PHT 3101: Liquid and semisolid dosage forms

Liquid and semisolid dosage forms

What to cover:• Solutions• Emulsions• Suspension • Ophthalmic ,otic and nosal preparations• Ointments ,creams and gels• Suppositories and inserts• QA(QC and cGMP)

Course aim

• To prepare the students with the relevant knowledge, skills and attitudes, skills and attitudes to competently formulate and manufacture and evaluate liquid and semi-solid dosage forms

Course outcomes

The students will be able to:• describe the various liquid and semi-solid dosage

forms• formulate liquid and semi-solid preparations• perform QA and QC on liquid and semi-solid dosage

forms according to Pharmacopoeia specifications• apply GMP in liquid and semi-solid dosage form

manufacture:

Solutions

Definition of solutions and expressions of solubility advantages and disadvantages of using solutionsChoice of solvent Methods of controlling solubilityWhat a vehicle is and selection of appropriate vehiclesImprovement of solubilityNon aqueous solventsFormulative additives(buffers, density modifiers, tonicity modifiers,preservatives,reducing agent and antioxidants, sweetening agents, flavours and perfumes)Stability of solutions,Manufacture of solutions

Solution contdPrinciples of dispensing:Solutions for oral useDiluentsMouthwashesNasal.oral,and aural solutionsEnemas Use of oral syringes

Solutions Definition:

Homogenous mixture=two or more components

Dissolved in one or more solutes dissolved in one or more solvents

Usually solids in liquids

solvents mainly aqueous can be oily alcoholic and some other solvent

Pharmaceutical solutions for oral dosage

Is based on their composition or medical useExamples and what they are:SyrupsElixirsLinctusesMixturesOral drops

Solutions for other pharmaceutical uses

Examples and their uses or applications:

Mouth washes and garglesNasal solutionsEar dropsenemas

Expression of concentrationsWays in which strength of pharmaceutical solutions are expressed.Amnt of drug in 5ml teaspoonful/percentage strength %w/v, %w/w,%v/v,%v/w .find out what these expressions mean and derive your own examplesOther ways of concn expression:MolarityMolalityMole fractionsmEq,mMol

COMMON PHARMACEUTICAL SYRUP

SIMPLE SYRUP BP:Sucrose…..66.7%w/wWater……..33.3%w/w

Advantages of solutions as an oral dosage form

• Liquids are easier swallow (paed/ geriatrics)• Therapeutic response faster • Are homogenous system and drug uniformly

distributed• Irritation by certain drugs (ASA, Kcl) reduced

Disadvantages of solutions as an oral dosage form

• Bulky, inconvenient to transport and store• Ingredients in solution unstable, shorter shelf

life• Suitable media for mos growth• Measuring accurate dose difficulty by

individuals• Unpleasant taste more pronounced

Choice of solvent, non-aqueous solvents;

Aqueous solutions:• Water –most widely used pharmaceutical

vehicleWhy? Advantages and why not used in other

circumstances

Choice of solvent

• Types of pharmaceutical water.Portable waterPharmacopoeial purified waterWater for injectionsWater for injection free of carbon

dioxide/dissolved air

Improvement of aqueous solubility

• Water –not possible to completely dissolve all ingredients at normal storage/room temps

• Over wide pH range readily dissolve strongly ionized materilas

• Weak acid and weak bases adequately dissolve at favorable pH

• Note concn of any material not close to limit of solublity

Methods used to improvement of aqueous solubility

• Cosolvents: vehicles used in combination to increase solubility

Solubility in mixed solvents > individual solvent

Solubility of weak electrolyte or non-polar compound in water –improved by altering polarity of the solvent.

Addition of another solvent both miscible with water and in whc the compound is soluble

Co solvents contd

Choice of co solvents limited in p’ceuticals:Toxicity and irritancyIdeally suitable cosolvents –dielectric constant btwn

25 and 80.Most widely used with this range-water and EtOHOthers solvents used with water:-Sorbitol,glycerol,propylene glycol, and syrup Read and makes notes on their properties and why

preferred in different circumstances

Co solvents contd

• Propylene glycol + water with co-trimoxazole in oral solution

• Alcohol +Propylene glycol + syrup with paracetamol elixir

• Water/isoproply alcohol with betamethasone valerate

Other methods used to improvement of aqueous solubility

• pH control• Solubilization ( addition of surface active agents,

micelles, hydrophilic surfactants’ HLB> 15 are solubilizers and their pharmaceutical applications)

• Complexation• Chemical modification• Particle size control

Non-aqueous solutions

• Fixed oils of vegetable originNon volatile oils containing mainly fatty acidsesters of glycerol i.e almond oil consits of Glycerides mainly of oleic acid (oil phenol inj,

arachis oil for dimercaprol inj)others : olive oil, sesame oil, maize oil,cotton

seed oil,soya oil,castor oil(find out where applicable)

Alcohols

• EtoH most widely used solvent in this classesp for external applications(> 15%v/v =

antimicrobial activity)• Industrial methylated spirit has MeOH 5%V/V,

denaturation property • Isopropyl alcohol

Polyhydric alcohols

• A glycol=an alcohol with 2-OH groups per molecule

• Rarely used internally • Exceptional is propylene glycol used in

combination with water or glycerol as cosolvent• LMW PEGS(polyethylene glycols) or macrogols• Others find out• Glycerol =a tri-OH groups alcohol

Other non-aqueous

• Dimethylsulfoxide• Ethyl ether• Liquid paraffin

Miscellaneous solvents

• Isopropyl myristate• Isopropyl palmitate

Other formulation additives in solutions(excipients)

Excipients include: buffers, density modifiersIsotonicity modifiersViscosity enhancersPreservativesReducing agents and antioxidantsSweetening agentsFlavours and perfumesColours

Buffers

• Added substances that enable the solution to resist any change in pH shd an acid or an alkali be added

• Choice dependable on pH and buffering capacity required

• P,ceutically acceptable buffering based on:Carbonates,citrates,gluconates,lactates,phosphates

or citrates (and borates for external use)• Solutions of drugs (weak electrolytes)• Many body fluids

Density modifiers

• Used in formulating spinal anaesthetics• Lower density than CSF tend to rise after

injection• Higher density fall• Ctrl of inj density and position of the operating

table enable control of the site to be anaesthetized

• Terms of expression • Isobaric, hypobaric and hyperbaric• i.e Dextrose

Isotonicity modifiers

Required in formulating solutions isosmotic with body fluids for solutions for:

• injection• Application to mucous membranes • Ophthalmic use in large-volumes otherwise

irritant and painfulMost used Dextrose and sodium chloride

Viscosity enhancers• Increase time of contact at site/area of

application as in eyes and skin• Increase palatability• Are non-ionic, ionic • Are used in low concnExamples :• Povidone, • Hydroxyethylcellulose,hydroxypropylcellulose,SCMC, Cellulose, sodium alginate• Carbomers

Preservatives

• Broad spectrum of activity gram-ve & gram+ve bacteria, yeasts, moulds (for ctrl of microbiological bioburden in formulation)

• Low toxicity for human• Good solubility in water; low oil solubility• Stable ,effective over wide ph range,

compatible with other excipients• Non-volatile,odourless and tasteless

Others excipients

• Reducing agents,sweetening,flavours and perfumes

Assignment:Stability of solutionsManufacture of solutions

End