscible solution, volatile and fixed oils

Capsules Sizes & Body Fill Volume:

Capsule Size Body Volume (mL)000 1.40

00 0.95

0 0.681 0.50

2 0.37

3 0.304 0.21

5 0.13

Types of Capsule:Hard Gelatin Capsule: Hard-shelled capsules are normally used for dry, powdered ingredients.

The shell of hard gelatin capsules basically consists of gelatin, plasticizers and water. Modern

day shells may, in addition, consist of preservatives, colors, opacifying agents, flavors, sugars,acids, enteric materials etc.

Parts of Hard Gelatin Capsule (1) Body (2) CapProperties of Hard Gelatin Capsule:


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Usually cylindrical in shape.

Their boundary wall is firm and rigid, not flexible.Only solid medicaments are filled into the shell.

The Hard Gelatin Capsule shell usually contains plasticizers, water, preservatives, color, flavor,

and sugar.

Hard gelatin capsule contains less moisture [1316%].It requires two steps of formulation. At first, the shell formation and then the filling processcompleted.

Volatile oil substance is not suitable for filling.Hard gelatin capsules usually contain 30600 mg.High bloom gelatins are used.

Ration of dry gelatin and dry glycerin is 1:0.4.Types of materials for filling into hard gelatin capsule

Dry solid Semisolids Liquids

Powder, Pellets, Granules, Tablets Thermo softening mixtures, Thixotropic mixtures, Pastes

Non-aqueous liquids

Preparations of Filled Hard Gelatin Capsule:

Developed and preparing the formulation and selecting the size capsuleFilling the capsule shells

Capsule sealing [optional]

Cleaning and polishing the filled capsulesSoft Gelatin Capsule: Soft-shelled capsules primarily used for oils and for active ingredients that

are dissolved or suspended in oil. Consist of liquid or semisolid matrix inside one piece of outer

gelatin shell.

Properties of Soft Gelatin Capsule:Shape: Spherical, Oval, Cylindrical, Tube

Filled medicaments: May be solid, semi-solid and liquid

Boundary wall: Soft and Flexible

Moisture content in gelatin: 0.71.3 parts of water to each parts of dry gelatinThe Gelatin Wall: Usually contain water, plasticizers and preservatives

Capsule Shell: The soft gel capsule shell may be transparent or opaque and cam be colored and

flavored if desiredCoating: The soft gel can be coated with enteric resistant or delayed release material

Formulation process: One continuous process, e.g. Fillings formulation in same time

Volatile drug substance: Suitable for fillingCapacitymay contain 0.130 mLStructureOnly the bodyGelatin Strength: Low bloom gelatin used Dry glycerin : Dry gelatin = 0.8 : 1

Classification:Orally administered soft gels

Chewable soft gels

Suck able soft gelsTwist off soft gels

Melt able soft gels

Soft Capsule Shell Components:


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Gelatin

Coloring agentOpacifier

Plasticizer

Preservatives

Core materials:Vehicles

Drug

Suspending agentSurfactant

Preservative or antioxidant

Soft Gelatin Capsule ADVANTAGES:Improved drug absorption

Increased bioavailability

Patient compliance and consumer preference

Safety potent and Cytotoxic drugs

Oils and Low melting point drugsDose uniformity for low dose drugs

Product stabilityQuality Control Tests for Capsules:

Disintegration test

Weight testContents uniformity test

Certain visual test

Micro-encapsulation: Micro-encapsulation is a process by which small particles of solids, liquids

or even gases may be encapsulated into microscopic size, ranging from several tenths of 1 -5000 in size, through the formation of thin coating of coating materials around the substance

being encapsulated.

Purposes:

Controlling the release characteristics or availability of coated materialsProviding environmental protection

Altering colloidal and surface properties

Converting liquids to solidTypes of Methods:

Air suspension

Coacervation phase separationMultiorifice centrifugal

Pan coating

Solvent evaporation

Spray drying and CongealingPharmaceutical Application:

For masking the test of bitter drugs

To facilitate selective sorptionTo prepare sustained action dosage forms

For separating the incompatible ingredients

To prevent volatilization of volatile substances


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To protect drugs from moisture and oxidation

In stabilization by conversion of dosage formBiological Application:

To reduce gastric irritation

Sustained normalization of diabetic condition

In perm selectivity of enzyme substrate and reaction productsSyrup (Liquid)

The syrup employed as a base for medicinal purposes consists of a concentrated or saturated

solution of refined sugar in distilled water. The "simple syrup" of the British Pharmacopoeia isprepared by adding 1 kg of refined sugar to 500 mL of boiling distilled water, heating until it is

dissolved and subsequently adding boiling distilled water until the weight of the whole is 1.5 kg.

The specific gravity of the syrup should be 1.33Medicated syrups are prepared by adding medicaments to, or dissolving them in, the simple

syrup.

Pharmaceutical Suspension

Pharmaceutical suspensions are solid dispersion of insoluble or sparingly-soluble drugs, in

aqueous or oily vehicles. They are intended for oral administration, topical application orparenteral administration of drugs.

Aerosol suspension of finely divided, or micronized drugs, is also another class ofpharmaceutical preparations intended for inhalation.

The insoluble basic drug, or insoluble salt or compound of a drug, is frequently used rather than

using the soluble salt, to retard absorption of the drug. This is used for the preparation ofprolonged released dosage forms to avoid frequent administration of the drug.

Some eye drops or ear drops are also prepared in suspension form for drugs which are sparingly

soluble, or using the insoluble form to prolong the time of action of the drug, such as

corticosteroid preparations.Emulsions

An emulsion is a mixture of two or more immiscible liquids. One liquid (the dispersed phase) is

dispersed in the other (the continuous phase).

Types of Phase in Emulsion:Disperse/Liquid Phase: Presents as fine droplets.

Continuous Phase: Where droplets are suspended.

