Solutions Flashcards
Composition of a solution
Homogenous one-phase system consisting of 2/more components
- Solvent: Phase in which dispersion occurs
- Solute: Component which is dispersed as small mol/ions in the solvent
Types: Aq/Non-aq
Advantages of solutions
1) Uniform distribution of drug
2) Easy to swallow (Good for pediatrics & geriatrics)
3) Immediately available for absorption
4) < drug irritation than tablets/capsules
Disadvantages of solutions
1) Bulky - Inconvenient to store/transport
(For aq solutions)
2) Poorer stability (esp if drug prone to hydrolysis)
3) Prone to microbial growth/contamination
4) Unpleasant taste of drug more pronounced
Types of solutions
1) Aqueous solutions (Most common: H2O as solvent)
- Quality of H2O depends on preparation to be made
(Portable H2O/Purified H2O BP/H2O for injection BP/H2O free from CO2/Air)
- May not be possible to ensure complete dissolution of all ingredients at normal storage temperature
- Methods are employed to increase apparent solubility
2) Non-aq solutions
- Solvents used are non-aq in property
List methods to increase apparent solubility of compounds in an aq medium
- Cosolvency
- pH control
- Solubilization
- Complexation
- Chemical modification
- Particle size control
How does co-solvency help to increase solubility of compounds in an aq medium?
Cosolvents: Vehicles used in combination to increase the solubility of a drug
How: By addition of a H2O-miscible solvent in which the compound is also stable
- Solubility of drug is affected by the dielectric constant
(Ideal: Between 25-80*)
Eg.
Co-trimoxazole + Propylene glycol + H2O
Paracetamol + Alcohol + Propylene glycol + Syrup
Betamethasone valerate + Isopropanol + H2O
How does pH control help to increase solubility of compounds in an aq medium?
- If drug is weak acid/base, it’s degree of ionisation & consequently its solubility is influenced by the pH of the solution
Note: Ensure that chosen pH does not conflict with other product requirements
How does SOLUBILIZATION help to increase solubility of compounds in an aq medium?
How: Adding surfactant
- Use conc above cmc, but large excess undesirable
- Hydrophilic surfactants with HLB values > 15 are useful solubilizing agents
Factors affecting choice:
- Toxicity & irritancy
- Miscibility with solvent system
- Compatibility with other components
- Odour & taste
Eg. Fat-soluble vitamins + polysorbates/
Iodine + macrogol ethers
- Combination of cosolvent & solubilizing agent may be employed to improve solubility
Eg. Vit A + Polysorbate 80 + Glycerol
How much surfactant should be used?
Lowest possible concentration
- Amount of surfactant should not be excessive due to its potentially harmful effects
How to determine min [surfactant] to be used for solubilization of drug?
- Prepare a series of vials, each consisting of solvent with a constant [ ] of the surfactant
- Diff amnts of drug are added & the optical density of the mixtures is determined
- -> MDC that produces a clear solution is obtained from the graph
- The MDC values of diff [ ] of the surfactant are determined
- Plot MDC against surfactant concentration
How does COMPLEXATION help to increase solubility of compounds in an aq medium?
- Involves interaction of poorly soluble drug with a soluble material to form a soluble complex
- Complex formation should be easily reversible
Eg. iodine + polyvinylpyrrolidone
Salicylates + xanthines
How does CHEMICAL MODIFICATION help to increase solubility of compounds in an aq medium?
- Involves synthesis of soluble salts of the drug
- -> Soluble salt which may not have any activity is converted back to active base in the biological system
Eg.
Sodium phosphate salts of hydrocortisone, prednisolone & betamethasone
How does PARTICLE SIZE REDUCTION help to increase solubility of compounds in an aq medium?
- Size & shape of very small particles (<1 micron) can affect their solubility
- Particle size commonly reduced by milling
(Less commonly employed method to improve solubility)
What are non-aq solutions employed for?
1) Prepare solutions of drugs that are unstable in H2O
2) Prepare IM inj of drugs for depot therapy
Classifications of solvents for Non-Aq Solutions
1) Fixed oils of veg origin (Eg. almond/olive/soya oil)
- Use: Formulations of inj, eye-drops, liniments & oral preparations
2) Alcohols
i) For internal & external use (Ethanol)
- Commonly in low [ ] as a co-solvent with H2O in the formulation of aq solutions for oral & parenteral use
ii) For EXTERNAL use only
- Industrial methylated spirit & isopropanol
3) Polyhydric alcohol
- Commonly used as cosolvent with H2O in formulation of injections
Eg. Glycerol & Propylene glycol (Internal & External use)
Polyethylene glycols of low MW (Internal & External)
NOTE: Dipropylene glycol, diethylene glycol, ethylene glycol are VERY TOXIC!!!
4) Mineral oils & others
- More often for emulsions
- Internal & external use
- Limited use as oily & tacky nature (Veg oil prefered)
