pharmaceutics and biopharmaceutics

Pharmaceutics and Biopharmaceutics

Manufacturing Versus Compounding

Manufacturing1. Utilizes large-scale

production manufacturing plants

2. Regulated NDAs/ANDAs to market

Compounding1. Practiced using small-

size equipment in small pharmacy areas

2. Requires a prescription. Compounded prescriptions are exempt from NDAs.

Manufacturing Versus Compounding

Manufacturing3. Manufacturers have

extended patent protection for chemical patents, process patents, and use patents.

4. Manufactured products are designed to meet the vast majority of patient needs (97%-99%)

Compounding3. Pharmacists generally

have no patent protection.

4. Compounding meets unique needs (often critical) for very small patient populations (1%-3%).

Biopharmaceutics

“ The Biologic response to a drug is the result of an

interaction between the drug substance and functionally important cell receptors or

enzyme systems.”

Biopharmaceutics

“ The area of study embracing this relationship between the physical,

chemical and biological substances as they apply to drugs, dosage

forms, and to drug action is termed BIOPHARMACEUTICS.”

Biopharmaceutics

Requirements for a drug to exert its biological action:1. It must be transported by the body fluids.2. It must traverse the required biologic membrane barriers.3. It must escape widespread distribution to unwanted

areas.4. It must endure metabolic attack. 5. It must penetrate in adequate concentration to the sites

of action.6. It must interact in a specific fashion, causing an alteration

of cellular function.

Biopharmaceutics

• Pharmacokinetics versus Pharmacodynamics

• ADME• Absorption – uptake into the circulation• Bioavailability – rate and extent of systemic

absorption• Question: 100% absorbed = 100% bioavailable?

Bioavailability data

1. The amount or proportion of drug absorbed from a formulation or dosage form

2. The rate at which the drug was absorbed3. The duration of the drug’s presence in the

biologic fluid or tissue; and, when correlated with patient response

4. The relationship between drug blood levels and clinical efficacy and toxicity

Terms Used To define The Type or Level Of “Equivalency” Between Drug Products

Pharmaceutical Equivalents -are drug products that contain identical amounts of the identical active ingredient.

Example: the same salt or ester of the same therapeutic moiety

Pharmaceutical Alternatives - are drug products that contain the identical therapeutic moiety, or its precursor, but not necessarily in the same amount or dosage form or as the same salt or ester.

Bioequivalent Drug Products - are pharmaceutical equivalents or pharmaceutical alternatives whose rate and extent of absorption

do not show a significant difference when administered at the same molar dose of the therapeutic moiety under similar experimental conditions, either single dose or multiple dose.

Terms Used To define The Type or Level Of “Equivalency” Between Drug Products

Therapeutic Equivalent - has been used to indicate pharmaceutical equivalent which, when administered to the same individuals in the same dosage regimens, will provide essentially the same therapeutic effect.

The most common experimental plan to compare the bioavailability of two drug products is the

simple crossover design study.

(12 to 14 individuals, males between 18 to 40 years, same height and weight)

Biopharmaceutics

Identification of a new drug entity Pre – Clinical Stage Clinical Stage

– Phase I - “Is the drug safe?”– Phase II - “Does the drug work?”– Phase III - “How well does it work?”– Phase IV - Post marketing studies

Route of administration

* Local versus systemic effects1. Oral2. Sublingual3. Parenteral

i. Intravenousii. Intrarterialiii. Intracardiaciv. Intraspinal

Routes of Administration

v. Intraosseousvi. Intradermalvii. Subcutaneous (2 mL or less) - forearm, upper arm, thigh or natesviii. Intramuscular (2 – 5 mL) – gluteal or lumbar

4. Epicutaneous5. Transdermal6. Conjunctival7. Intraocular8. Intranasal9. Rectal10. Vaginal11. Urethral

Rationale for Dosage Form Design

1. Mechanism for safe and convenient delivery of drug2. Protection from destructive factors3. Masking of taste and odor4. Appropriate liquid dosage forms5. Rate – controlled drug action6. Insertion into body orifices7. Optimal drug action from topical administration or

through inhalation therapy8. Placement of drugs directly into bloodstream

Dosage Forms

Tablets Capsules Solutions Suspensions Syrups Modified – release dosage forms

– Controlled – release, sustained action, long acting, timed release, timed delay, sustained action

Parenteral Products

Administered directly into the bloodstream or a specific organ / area

General types:1. Drug injection

2. Drug for injection

3. Drug injectable emulsion

4. Drug injectable suspension

5. Drug for injectable suspension

Parenteral Drugs

Advantages:

1. When rapid drug action is desired

2. When patient is uncooperative, unconscious or unable to accept or tolerate oral medication

3. When drug is ineffective by other routes

Parenteral Drugs

Disadvantages:

1. Pain factor

2. Requires administration by a healthcare professional

3. Immediate occurrence of toxic effects

4. Difficult removal from the body

5. More expensive

Timan-i

Body fluids are more receptive to drugs in aqueous vehicle than in oily one.