Micro-emulsions: Micro-emulsions are homogenous, transparent systems that arethermodynamically stable. They form spontaneously when the components are mixed in the

appropriate ratios. They can be dispersions of oil in water or water in oil, but the droplets size is

very much smaller, 5-140 nm than in coarse emulsions.Types of Emulsion:

o/w (oil in water)

w/o (water in oil)

w/o/w (water in oil in water)Stability of Emulsion:

Cracking or Breaking

The addition of a chemical that is incompatible with the emulsifying agentBacterial growth

Temperature change

Freezing


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Flocculation and Coalescence

Phase inversionEmulsifying Agents or Emulsifier: An emulsifier is a substance which stabilizes an emulsion,

frequently a surfactant.

Types of Emulsifying Agents:

Surface active agentFinely divided solids

Hydrophilic colloids

SemisolidsPharmaceutical semisolid preparations are topical products intended for application on the skin

or accessible mucous membranes to provide localized and sometimes systemic effects at the site

of application. In general, semisolid dosage forms are complex formulations having complexstructural elements. They are often composed of two phases (oil and water), one of which is a

continuous (external) phase and the other a dispersed (internal) phase. The active ingredient is

often dissolved in one or both phases, thus creating a three-phase system.

The physical properties of the dosage form depend on various factors, including the size of the

dispersed particles, the interfacial tension between the phases, the partition coefficient of theactive ingredient between the phases, and the product rheology.

The design of a semisolid preparation is based on its ability to adhere to the surface ofapplication for a reasonable duration before they are washed or worn off.

Classification of Semisolid:

OintmentsCreams

Pastes

Gels

Ointments: Ointments are semisolid preparations intended for external application to the skin ormucous membranes. Ointments may be medicated or not. Soft semisolid preparation often

anhydrous & containing medicaments dissolved suspended or emulsified in the base. E.g.

Mineral oil, Petrolatum, and Polyethylene Glycol.

Types of Ointment Bases: They are 4 types:Oleaginous bases

Absorption bases

Water-removable basesWater-soluble bases

Creams: Creams are semisolid emulsion systems with an opaque appearance. Their consistency

and rheologic properties are based on whether the emulsion is o/w or w/o and on the nature ofthe solid in the internal phase. Semisolid emulsions consisting lipophilic phase & an aqueous

phase.

Cold Cream: Cold cream is a w/o emulsion. It deposits a thin oily layer on the skin which

inhibits water evaporation. Used in winter season.Vanishing Cream: Vanishing cream is an o/w emulsion. It is well polished preparation with pearl

like appearance. It is softer than Cold cream and disappears or vanishes immediately after

application. It is rapidly penetrates into the skin and makes it soft. Used in summer season.Pastes: Pastes are basically ointments into which a high percentage of insoluble solids have been

added. Powders such as zinc oxide, titanium dioxide, starch, and kaolin are incorporated in high

concentrations into a preferably lipophilic greasy vehicle to form a paste-like mass.


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Gels: Gels are semisolid systems in which a liquid phase is constrained within a three-

dimensional polymeric matrix in which a high degree of physical cross-linking has beenintroduced.

Suppositories

Solid, uniformly mediated, torpedo shaped formulations which melt or disintegrate & dissolved

after insertion so that the medication is released into the rectum. They are used to deliver bothSystemically-acting and Locally-acting medications.

Types of Suppositories:

Vaginal Suppositories: Commonly used to treat gynecological ailments, including vaginalinfections such as candidacies.

Rectal Suppositories: Commonly used for laxative purposes with chemicals such as glycerin or

bisacodyl, treatment of hemorrhoids by delivering a moisturizer or vasoconstrictor, delivery ofmany other systemically-acting medications such as promethazine or aspirin, general medical

administration purposes: the substance crosses the rectal mucosa into the bloodstream; examples

include paracetamol (acetaminophen), diclofenac, opiates, and eucalyptol suppositories.

Evaluation of Suppositories:

Uniformity of weight testMelting range test

Breaking testDisintegration or Dissolution test

Types of Suppository Bases:

Oily basesWater soluble bases

Emulsifying bases

Properties of Suppository Bases:

It should be good in appearanceIt should melt or disintegrate, i.e. mix and dissolve in the rectal fluids at body temperature

It should retain its shape when being handled

It should be stable on storage, i.e. it should not undergo any physical or chemical change on

storageIt should be completely nontoxic and nonirritant to the mucous membrane of the body cavity

It should release the incorporate medicaments

It should be compatible with large number of drugsIt should easily attain the shape of the mold and should not stick to the sides of the mould

Pharmaceutical Aerosols

Pharmaceutical Aerosols include pressurized Metered Dose Inhalers (MDIs), Dry PowderInhalers (DPIs), Nebulizers, Sublinguals, Skin Sprays (coolants, anesthetics, etc.) and Dental

Sprays.

Inhaler: An inhaler or puffer is a medical device used for delivering medication into the body via

the lungs. It is mainly used in the treatment of Asthma and Chronic Obstructive PulmonaryDisease.

Metered Dose Inhaler: MDI is a device that helps deliver a specific amount of medication to the

lungs, usually by supplying a short burst of aerosolized medicine that is inhaled by the patient. Itis commonly used to treat Asthma, Chronic Obstructive Pulmonary Disease, and other

Respiratory Diseases.

Basic MDI formulation components:


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Drug active

SurfactantCo-solvent

Propellant

MDI consists of 2 major components: the Canister and an Actuator.

Dry Powder Inhalers: DPIs are devices that deliver medications to the lungs to treat respiratorydiseases (asthma, bronchitis, emphysema, COPD, diabetes mellitus, and others). The medication

is commonly held either in a capsule for manual loading or a proprietary form from inside the

inhaler. Once loaded or actuated, the operator puts the mouthpiece of the inhaler into their mouthand takes a deep inhalation, holding their breath for 5-10 seconds.

