39 - Chemical and Physicochemical Solutions to Formulation Problems

Abstract

Medicinal chemists aim to discover new lead compounds and optimize them to highly potent, selective, and nontoxic new drug candidates. However, the selected drug candidates can still present some drawbacks of physicochemical nature, or drawbacks that might affect the patient's compliance. To render the compound marketable, the pharmacists must then invent an adequate pharmaceutical formulation, stable on keeping, and perfectly adapted to its clinical use. In leaving this task to the formulation pharmacists, the chemists are not always aware of their own role in the formulation phase and the final presentation of a new drug. The shelf-life of an organic chemical is the time taken for its pharmacological activity to fall by an acceptable amount. The shelf-life of an organic chemical is the time taken for its pharmacological activity to fall by an acceptable amount. While this cannot be universally defined, about 10% decomposition may be considered acceptable, unless the decomposition products are toxic. Among possible decomposition paths, the following are the most frequent: hydrolysis, oxidation, photochemical degradations, racemization, thermal decomposition, chemical interactions, and microbial degradations. Usually, selected pharmaceutical prevention procedures and manufacturing practices can overcome decomposition problems. However, it can happen that chemical derivatizations are needed to achieve satisfactory drug formulations.