Define solution
Homogenous one-phase system consisting of ≥2 components
Name some advantages of solutions
- Easy to swallow for children and Elderly
- homogenous mixture
- Faster onset of therapeutic activity
- Less drug irritation than tabs/caps
Name some disadvantages of solutions
- Difficult to mask unpleasant taste
- Bulky, hence inconvenient to transport and store
- Can potentially leak out of the container
- Less stable than solid dosage form as drugs are more prone to hydrolysis
- Prone to microbial growth
Solvent used in aqueous solutions
Water
List some methods which may be employed to increase apparent solubility of compounds in an aqueous medium
- Cosolvency
- pH control
- Solubilisation
- Complexation
- Chemical modification
- Particle size control
Describe cosolvency
The improvement of solubility of a weak electrolyte or non-polar compound in water by adding a water-miscible solvent in which the compound is also soluble
Vehicles used in combination to increase solubility of drugs are called cosolvents
How does cosolvency increase solubility of a compound in the vehicle?
It increases the Dielectric constant of the solvent, hence making it easier to ionise an ionic solute in the liquid, and increase solubility
The range of di-electric constant for which blends are suitable to increase solubility of a compound?
Between 25 and 80
Why is the choice of suitable cosolvents limited for pharmaceutical use?
May give rise to SE, toxicity, etc.
The concentration of the surfactant used in solubilisation should be above its critical miscellar concentration. This is known as ___________
Miscellar solubilisation
Surfactants of what HLB value range are useful solubilising agents?
> 15
Name some factors that affect choice of solubilising agents
- Toxicity and irritancy
- Miscibility with solvent system
- Compatibility with other components
- Odour and taste
Why should we avoid adding surfactants in excess?
It may be potentially harmful at high concentrations
Outline the steps to determine the minimum concentration of surfactant for solubilisation of drug
- To vials of solvent mixed with surfactant of constant concentration, add different amount of drugs and measure optical density
- Maximum drug concentration (MDC) is the max drug concentration that produces a clear solution before solution becomes cloudy, and it can be obtained from the graph of optical density against drug concentration
- Vary the surfactant concentration and plot MDC against surfactant concentration
- Use the MDC from step 2 and the graph from step 3 to find the surfactant concentration required
Complex formation should be easily ________ as most complexes are macromolecules which tend to be inactive
reversible
Name an example of complexed drug
- Povidone Iodine
2. Salicylates + Xanthines
What does chemical modification involves in making a drug compound more soluble in its solution?
Synthesis of soluble salts
How is drug particle size reduced in the manufacture of drugs?
Milling
What are the 2 reasons for non-aqueous solutions?
- Prepare solutions of drugs which are unstable in water
2. To prep IM injections of drugs for depot therapy
List the classification of non-aqueous solvents
- Fixed oils of vegetable origin
- Alcohol
- Polyhydric alcohol
- Mineral oil
- Others
What are some formulations are fixed oils of vegetable origins used in?
Injections, eye-drops, liniments, PO preps (for tasteless and odourless fixed oils)
Name the three type of alcoholic solvents and their used
- Ethanol for internal and external use. More commonly used as cosolvent for aq solutions for PO and parenteral use
- Industrial methylated spirit (Ethanol + 5% methanol) used as denaturant for ext. use
- Isopropanol for ext. use
Name some examples of polyhydric alcohols and their uses
- Glycerol for internal and external use (e.g. phenol ear drops)
- Propylene glycol for internal and external use (e.g. digoxin inj.)
- Low MW PEG for internal and external use
- DPG, DEG, ethylene glycol for external preps for veterinary and horticultural use only.
Liquid paraffin is a type of mineral oil. Why is its use as a solvent limited in pharmaceutical preparations? What is it commonly used for?
- Oily and tacky nature, hence veg oils preferred
- More often employed in formulating emulsions
