Pharmaceutics and Pharmaceutical Technology: Formulation and Bioavailability
The central idea
A dosage form exists to deliver a drug reproducibly. Bioavailability depends on dissolution and permeability, which is why the Biopharmaceutics Classification System matters: Class I high solubility/high permeability, Class II low solubility/high permeability (dissolution-rate limited, so particle-size reduction or amorphous forms help), Class III high solubility/low permeability (permeability limited), Class IV low/low (formulation is difficult).
Formulation tools
Know excipient roles: diluents, binders, disintegrants, glidants, lubricants, coatings, preservatives, antioxidants, buffers and suspending agents. Salts and polymorphs change solubility and stability; the amorphous form has higher apparent solubility but is physically less stable and may crystallise on storage.
Sustained-release designs slow release through matrix or membrane control; enteric coatings resist gastric acid and exist to protect acid-labile drugs or the stomach. Suspensions require shaking and depend on controlled flocculation; emulsions are o/w or w/o and characterised by HLB.
Stability and shelf life
Degradation is usually hydrolysis, oxidation or photolysis. The shelf life is generally the time to 90% potency (t90), and the Arrhenius relationship indicates that reaction rates roughly double per 10 °C rise - the reason refrigeration extends expiry.
Traps
Assuming smaller particles are always better (agglomeration, poor flow, instability); forgetting that a product can be chemically stable but physically unstable; ignoring the effect of food and first-pass metabolism on bioavailability.
Worked example
A Class II weak-acid drug formulated as the sodium salt dissolves faster than the free acid; the salt form raises pH locally and improves dissolution rate, so the salt and the acid are not automatically bioequivalent without data.