Nebulizer: A device used to administer medication to people in the form of a mist inhaled into

the lungs. It is commonly used in treating cystic fibrosis, asthma, and other respiratory diseases.Sterilization (Microbiology)

Sterilization refers to any process that effectively kills or eliminates transmissible agents (such as

fungi, bacteria, viruses, spore forms, etc.) from surface, equipment, article of food or medication,

or biological culture medium.

The term sterilization, as applied to pharmaceutical preparations, means destructive of all livingorganisms and their spores or their complete removal from the preparation. Five general methods

are used to sterilize pharmaceutical products:Steam Sterilization: Steam sterilization is conducted in an autoclave and employs steam under

pressure. It is usually the method of choice if the product can withstand.

10 lb pressure [115.50C] for 30 minutes15 lb pressure [1210C] for 20 minutes

20 lb pressure [126.50C] for 15 minutes

Dry Heat Sterilization: Dry heat sterilization is usually carried out in ovens designed for this

purpose. The ovens may be heated either by gas or electricity and are generally thermostaticallycontrolled. Because dry heat is less effective in killing microorganisms than is moist heat, higher

temperatures and longer periods of exposure are required. Most pharmaceutical products are

adversely affected by heat and cannot be heated safely to the temperature required for dry heat

sterilization [about 15001600C]Filtration Sterilization: This process depends on the physical removal of microorganisms by

adsorption on the filter medium or by a sieving mechanism, is used for heat sensitive solutions.

Gas Sterilization: Some heat sensitive and moisture sensitive materials can be sterilized muchbetter by exposure to ethylene oxide or propylene oxide gas than by other means.

Ionization Radiation Sterilization: Techniques are available for sterilization of some types of

pharmaceuticals by gamma rays and by cathode rays, but application of such techniques islimited because of the highly specialized equipment required and the effects of irradiation on

product and their containers.

Sterile Products

Intravenous Therapy: IV therapy is the giving of liquid substances directly into a vein. It can beintermittent or continuous; continuous administration is called an intravenous drip. The word

intravenous simply means within a vein, but is most commonly used to refer to IV therapy.Therapies administered intravenously are often called Specialty Pharmaceuticals.Compared with other routes of administration, the intravenous route is one of the fastest ways to

deliver fluids and medications throughout the body.

Injection: An injection is an infusion method of putting liquid into the body, usually with a


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hollow needle and a syringe which is pierced through the skin to a sufficient depth for the

material to be forced into the body.An injection follows a parenteral route of administration. There are several methods of injection

or infusion:

Intradermal infusion

Subcutaneous injectionIntramuscular injection

Intravenous injection

Intraosseous injectionIntraperitoneal injection

Intravenous infusion: An intravenous infusion is a liquid administered directly into the

bloodstream via a vein.Subcutaneous injection: A subcutaneous injection is administered as a bolus into the sub-cutis,

the layer of skin directly below the dermis and epidermis.

Intramuscular injection: In an intramuscular injection, the medication is delivered directly into a

muscle.

Depot injection: A depot injection is an injection, usually subcutaneous or intramuscular, of apharmacological agent which releases its active compound in a consistent way over a long period

of time.Ampoule: An ampoule is a small glass sealed vial which is used to contain or preserve a fluid.

Modern ampoules are most commonly used to contain pharmaceutical hypodermic solutions or

high purity chemicals that must be protected from air.Vial: A vial is a relatively small glass vessel or bottle, especially used to store medication as

liquids, powders or in other forms like capsules.

The glass can be colorless or colored, clear or amber. There are different types of closure

systems, e.g. Screw vials, Lip vials, Crimp vials. A vial can have a tubular shape or a bottle-likeshape with a neck.

Saline: In medicine, saline is a general term referring to a sterile solution of NaCl in water. It is

used for intravenous infusion, rinsing contact lenses, and nasal irrigation. Saline solutions are

available in various formulations for different purposes. Salines are also used in cell biology,molecular biology and biochemistry experiments.

Catheter: In medicine a catheter is a tube that can be inserted into a body cavity, duct or vessel.

Catheters thereby allow drainage, injection of fluids or access by surgical instruments. Theprocess of inserting a catheter is catheterization. In most uses a catheter is a thin, flexible tube

("soft" catheter); in some uses, it is a larger, solid tube. ("Hard" catheter)

Eye Drops: Eye drops are saline-containing drops used as a vector to administer medication inthe eye. Depending on the condition being treated, they may contain steroids (e.g. mydriatics,

dexamethasone), antihistamines, and sympathomimetics, beta receptor blockers,

parasympathomimetics (e.g. pilocarpine), parasympatholytics (e.g. tropicamide or atropine),

prostaglandins, NSAIDs or topical anesthetics.Eye drops sometimes do not have medications in them and are only lubricating and tear-

replacing solutions and they can also contain anti-redness and similar chemicals.

Elixir (Medical Powder)A pharmaceutical preparation containing an active ingredient (such as morphine) that is

dissolved in a solution that contains some percentage (usually 40-60%) of ethyl alcohol and is

designed to be taken orally. Elixirs are often made from vodka or grappa.


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Dietary Supplement

A dietary supplement, also known as Food supplement or Nutritional supplement is a preparationintended to supply nutrients, such as Vitamins, Minerals, Fatty Acids or Amino Acids, which are

missing or are not consumed in sufficient quantity in a person's diet.

Otic Preparation

Otic preparations are sometimes referred to as ear or aural preparations. Solutions are mostfrequently used in ear, with suspensions and ointments also finding some application. Ear

preparations are usually placed in the ear canal by drops in small amounts for removal of

excessive cerumen [earwax] or for treatment of ear infections, inflammation, or pain.Water & Solutions

Purified Water: Physically processed of water to remove impurities. Distilled water & Deionizedwater is the most common forms of purified water. Other processes of water purification are:

Reverse osmosis

Carbon filtration

Micro-porous filtration

Ultra filtrationUltraviolet oxidation

Electro dialysisDistilled Water: Water which is purified by distillation process & has electrical conductivity not

more than 10 S/cm & total dissolved solids of less than 10 mg/L. Distillation involves boiling

the water and then condensing the steam into a clean container, leaving most solid contaminantsbehind. Distillation produces very pure water but does not guarantee the absence of bacteria in

drinking water.

