Excipients

In the past three decades, the pharmaceutical industry has seen
the development of drugs that actually cure disease rather
than just offer symptomatic relief. During these years, the
concepts of improving efficacy and good manufacturing practices
(GMPs) have grown in importance. In addition, toward
the end of the last quarter of the previous century, many new
concepts and terms had come into common usage. For example,
the concept that a dosage form must act to release the active
ingredient has become generally accepted.Words like disintegration,
dissolution, and bioavailability also have gained
prominence and meaning.Accompanying these terms and concepts
was the realization that inactive ingredients frequently
are critical to ensure storage stability, safety, and efficacy of drug
dosage forms. The transition from excipients being perceived
as inactive, inert ingredients to the present status of pharmaceutical

Global research in pharmaceutical sciences will acquire
new dimensions in the post-GATT (General Agreement
in Trade and Tariff) era. The pharmaceutical industry
currently is focused on the identification and
development of novel leads from areas such as biotechnology,
combinatorial chemistry,molecular modeling, and genetic engineering.
The leads coming from these varied sources will require
specialized formulation techniques and ingredients. At
the same time, the process of discovering new drugs is a costly
proposition and requires input from the basic as well as applied
sciences. Research organizations that do not have adequate expertise
or vision tend to fall out rapidly. The alternative approach
for such organizations would be to develop new dosage
forms or formulations using novel excipients for the existing
drugs that offer distinct benefits over the conventional formulations.

Abstract: The purpose of this study was to evaluate the mechanisms of aggregate formation and excipient stabilization in freeze-dried formulations of a recombinant humanized monoclonal antibody. Protein degradation was measured using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) and native size exclusion chromatography, and protein structure was studied using Fourier transform-infrared spectrometry and circular dichroism. The results showed that protein aggregates present following reconstitution were composed of native antibody structure and a reduced amount of free thiol when compared to protein monomer, which implied that intermolecular disulfides were involved in the aggregation mechanism. An excipient-free formulation resulted in reversible solid-state protein structural alteration and increased aggregation during storage.

IPEC-Americas has just completed a major update to its significant change guideline to address current issues in the manufacture.
In the October 2000 issue of this magazine, I described the recently issued International Pharmaceutical Excipients Council of the Americas (IPEC-Americas) Significant Change Guide for Bulk Pharmaceutical Excipients.Now, IPEC-Americas has completed a major update to the guideline to address current concerns about bovine spongiform encephalopathy, genetically modified organisms, and allergens. The updated guide also contains a new section to assist manufacturers in developing an impurity profile. of excipient ingredients and to assist manufacturers in developing an impurity profile.




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