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 betamethasone valerate

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 dimercaprol inj)
others : olive oil, sesame oil, maize oil,cotton seed oil,soya oil,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 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

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

33. End