Deionized Water: Also known as de-mineralized water that has had its mineral ions removed,

such as Cations from Na, Ca, Fe, Cu and Anions such as Cl & Br. Deionization is a physicalprocess which uses specially manufactured ion exchange resins which bind to and filter out the

mineral salts from water. Because the majority of water impurities are dissolved salts,

deionization produces high purity water. Deionization does not significantly remove hydroxide

or hydronium ions, uncharged organic molecules, viruses or bacteria.Solution: A homogenous mixture of two or more substances on molecular levels.

Standard Solution: A solution of known concentration. Standard solutions are normally used in

titrations to determine the concentration of a substance in solution. To standardize a solution ofacid we need to simply titrate it against a solution of alkali of known concentration. Standard

solutions are also commonly used to determine the concentration of an analyte species.

Saturated Solution: Solution that contain maximum amount of solutes at a particular temp,pressure & homogeneity which is destroyed due to further addition of solute.

Unsaturated Solution: [Just opposite definition of Saturated Solution]

Supersaturated Solution: A solution of a substance can dissolve no more of that substance and

additional amounts of it will appear as a precipitate. This point of maximum concentration, thesaturation point, depends on the temperature of the liquid as well as the chemical nature of the

substances involved.

Concentration: (Mass or Volume of Solute/Mass or Volume of Solution) 100%Concentration of Solution = (mass of solute in gm)/(volume of solution in dm3)

Percent Yield: % yield = (actual yield)/(theoretical yield) 100

Percent Purity: % purity = (mass of pure substance in sample)/(mass of sample) 100 = (mass of


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salt obtained)/(initial mass of impure salt) 100

Drugs Solubility: A drug substance administered by any route must possess some aqueoussolubility for systemic absorption and therapeutic response.

Dissolution Rate: The speed at which a drug substance dissolves in a medium is called

dissolution rate.

Factors affecting SOLUBILITY:Temperature

pH

Co-solventSolubilization

Complexation

Particle size controlChemical modification of the drug

Aqueous Solution: Solution where water is used as solvent or vehicle.

Benefits of Aqueous Solution:

Available

Easy to storeTastelessness

Non-toxicA wide range of materials dissolve in water

Physiologically compatible to the body

Lack of pharmacological activityFree from irritating qualities

It can be handled and used with minimum care

Non-Aqueous Solution: Solution where water is not used as solvent or vehicle.

Co-Solvency: The process of increasing the solubility of poorly water soluble electrolytes &non-polar molecules by the addition of a water miscible solvent.

Complexation: The process of increase poorly soluble drug by the interaction with a soluble

material to form a soluble intermolecular complex.

Molarity(Molar Concentration) Molality Normality

Amount of Solute per unit Volume of Solution.

C= (n/V)= (N/NAV)= (C/NA)Here, n= amount of the solute, N= number of molecules present in the volume =V, concentration

=C, NA= Avogadro constant= 6.0231023 mol1.SI units: mol/m3. The Number of Moles of Solute per kg (1000gm) of Solvent. Atoms/molecules randomly placed as in a liquid.

Amorphous: Atoms or molecules randomly placed as in a liquid.Osmosis: Flow of solvent through a semi-permeable membrane. Floe will be dilute to

Concentrate part.

Solvent ::: Dilute Solution Concentrate SolutionOrganic Compound

Composition of Organic Compound

C : Always present


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H : Nearly always present

O : Generally presentN, Halogens & S : Less commonly present

P : Rarely present

Purification of Organic Compounds:Crystallization

Sublimation

DistillationFractional distillation

Distillation under reduced pressure

Steam distillationExtraction with solvents

Chromatography

Acid, Base, pH, Titration, Indicator, Rate of Reactions

Acid & Base ConceptsCONCEPT ACID BASE

Arrhenius Concept H+ Producer OH- ProducerBronstedLowary Concept H+ Donor H+ AcceptorLewis Concept e- Pair Acceptor e- Pair Donor

pH: pH is a measure of the acidity or basicity of a solution. It is defined as the cologarithm of theactivity of dissolved hydrogen ions (H+). Hydrogen ion activity coefficients cannot be measured

experimentally, so they are based on theoretical calculations. The pH scale is not an absolute

scale; it is relative to a set of standard solutions whose pH is established by international

agreement.[1]pH - Partition Theory:

The inter relationship among this following parameters is called pH-Partition Theory.

Dissociation constant of the drug

Lipid solubility of the drugpH of the absorption site

They are the 3 important parameters dictates the absorption characteristics of drug from solution.

Buffer Solution: Compounds or mixture of compounds if they present in a solution can resistchange in pH upon addition of small quantities of acids/bases.

A buffer solution is composed ofWeak acid and its saltWeak base and its salt

Titration: Titration is a common laboratory method of Quantitative Chemical Analysis that is

used to determine the Unknown Concentration of a Known Reactant. Because volume

measurements play a key role in titration, it is also known as Volumetric Analysis. A reagent,called the Titrant or Titrator, of Known Concentration (a Standard Solution) and volume is used

to react with a solution of the Analyte or Titrand, whose concentration is not known. Using a

Calibrated Burette to add the titrant, it is possible to determine the exact amount that has beenconsumed when the endpoint is reached. The endpoint is the point at which the titration is

complete, as determined by an indicator. In the classic strong acid-strong base titration, the

endpoint of a titration is the point at which the pH of the reactant is just about equal to 7, and


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often when the solution permanently changes color due to an indicator.

Indicator: An organic dye that signals the end-point by a visual change in color.Rate of Reactions

Reaction Rates: Change in concentration of a reactant or product with time.

