Solutions Flashcards
Definition of solution
Homogenous one-phase system consisting of 2 or more components
What is the solvent in the solution?
Phase in which the dispersion occurs; dispersion medium/continous phase
What is the solute in the solution?
Component which is dispersed as small molecules or ions in the solvent; dispersed phase
What are the 4 types of water preparations?
a) Potable water
b) Purified water BP
c) Water for injection BP
d) Water free from carbon dioxide or air
What are the 6 various methods to increase apparent solubility of compounds in an aqueous medium?
- Cosolvency
- pH control
- Solubilisation
- Complexation
- Chemical modification
- Particle size control
What is the purpose of using cosolvents?
Increase solubility of a drug
How can we improve the solubility of a weak electrolyte or non-polar compound?
Add water-miscible solvent in which the compound is also soluble
What factor affects the solubility of the drug?
Dielectric constant
What is the range of dielectric constant to make suitable blends?
25 to 80
How do you achieve micellar solubilisation?
Concentration of surfactant above cmc
What is the HLB value for hydrophilic surfactants?
> 15 solubilising agents
4 factors that affect the choice of solubilising agents?
- Toxicity and irritancy
- Miscibility with solvent system
- Compatibility with other compounds
- Odour and taste
How do you determine Minimum surfactant concentration?
- solvent with constant concentration of the surfactant is prepared in vials
- Different amts of drug added to vials and optical density of mixtures is determined.
- Maximum drug conc obtained (clear solution)
- Using same procedure, MDC values of diff surfactant conc determined
- MDC vs surfactant conc graph
- Minimum surfactant conc required to solubilise a certain drug conc determined from the plot
Most complexes used for complexation are _(size) (activity)____
macromolecules which tend to be inactive; to ensure complex formation is easily reversible
Hows does chemical modification of drug works?
Synthesis of soluble salts of the drug. The soluble salt may not have activity until it converts back to the active base in the biological system (inactive –> active)
How to reduce particle size?
Milling; but less commonly used
Why non-aq solutions might be used as a solvent for a solution?
- Prepare solutions of drugs which are unstable in water
- Prepare IM drug injections for depot therapy
Name the 4 classifications of non-aq solvents
- Fixed oils of vegetable origin
- Alcohols
- Polyhydric alcohols
- Mineral oils
Others
Uses for fixed oils of vegetable origin
- injections, eye-drops, liniments, oral prep
- tasteless and odourless for oral prep
Which alcohol is used for internal and external use?
Ethanol; low conc; as cosolvent w water in formulation of aq solns for oral and parenteral use
Which alcohols is used for external use only?
- Industrial methylated spirit (ethanol w 5% methanol as a denaturant)
- Isopropanol
Use of polyhydric alcohols?
- Cosolvent with water in formulation of injections
Types of polyhydric alcohols
- Glycerol
- Propylene Glycol
- PEG of low MW
All for internal and external use
When are mineral oils used?
Formulation of emulsions.
Limited use as solvent as it is oily and tacky nature; vege oils generally preferred
Example of mineral oil?
Liquid paraffin (internal and external use)
What are the ‘others’ in the classification of non-aq solvents?
NOT FOR INTERNAL USE
- Xylene (solvent for ear drops)
- Ethyl ether (cosolvent w alcohol, extraction of crude drugs)
- Isopropyl myristate, isopropyl palmitate (cosmetic pdts)
- Dimethylsulphoxide, dimethylformamide, dimethylacetamide (veterinary pdts)
- Kerosene (solvent for insecticides)
What are the common additives of a pharmaceutical solution?
- Buffers
- Colours
- Sweetening agents
- Flavours and fragrances
- Preservatives
- Antioxidants
- Isotonicity modifiers
- Density modifiers
Why are buffers required in a solution?
Resist any change in pH when acid/alkali is added to the solution
seen in eye, nasal, injections
e.g carbonates, citratesm gluconates
Why are colours employed in a solution?
- Attractiveness; easy identification of products
What affects the stability of the colours?
pH, UV radiation, presence of oxidizing/reducing agents
What is considered natural colours?
variation in chemical composition and is less stable; BUT more widely accepted
e.g. carotenoids, chlorophylls, anthocyanins
What is considered synthetic colours?
‘Coal tar’ dyes
Brighter colour and more stable
e.g. sodium salts of sulfonic acids
2 types of sweetening agents
- Natural (sucrose, fructose)
- Artificial (aspartame, saccharin)
What is considered an artificial sweetener?
Intense sweetener (<0.2%) May have bitter or metallic after-taste
Why are flavours and fragrances used in a solution?
Flavours for oral products - more palatable
Fragrances - improve appeal of products
can be natural or synthetic
Function of isotonicity modifiers
Adjust tonicity of large vol solutions for parenteral and ophthalmic use
Function of density modifiers
Adjust density of spinal anaesthetics
advantages of solutions as an oral dosage form?
- uniform distribution of drug
- easy to swallow
- drug immediately available for absorption
- less drug irritation than tablets/capsules
disadvantages of solutions as an oral dosage form?
(1) bulky and inconvenient to transport/store
(2) poorer stability, esp drugs that are prone to hydrolysis
(3) prone to microbial contamination/growth
(4) unpleasant taste of drug is more pronounced
(2) , (3), (4) = seen in aq solution
for what type of drugs can we use pH control to increase apparent solubility?
- drugs that are weak acid/ weak base: degree of ionisation affects solubility
- but need to ensure pH of solution does not conflict with other product requirements
the solubilising agents are usually what type of surfactants?
nonionic surfactants
- macrogol ethers etc
for non-aq solutions, fractionated coconut oil is used as a solvent for what drug?
phenoxymethylpenicillin
what are the polyhydric alcohol used for non-aq solution that are not used for humans
diethylene glycol, dipropylene glycol, ethylene glycol
how are pharmaceutical solutions manufactured?
- propeller mixer (for less viscous)
- turbine mixer (for more viscous)
- paddle mixer (more viscous)
what are some properties that can be evaluated for quality of a solution?
- drug content (this is regardless of ROA)
- density (spinal)
- tonicity (injection IV, eye drops)
- viscosity (on skin)
- clarity/particulate matter (IV injection, eye drop)
- colour (ensure right tone/shade)
- sterility (eye drops, IV injection)
