Some of the factors may not be easily modifiable.
Stabilization
strategies
Some
of the factors may not be easily modifiable. For example, drug’s pKa, 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.
Related Topics
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