Rate = C/ t = (C2 C1) / (t2t1)The rate will be negative (-) for reactantsThe rate will be positive (+) for products

Factors affecting the speed or rate of a biological reaction:Concentration

Temperature

Presence of macro/micro-nutrientsPhysical state of reactants

Zero Order Reaction: A Zero-order reaction has a rate which is independent of the concentration

of the reactant(s). Increasing the concentration of the reacting species will not speed up the rate

of the reaction. The rate law for a zero-order reaction is -r = - d[A] / - dt = k, where r is the reaction rate, and k is the reaction rate coefficient with units

of concentration/time.t1/2 = [A]0 / 2k

E.g.: 2NH3 (g) 3H2 (g) + N2 (g)

First Order Reaction: A first-order reaction depends on the concentration of only one reactant (a

unimolecular reaction). Other reactants can be present, but each will be zero-order. The rate law

for an elementary reaction that is first order with respect to a reactant A is -

r = - d[A] / - dt = k[A], where k is the first order rate constant, which has units of 1/time.

t1/2 = ln (2) / k

E.g.: H2O2 (l) H2O (l) + 1/2O2 (g)

Second Order Reaction: A second-order reaction depends on the concentrations of one second-

order reactant, or two first-order reactants. For a second order reaction, its reaction rate isr = k[A]2 or r = k[A][B]t1/2 = 1 / k[A]0

E.g.: 2NO2 (g) 2NO (g) + O2 (g)

Pharmaceutical Formulation Technology

HPLC: High-performance liquid chromatography (or High pressure liquid chromatography,

HPLC) is a form of column chromatography used frequently in biochemistry and analytical

chemistry to separate, identify, and quantify compounds. HPLC utilizes a column that holdschromatographic packing material (stationary phase), a pump that moves the mobile phase(s)

through the column, and a detector that shows the retention times of the molecules. Retention

time varies depending on the interactions between the stationary phase, the molecules beinganalyzed, and the solvent(s) used.

Room Temperature (Ambient temp): Indicated by general human comfort, with the common

range of 10C (50F) to 28C (82.4 F). For scientific calculations, room temperature is taken to


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be 20 to 23.5C or 293 to 296K.

Thermal Conductivity (K): The property of a material that indicates its ability to conduct heat.

Pharmaceutical Quality Assurance and Manufacturing

Good Manufacturing Practice (GMP)Current Good Manufacturing Practice [cGMP] regulations are established by the Food and Drug

Administration [FDA] to ensure that minimum standards are met for drug product quality in the

United States. Good Manufacturing Practice or GMP (also referred to as 'cGMP' or 'currentGood Manufacturing Practice') is a term that is recognized worldwide for the control and

management of manufacturing and quality control testing of foods, pharmaceutical products, and

medical devices.

Summary of GMP principles:

The international Society of Pharmaceutical Engineers (ISPE) has succinctly summarized the

under lying principles of GMP with a set of ten rules:

Compile detailed written procedures

Follow these proceduresDocument (record) the work

Validate the systems and processes

Design and build proper facilities and equipmentMaintain the facilities and equipment

Must be competent

Maintain cleanliness

Control of qualityAudit regularly for compliance

Tropical Outline of cGMP Regulations:

General Provisions

Scope

DefinitionsOrganization and Personnel

Responsibilities of quality control unit

Personnel qualificationsPersonnel responsibilities

Consultants

Buildings and Facilities

Design and Construction FeaturesLighting

Ventilation, Air filtration, Air heating and Cooling

PlumbingSewage and Refuse

Washing and Toilet facilities

Sanitation


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Maintenance

EquipmentEquipment design, size, and location

Equipment construction

Equipment cleaning and maintenance

Automatic, mechanical, and electronic equipmentFilters

Control of Components and Drug Product Containers and Closures

General requirementsReceipt and storage of untested components, drug product containers, and closures

Testing and approved or rejection of components, drug product containers, and closures

Use of approved components, drug product containers, and closuresRetesting of approved components, drug product containers, and closures

Drug product containers and closures

Production and Process Controls

Written procedures; derivations

Charge-in of componentsCalculation of yield

Equipment identificationSampling and testing of in-process materials and drug products

Time limitations on production

Control of microbiological contaminationReprocessing

Packaging and Labeling Control

Materials examination and usage criteria

Labeling issuancePackaging and labeling operations

Tamper-resistant packaging requirements for over-the-counter human drug products

Drug product inspection

Expiration datingHolding and Distribution

Warehouse procedures

Distribution proceduresLaboratory Controls

General requirements

Testing and release for distributionStability testing

Special testing requirement

Reverse samples

Laboratory animalsPenicillin contaminations

Records and Reports

General requirementsEquipment cleaning and use log

Component, drug product container, closure, and labeling records

Master production and control records


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Batch production and control records

Production record reviewLaboratory records

Distribution records

Complaint files

Returned and Salvaged Drug ProductsReturned drug product

Drug product salvaging

cGMP for Finished Pharmaceuticals:

The regulation in 21 CFR, Part 211 contains the minimum GMP requirement for the preparation

of finished pharmaceutical product:

Active ingredient / Active pharmaceutical ingredient: Any component that is intended to furnish

pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or

prevention of disease or to affect the structure or function of the body of man or other animal.

Batch: A specific quantity of a drug of uniform specified quality produced according to a single

manufacturing order during the same cycle of manufacture.

Batch wise control: The use of validated in-process sampling and testing methods in such a way

that results prove the process has done what it purports to do for the specific batch concerned.

Certification: Documented testimony by qualified authorities that a system qualification,

calibration, validation, or revalidation has been performed appropriately and that the results are

acceptable.

Compliance: Determination through inspection of the extent to which a manufacturer of a drug

product, including those that may not be present in the finished product.

Component: Any ingredient used in the manufacture of a drug product, including those that may

not be present in the finished product.

