PHT 3101: Liquid and semisolid dosage forms

1. PHT 3101: Liquid and semisolid dosage forms

2. 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)

3. 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

4. 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 :

5. Solutions Definition of solutions and expressions of solubility advantages and disadvantages of using solutions Choice of solvent Methods of controlling solubility What a vehicle is and selection of appropriate vehicles Improvement of solubility Non aqueous solvents Formulative additives(buffers, density modifiers, tonicity modifiers,preservatives,reducing agent and antioxidants, sweetening agents, flavours and perfumes) Stability of solutions, Manufacture of solutions

6. Solution contd Principles of dispensing: Solutions for oral use Diluents Mouthwashes Nasal.oral,and aural solutions Enemas Use of oral syringes

7. 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

8. Pharmaceutical solutions for oral dosage Is based on their composition or medical use Examples and what they are: Syrups Elixirs Linctuses Mixtures Oral drops

9. Solutions for other pharmaceutical uses Examples and their uses or applications: Mouth washes and gargles Nasal solutions Ear drops enemas

10. Expression of concentrations Ways 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 examples Other ways of concn expression: Molarity Molality Mole fractions mEq,mMol

11. COMMON PHARMACEUTICAL SYRUP SIMPLE SYRUP BP: Sucrose…..66.7%w/w Water……..33.3%w/w

12. 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

13. 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

14. Choice of solvent, non-aqueous solvents; Aqueous solutions: • Water –most widely used pharmaceutical vehicle Why? Advantages and why not used in other circumstances

15. Choice of solvent • Types of pharmaceutical water. Portable water Pharmacopoeial purified water Water for injections Water for injection free of carbon dioxide/dissolved air

16. 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

17. 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

18. Co solvents contd Choice of co solvents limited in p’ceuticals: • Toxicity and irritancy Ideally suitable cosolvents –dielectric constant btwn 25 and 80. Most widely used with this range-water and EtOH Others solvents used with water:- Sorbitol,glycerol,propylene glycol, and syrup Read and makes notes on their properties and why preferred in different circumstances

19. Co solvents contd • Propylene glycol + water with co-trimoxazole in oral solution • Alcohol +Propylene glycol + syrup with paracetamol elixir • Water/isoproply alcohol with betamethasonevalerate

20. 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

21. Non-aqueous solutions • Fixed oils of vegetable origin Non volatile oils containing mainly fatty acids esters of glycerol i.e almond oil consits of Glycerides mainly of oleic acid (oil phenol inj, arachis oil for dimercaprolinj) others : olive oil, sesame oil, maize oil,cotton seed oil,soyaoil,castor oil(find out where applicable)

22. Alcohols • EtoH most widely used solvent in this class esp for external applications(> 15%v/v = antimicrobial activity) • Industrial methylated spirit has MeOH 5%V/V, denaturation property • Isopropyl alcohol

23. 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

24. Other non-aqueous • Dimethylsulfoxide • Ethyl ether • Liquid paraffin

25. Miscellaneous solvents • Isopropyl myristate • Isopropyl palmitate

26. Other formulation additives in solutions(excipients) Excipients include: buffers, density modifiers Isotonicity modifiers Viscosity enhancers Preservatives Reducing agents and antioxidants Sweetening agents Flavours and perfumes Colours

27. 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

28. 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

29. 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 painful Most used Dextrose and sodium chloride

30. 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 concn Examples : • Povidone, • Hydroxyethylcellulose,hydroxypropylcellulose ,SCMC, Cellulose, sodium alginate • Carbomers

31. Preservatives • Broad spectrum of activity gram-ve & gram+ve bacteria, yeasts, moulds (for ctrl of microbiological bioburdenin 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

32. Others excipients • Reducing agents,sweetening,flavours and perfumes Assignment: Stability of solutions Manufacture of solutions

33. End