Stabilization strategies

Stabilization strategies

Some of the factors may not be easily modifiable. For example, drug’s pK_a, salt/counterion, propensity for disproportionation (i.e., separation of the counterion from the free base or the free acid form of the drug) in the dos-age form, crystalline form, concentration of the drug in the dosage form, and intrinsic solubility are determined by the chemistry and clinical needs of the compound.

Other external factors, such as temperature, humidity, pH, light, and additives that may act as reaction catalysts or quenchers, may be readily controlled to achieve desired drug product’s shelf life stability.

Drug product stabilization is a constantly evolving field with new informa-tion and insights, helping stabilize a wide variety of molecules. For example,

·           Wet granulation manufacturing process for solid dosage forms results in better distribution of the stabilizing agent within the powder matrix than the dry granulation process. Thus, improved product stabiliza-tion can be obtained with the wet granulation process.

·           Polyionic surfactants can promote disproportionation of the salt form of a drug in the dosage form to its free acid or free base form, which is generally more reactive than the salt form. Stabilization strategies in such cases consist of avoiding highly ionized excipient or creating a microenvironment in the drug product that disfavors disproportion-ation of the drug.

·           Reduction of particle size of the drug, though good for improving the dissolution rate and bioavailability of the drug from the dosage form, may be counterproductive to solid-state reactions that are limited by the surface area of the compound. Use of larger-particle-size drug or physical separation of the drug from the reactive excipient in the dos-age form is an effective strategy in such cases.

Identifying degradation mechanisms/pathways, delineating reaction kinet-ics, and adopting stabilization strategies that can support drug product stability for clinical studies and shelf life during commercial manufacture are the key roles of pharmaceutical scientists in modern drug development. The science of drug product stabilization keeps evolving with the discovery of ever-newer chemistries, with newer molecules in the discovery pipeline.