Drug product: A finished form that contains an active drug and inactive ingredients. The term

may also include a form that does not contain an active ingredient, such as placebo.

Inactive ingredient: Any component other than the active ingredients in a drug product.

Lot: A batch or any portion of a batch having uniform specified quality and a distinctive

identifying lot number.

Lot number, control number, or batch number: Any distinctive combination of letters, numbers,

or symbols from which the complete history of the manufacture, processing, packaging, holding,and distribution of a batch or lot of a drug product may be determined.

Master record: Record containing the formulations, specifications, manufacturing procedures,


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quality assurance requirements, and labeling of a finished product.

Quality assurance: Provision to all concerned the evidence needed to establish confidence that

the activities relating to quality are being performed adequately.

Quality audit: A documented activity performed in accordance with established procedures on aplanned and periodic basis to verify compliance with the procedures to ensure quality.

Quality control: The regulatory process, through which industry measures actual quantityperformance, compares it with standards and acts on the difference.

Quality control unit: An organizational element designed by a firm to be responsible for theduties relating to quality control.

Quarantine: An area that is marked, designed, or set aside for the holding of acceptance testing

and qualification for use.

Representative sample: A sample that accurately portrays the whole.

Reprocessing: The activity where by the finished product or any of its components is recycledthrough all or part of the manufacturing process.

Strength: The concentration of the drug substance per unit dose or volume.

Verified: Signed by a second individual or recorded by automated equipment.

Validation: Documented evidence that a system [e.g. equipment, software, controls] does what itpurports to do.

Process validation: Documented evidence that a process [e.g. sterilization] does what it purports

to do.

Validation protocol: A prospective experimental plan to produce documented evidence that the

system has been validated.

A P P E N D I X [DEFINATIONS]

Acceptance Criteria: The product specification and acceptance or rejection criteria, such as

acceptable quality level and unacceptable quality level, with an associated sampling plan, that

are necessary for making a decision to accept or reject a lot or batch.

Action Limit: The established criteria, requiring immediate follow-up and corrective action if

exceeded.

Action Yield: The quality that is actually produced at any appropriate phase of manufacturing,

processing or packaging of particular drug product.


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Alert Limit: The established criteria, giving early warning of potential drift from normal

conditions which are not necessarily grounds for definitive corrective action but which requirefollow-up investigation.

Aseptic Processing Area: A controlled environment consisting of several zones, in which the air

supply, equipments and personnel are regulated to control microbial and particulatecontamination to acceptance levels.

Aseptic Area: A room or suite of rooms or special area, designed, constructed, serviced and usedwith the intension of preventing microbial contamination of the product.

Aseptic Filling: The part of aseptic processing whereby the product is sterilized separately thenfilled and packaged using sterilized containers and closures in critical processing zones.

Authorized Person: Person who is responsible for the release batches of finished product for sale.

The batch documentation of a batch of the finished product must be signed by an authorized

person from the production department and the batch test results by an authorized person fromthe QC department for batch release.

Batch Records: All documents associated with the manufacture of a batch of bulk product or

finished product.

Bio-Burden: The total number of viable microorganism on or in health care product prior to

sterilization.

Bulk Product: Any product that has completed all processing stages up to, but not including finalpackaging.

Calibration: The rest of operations that established, under specific condition, the relationship

between values indicated by an instrument or system for measuring, recording, and controlling,or the values represented by a material measure, and the corresponding known values of a

reference standard.

Change Control: A formal system by which qualified representatives of appropriate disciplines

review proposed or actual changes that might affect the validated status of facilities, systems,

equipment or process.

Changing Room: A room or suite of rooms designed for the changing of clothes and from which

a clean or aseptic area is entered.

Clean Area: An area with defined environmental control of particulate and microbial

contamination constructed and used in such a way as to reduce the introduction, generation, and

retention of contaminants within the area.

Cleaning Validation: Documented evidence that has an approved cleaning procedure will

provide equipment or area which is suitable for processing medicinal products.


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Chemical Disinfectant: A chemical or chemical solution capable of destroying microorganismthrough dehydration, alkylation, protein denaturation, oxidation, and wall permeability.

Critical Process: A process that may cause variation in the quantity of a pharmaceutical product.

Critical Area: An area with defined environment control of particulate and microbial

contamination, construction and used in such a way as to reduce the introduction, generation and

retention of contaminants within the area.

Critical Surfaces: Surfaces which come into contact with sterilized product or containers that

may lead to contamination of product contact surfaces, if not appropriately controlled.

Cross Contamination: Contamination of a starting material, intermediate product or finished

product with another starting material or product during production.

De-Contamination: The process of removing organism and rendering the object safe forhandling.

Disinfection: A process that kills or destroys most disease producing microorganisms but rarely

kills all spores.

D-Value: Sterilization exposure under a defined set of conditions that result in one logarithmic

[to the base 10] or 90% reduction in the population of particular microorganisms.

Finished Product: A product that has undergone all stages of production, including packaging inits final container and labeling.

In Process Control: Checks performed during production in order to monitor and necessary to

adjust the process to ensure that the product conforms to its specifications. The control ofenvironment or equipment may also be regarded as a part of in process control.

Integrity Test: Test to determine the functional performance of a filter system.

Intermediate Product: Partly processed material that must undergo further manufacturing steps

before it becomes a bulk product.

Laminar Air Flow: Air flowing in a single direction, through a clean room or clean room area

with uniform velocity along parallel flow lines. Laminar air flow system should provide a

homogenous air speed of 0.30 m/s for vertical flow and 0.45 m/s for horizontal flows.

Large Volume Parenterals: A sterile single dose injectable product intended for administration

through the skin or suitable parenteral route, with a normal fill volume of more than 100 ml.

Manufacture: All operations of purchase of materials and products, production, quality control,

release, storage, shipment of finished products and related controls.


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Manufacturing Process: The transformation of starting materials into finished products through asingle operation or a sequence of operation involving installations, personnel, documentation and

environment.

