Solutions Flashcards
What is a binary solution?
A mixture of only 2 components:
Solute + solvent
What is a solution?
- Chemical and physical homogenous minute of 2 or more components
- A 1 phase system
Why is a solution also called a molecular dispersion?
The solute is dispersed as molecules or ions in the solvent
What are examples of where the solute is present in a greater amount than the solvent?
In syrups
What are the steps in forming a solution?
1) abstraction of solute molecule. This depends on the strength of the crystal lattice. This consumes energy
2) creation of cavity in solvent molecule. This depends on the cohesive forces of the solvent. This also consumes energy
3) insertion of solute molecule into solvent. This liberates energy. The larger the excess of this liberated energy, the more soluble the solvent
What are the main solutions of focus in these lecture series
Gas in liquid e.g. Carbonated water
Liquid in liquid e.g. Alcohol in water
Solid in liquid e.g. Aqueous sodium chloride solution
What are the advantages of solution dosage forms?
Easy to swallow: has paediatric and geriatric use
Rapid onset of action: drug is immediately available for absorption
Uniform drug distribution: solution is a homogenous mixture
Reduced local irritation: immediate dilution
Various routes of administration possible: oral, inhalation, IV, IM, etc
What are disadvantages of solution dosage forms?
Bulky, inconvenient to transport and store
Stability issues: esp. For drugs prone to hydrolysis
General reduced shelf life compared to solid form of same drug
Prone to microbial growth: preservative required
Dosing issues: patient may find it hard to measure 3.33ml
More pronounced taste if drug than if it were in solid form: requires flavourants
What are some pharmaceutical solvents?
Water Fatty oils Alcohols Dimethylsulphoxide Ethyl ether Xylene
What is the most widely used aqueous vehicle and why?
Water
- high physiological compatibility
- lack of toxicity
- high dielectric constant (allows dissolution of wide range of drugs)
What are the disadvantages of using water as a solvent?
- lack of selectivity during drug dissolution
This complicates the extraction of unwanted substances like inorganic salts and organic impurities
What are the types of pharmaceutical water?
Purified water (used for boiling/cooling, distillation, deionisation, reverse osmosis) Water for injections (used for Pareneteral formulations: e.g. Formulation of drugs sensitive to CO2 like phenobarbitone sodium, aminophylline, or drugs sensitive to oxidation like apomorphine and ergotamine maleate)
What are the main approaches to improve aqueous solubility?
Co solvency PH control Solubilisation Complexation Chemical modification
How does co solvency improve aqueous solubility?
We can change the dielectric constant of the solvent to make it more compatible with the drug however the choice of cosolvent is limited in pharmaceutical use. E.g. For oral administration you should avoid a toxic cosolvent
How does pH control improve aqueous solubility?
A weakly acidic or weakly basic drug has an intrinsic pKa value. This makes them prone to change their proportion of ionisation depending on the pH of the environment.
We can change the pH to favour a higher proportion of ionisation making it more dissolvable in aqueous solvents
However we should be careful that the chosen pH of the formulation does not conflict with other product requirements like issues with stability
How does solubilisation improve aqueous solubility?
We can add surfactants into the formulation (generally with HLB>15) these include simple micelles, liposomes, liquid crystals, or cyclodextrins.
These molecules have a polar and non polar portion and will bind to the drug and the solvent to help solubilise it
How does complexation improve aqueous solubility?
We can add a hydrophilic complex to the poorly soluble drug to make it more soluble however this needs to be reversible in order to allow the drug to cross through the biological membrane after it has dissolved and reached its target site
How does chemical modification improve solubility?
We can use the salt form of water insoluble drugs as they are more soluble. E.g. Sodium phosphate salts of hydrocortisone, prednisolone and betamethasone are often used
Why are non aqueous solutions used?
To overcome solubility and stability issues associated with aqueous systems
Have the ability of exhibit sustained release properties (e.g. Oily injections, oily eye drops)
What factors need to be considered when working with non aqueous solutions.
Toxicity, irritancy, flammability, cost, stability, compatibility with other ingredients
What does the choice of a non aqueous solvent depend on?
Route of administration
Topical > oral > Pareneteral
What fatty oils are used as non aqueous solvents?
Fatty oils = fatty acid esters of glycerol
E.g.
Almond oil, arachis oil, olive oil, sesame oil, maize oil, soya oil, castor oil,
Many are suitable for Pareneteral use
Which oil is used for injections?
Ethyl oleate: it is less viscous, easily injectable
What oil is used for oral administration?
Fractionated coconut oil
What oil is used for external preparations?
Unpleasant oils, unless they are formulated as an emulsion then they can be considered for oral use as well (provided they are non toxic)
What are the advantages of using lipid solutions for oral use?
Lipids can act as a solvent for lipophilic drugs
There is no dissolution required as the drug enters the GIT in solution form (normally this dissolution would have been a rate limiting step)
Lipid solutions are useful for poorly water soluble drugs with low bioavailability and high lipid solubility
How is the bioavailability improved for lipid solutions?
In a lipidic solution, when the fats are dissolved the drug does too.
This then goes into the lymphatic network.
This is a good network for the transport of poorly water soluble drugs and those which usually go through first pass metabolism.
This lymp carries a lot of your white blood cells and other fluids.
Capillaries are a bit leaky, so some molecules can leak out.
This system is lipid based and carries stuff back.
We can Hijack the lymphatic transport for our poorly soluble drugs.
The lymphatic system does not go through the liver hence avoiding first pass metabolism.
Lymph goes straight into venous system near the heart (sub clavian and superior vena cava) and then body
Thus bioavailability is increased.
How are lipids absorbed?
Lipase enzyme binds to the lipid droplet to form a colipase/lipase complex. Liquid crystalline layers can be seen at the droplet surface.
Endogenous bile salts and phospholipids then bind, along with lipid digestion product.
These help the lipid to absorb across the cell membrane