Slow absorption means prolonged drug action– Depot or repository injection

Requirement: Sterility

Parenteral Drugs

Solvents and Vehicle for Injections:1. Water for Injection, USP

- purified by distillation or by reverse osmosis- pyrogen-free but not required to be sterile

2. Sterile Water for Injection, USP- sterilized and packaged in single – dose containers- pyrogen-free

3. Bacteriostatic Water for Injection- sterile water for injection containing one or more suitable

antimicrobial agents (benzyl alcohol)

Parenteral Drugs

Solvents (Continuation) Normal Saline Solution (NSS) Bacteriostatic NSS 5% Dextrose in water Ringers / Lactated Ringer’s Solution (KCl,

NaCl, CaCl2 + Na Lactate)

DOSAGE FORM/DRUG DELIVERY SYSTEM APPLICATION

Route Of Administration Primary Dosage Forms

oral tablets, capsules, solutions, syrupselixirs, suspensions,magmas, gelsand powders

sublingual tablets, troches or lozenges

parenteral solutions, suspensions

epicutaneous/transdermal ointments, creams, infusion pumpspastes, plasters, powders, aerosolslotions, transdermal patches, discs

conjunctival contact lens inserts, ointments

intraocular/intraaural solutions, suspensions

intranasal solutions, sprays, inhalants, oint.

Intrarespiratory aerosols

DOSAGE FORM/DRUG DELIVERY SYSTEM

APPLICATION

Route Of AdministrationPrimary Dosage Forms

rectal solutions, ointments, suppositories

vaginal solutions, ointments, emulsion foams, tablets, inserts, suppositories, sponge

urethral solutions, suppositories

Routes Of Drug Administration

TERM SITE

oral mouth

peroral (per os, p.o.) gastrointestinal tract via mouth

sublingual under the tongue

parenteral other than GIT (by injection)

intravenous vein

intraarterial artery

intracardiac heart

intraspinal/intrathecal spine

intraosseous bone

intraarticular joint

intrasynovial joint-fluid area

intracutaneous/intradermal skin

subcutaneous beneath the skin

intramuscular muscle

Routes Of Drug Administration

TERM SITE

epicutaneous (topical) skin surface

transdermal skin surface

conjunctival conjunctiva

intraocular eye

intranasal nose

aural ear

intrarespiratory lung

rectal rectum

vaginal vagina

urethral urethra

Factors Affecting Dosage Form Design

1. Physical and Chemical properties of the drug2. Dose of the drug3. Intended route of administration4. Type of drug delivery system desired5. Desired therapeutic effect6. Physiologic release of drug at absorption site7. Pharmacokinetics and Pharmacodynamics of

the drug* Also holds true in compounding

Factors That Determine A Dosage Regimen

Activity, ToxicityPharmacoknetics

Minimum therapeutic dose Absorption

Toxic Dose Distribution

Therapeutic index Metabolism

Side effects Excretion

Dose-response relationship

Clinical Factors Other Factors

Clinical State of patientManagement of Therapy

Age, weight, urine pH Multiple drug therapy Tolerance-dependence

Condition being treated Convenience of regimen Pharmacogenetics-

idiosyncrasy

Existence of other disease states Compliance of patient Drug interactions

DosageRegimen

Containers

1. Ampoule / Ampul / Ampoul- Sealed by fusion of the glass containers under aseptic

condition- Neck portion that easily separates from the body of the

container without fragmentation of the glass- Once opened, any unused portion may not be retained and

used at a later time

2. Vials- With rubber closures to permit the penetration of a

hypodermic needle without the removal or destruction of the closure.

- Resealable

3. Pre – filled syringes

Pagbantay!

Because it is impossible in practice to transfer the entire volume of a single –

dose container, slight excess in volume of the content over the labeled size or volume of the

package is permitted.

Topical Preparations

Drugs should penetrate and be retained in the skin for a period of time

Treatment is based on qualitative measures Factors that affect product type and selection

of appropriate base:– Emollient and Occlusive effects– Ease of application and removal

Ointments, creams, pastes (greater occlusive property and useful in serous discharges)

How A Drug Passes Through The Body

1. Absorption = The site at which a drug enters the body affects its rates of absorption

a. Skin c. Digestive Tract

b. Lungs d. Bloodstream

2. Distribution = Most drugs enter the bloodstream; many are then distributed to

cells of various organs

a. Bone e. Glands

b. Nerves f. Heart

c. Muscles g. Cells

d. Brain h. Other organs

3. Metabolism = A drug is partially broken down, usually in the liver, before or after distribution

a. Liver

4. Elimination = Finally, a drug is eliminated, mainly via kidneys, but also in stools

and tears or through breathing

a. Breast milk c. Tears

b. Saliva d. Sweat

Some Factors Which Can influence The Bioavailability Of Orally Administered Drugs

I. Drug Substance Physiochemical Properties

II. Pharmaceutical Ingredients and Dosage Form Characteristics

III. Physiologic Factors and Patient Characteristics


I. Drug Substance Physiochemical Properties

A. Particle Size

B. Crystalline or Amorphous Form

C. Salt Form

D. Hydration

E. Lipid/Water Solubility

F. pH and pKa


II. Pharmaceutic Ingredients and Dosage Form Characteristics

A. Pharmaceutical Ingredients

1. Fillers 7. Surface Active Agents

2. Binders 8. Flavoring Agents

3. Coatings 9. Coloring Agents

4. Disintegrating Agents 10. Preservative Agents

5. Lubricants 11. Stabilizing Agents

6. Suspending Agents


B. Disintegration Rate (Tablets)

C. Dissolution Time of Drug in Dosage Form

D. Product Age and storage Conditions

III. Physiologic Factors and Patient Characteristics

A. Gastric Emptying Time

B. Intestinal Transit Time

C. Gastrointestinal Abnormality or Pathologic Condition

D. Gastric Contents

1. Food

2. Other Drugs

3. Fluid

E. Gastrointestinal pH

F. Drug Metabolism (gut and during first passage through liver)

pharmaceutics and biopharmaceutics

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