Marketing Authorization: A legal document issued by the competent drug regulatory authoritythat establishes the detailed composition and formulation of the product and the pharmacopoeias

or other recognized specifications of its ingredients and of the final product itself, and includes

details of packaging, labeling and self life.

Master formula: A document or set of documents specifying the starting materials with their

quantities and the packaging materials, together with a description of the procedures andprecautions required to produce a specified quantity of a finished product as well as the

processing instructions, including the in process control.

Packing: All operations, including filling and labeling, that a bulk product has to undergo in

order to becomes a finished product, sterile filling would not normally be regarded as part ofpackaging, the bulk product being the filled, but not the finally packaged, primary container.

Packaging Material: Any material, including printed material, employed in the packaging of a

pharmaceutical product, excluding any other packaging used for transportation or shipment.

Quality Drug + Quality Packaging Quality ProductAim of Packaging:

Protection

Identification

PresentationComponents of Packaging:

Container

Closure

Carton / OuterBox

Drug Packaging: Pharmaceutical blister films, high barrier thermoformable films (PCTFE,

PVDC, COC or EVOH), Al-Al Pack, Al-PVDC Pack, Al-Strip Pack, Amber Paint Bottle.Drug Packaging Hazards

Mechanical Hazards Shock or Impact damage

CompressionVibration

Abrasion

Puncture or Piercing

Environmental Hazard MoistureTemperature

Pressure

LightAtmospheric Gases

Solid airborne contamination

Biological Hazard Microbiological


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Other form of infestation

Pilferage & Adulteration risksChemical Hazard Chemical interactions

Product Regulations:

Stability Test of Drugs:Freezing & Thawing

Elevated temperature

PressureAdded chemical agents, various light sources

Phase-Volume ratio variation

Mechanical stressPharmaceutical Product: Any medicine intended for human use or veterinary product

administration to food producing animals, presented in its finished dosage form or as a starting

material for use in such a dosage form, which is subject to control by pharmaceutical legislation

in both the exporting and importing state.

Positive Pressure: Atmospheric pressure which is higher than the immediate surrounding area

usually measures in inches of water or Pascal.

Procedures: Description of the operation to be carries out, the precautions to be taken and

measures to be applied directly or indirectly related to the manufacture of the medicinal product.

Qualification of Equipments: The act of planning, caring out and recording the results of tests on

equipment to demonstrate that it will perform as intended. Measuring instruments and systems

must be calibrated.Recovery: The introduction of all or part of previous batches of the required quality into another

batch at a defined stage of manufacture.

Returned Product: Finished product sent back to manufacture.

Revalidation: A repeat of process validation to provide an assurance that changes in the process /

equipment introduced in accordance with change control procedures do not adversely affectprocess characteristics and product quality.

Specification: A document describing in detail the requirements with which the product ormaterial used or obtained during manufacture have to confirm. Specifications serve as a basis for

quality evaluation.

Standard Operating Procedure: An authorized written procedure giving instruction forperforming operations not necessarily specific to a given product or material but of a more

general nature [e.g. equipment, operation, maintenance and cleaning, validation, cleaning of

premises and environmental control, sampling and inspection etc.]. Certain SOPs may be used tosupplement product specific MPCR and BPCRs.

Starting Material / Raw Material: The substances which are use in the process of pharmaceutical


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product production.

Sterility: The complete absence of microorganisms.

Sterile Product: A product which is in a state free of viable microorganisms.

Strength: The concentration of the drug substance [e.g. weight/weight, weight/volume, or unit

dose/volume basis] or the potency, that is, the therapeutic activity of a drug product as indicated

by appropriate laboratory tests or by adequately developed and controlled clinical data.

Validation Protocol/Plan: A document describing the activities to be performed in a validation,

including the acceptance criteria for the approval of a manufacturing process or apart thereof forroutine use.

Yield:

Theoretical Yield: The quantity that would be produced at any appropriate phase ofmanufacture, processing or packaging of a particular drug product, based upon the quantity of

components to be used in the absence of any loss or error in actual production.Actual Yield: The quantity that is actually produced at any appropriate phase of manufacture,

processing, or packaging of a particular drug product.

Percentage of Theoretical Yield: The ratio of actual yield to the theoretical yield, stated as apercentage.

ZValue: The temperature change required causing an one-log [change] decrease in the D value, and its expressed in degrees Celsius.

GLOSSARY OF PHARMACEUTICAL TERMS

AActive ingredient: The ingredient or ingredients of a pharmaceutical product responsible for its

pharmacological activity [also medicament, drug substance, active pharmaceutical ingredient].

Aerosol: A dosage form that is packaged under pressure and contains therapeutically activeingredients that are released upon activation of an appropriate valve system.

Ampul: A final container that is all glass in which the open end, after filling with product, is

sealed by heat [also ampoule, ampule]Aseptic: Lacking disease-producing microorganisms; not the same as sterile.

Aseptic Processing: Manufacturing dosage forms without terminal sterilization. The dosage form

is sterile-filtered, then aseptically filled into the final package and aseptically called.

BBead: A solid dosage form in the shape of a small sphere. The dosage form generally contains

multiple beads [also pellet].

Bolus: A large, long tablet intended for administration to animals.C

Capsule: A solid dosage form in which the drug is enclosed within a hard or soft soluble

container or shell.


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Capsule, Delayed Release: A coated capsule or more commonly encapsulated granules that may

be coated to resist releasing the drug in the stomach because the drug will irritate gastric mucosaor gastric fluid will inactivate the drug.

Capsule, Extended Release: A capsule that is formulated in such a manner as to make the

contained medication available over an extended period following ingestion.

Capsule, Soft Shell: A solid dosage form in which one or more active ingredients, normally insolution or suspension or in the form of a paste, is filled into a one-piece shell.

Collodion: A liquid preparation composed of pyroxylin dissolved in a solvent mixture of alcohol

and ether and applied externally.Concentrate for Dip: A preparation containing one or more active ingredients usually in the form

of a paste or solution; it is used to prepare a diluted suspension, emulsion, or solution of the

active ingredients for the prevention and treatment of ectoparasitic infestations of animals.Creams: A semisolid dosage form containing one or more drug substances dissolved or dispersed

in a suitable base.

D

Drops, Oral: A solution, emulsion, or suspension that is administered in small volumes, such as

drops, by means of a suitable device.E

Effervescent: A dosage form containing ingredients that rapidly release CO2 when in contactwith water.

Elixir: A clear, pleasantly flavored, sweetened hydroalcoholic liquid containing dissolved active

ingredients intended for oral use.Emulsion: A two-phase system in which one liquid is dispersed throughout another liquid in the

form of small droplets.

Excipient: An inactive ingredient of a dosage form.

Extract: A concentrated preparation of vegetable or animal drug obtained by removal of theactive constituents with suitable menstrual, by evaporation of all or nearly all of the solvent and

by adjustment of the residual mass or powder to the prescribed standards.

F

Fluidextract: A liquid preparation of vegetable drug containing alcohol as a solvent, preservative,or both and so made that unless otherwise specified in an individual monograph, each milliliter

contains the therapeutic constituents of 1 g of the standard drug.

Foam: An emulsion packaged in a pressurized aerosol container that has a fluffy, semisolidconsistency when dispensed.

G

Gel: A semisolid system consisting of either a suspension of small inorganic particles or largeorganic molecules interpenetrated by a liquid.

Granules: A preparation of dry aggregates of powder particles that may contain one or more

active ingredients with or without other ingredients.

IImplant: A small sterile solid mass consisting of a highly purified drug with or without

excipients made by compression or molding and put in place by injection or incision.

Infusion, Intramammary: A suspension of a drug in a suitable oil vehicle; intended for veterinaryuse only.

Inhalation: A solution or suspension of one or more drug substances administered by the nasal or

oral respiratory route for local or systemic effect.


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Injection: A preparation intended for parenteral administration or for constituting or diluting a

parenteral article prior to administration.Irrigation: A sterile solution intended to bathe or flush open wounds or body cavities.

L

Liniment: An alcoholic or oleaginous solution or emulsion applied by rubbing on the skin for

treating pain and stiffness of underlying musculature.Lotion: A fluid suspension or emulsion applied to the surface of the skin.

Lozenge: A solid preparation that is intended to dissolve or disintegrate slowly in the mouth.

Lyophilization: Removal of water or other solvent from a frozen solution by sublimation causedby combination of temperature and pressure differentials.

M

Modified Release: A release pattern of the active ingredient from the dosage form thatdeliberately changed from that of the conventional form includes accelerated release, delayed

release, extended release, pulsatile release, targeted release, and so on.

Molded Tablet: A tablet that has been formed by dampening the ingredients and pressing them

into a mold, then removing and drying the resulting solid mass.

Mouthwash: An aqueous solution used to rinse the oral cavity.O

Ointment: A semisolid preparation intended for external application to the skin or mucousmembrane.

Ophthalmic Preparation: Drug in dosage form intended to be applied to the eye.

Ophthalmic Ointment: A sterile ointment intended for application to the eye.Ophthalmic Solution: A sterile solution, essentially free from foreign particles, suitably prepared

and packaged for instillation into the eye.

Ophthalmic Suspension: A sterile liquid preparation containing solid particles dispersed in a

liquid vehicle intended for application to the eye.Ophthalmic Strip: A sterile single-use container or sterile impregnated paper strip containing the

drug to be applied to the eye.

Orally Disintegrating: A solid oral dosage form that disintegrates rapidly in the mouth to

facilitate release of the active ingredient.Otic Solution: A solution intended for instillation in the outer ear.

Otic Suspension: A liquid preparation containing micronized particles intended for instillation in

the outer ear.P

Paste: A semisolid dosage form that contains one or more drug substances intended for topical

application. It generally contains a high concentration of solids and has a stiff consistency.Pellet: see bead [Also a solid granule or regular shape prepared by compaction or by granulation]

Pill: A solid spherical dosage form, usually prepared by wet massing technique.

Plaster: A solid or semisolid mass supplied on a backing material and intended to provide

prolonged contact with the skin.Powder: An intimate mixture of dry, finely divided drug or chemicals that may be intended for

internal [oral] or external [topical] use.

Premix: A mixture of two or more drug substances with a suitable vehicle.Pulsatile Release: A release pattern of the active ingredient from the dosage form that is

modified to release aliquots of the total drug at two or more time intervals.

R


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Rinse: A solution used to cleanse by flushing.

SShampoo: A solution, emulsion, or suspension used to clean the hair and scalp.

Soap: The alkali salts of one or more fatty acid.

Solution: A liquid preparation that contains one or more dissolved [molecularly dispersed]

chemical substances in a suitable solvent or mixture of miscible solvents; may be oral, topical,otic, and ophthalmic.

Spirit: An alcoholic or hydroalcoholic solution of volatile substances prepared usually by simple

solution or by admixture of the ingredients.Sterile: Completely lacking living [viable] microbial life.

Sterility: An acceptably high level of probability that a product processed in an aseptic system

does not contain viable microorganisms.Stick: A slender, cylindrical dosage form of rigid consistency.

Suppositories: A solid body adapted for introduction into the rectal, vaginal, or urethral orifice.

Suppository Tablet or Insert: A vaginal suppository prepared by compression of powdered

materials into a suitable shape; can also be prepared by encapsulation in soft gelatin.

Suspension: A liquid preparation that consists of solid particles dispersed throughout a liquidphase in which the particles are not soluble; may be oral, topical, otic, ophthalmic.

Syrup: A solution containing a high concentration of sucrose or other sugars.System: a dosage form developed to allow for uniform release or targeting of drugs to the body.

S

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