Abstract
A large number of the new pharmaceutical small molecules under development today are found to have poor water solubility. This in turn may lead to low bioavailability, which can have a significant impact on the development of the compound. Compounds with low bioavailability pose a greater challenge in early preclinical work involving animal studies, where obtaining maximum exposure is the primary goal especially in toxicology studies designed to establish the safe dose. From the standpoint of maximizing exposure, the amorphous phase is of great interest as pharmaceutical materials since it is the most metastable state and as such offers the potential of higher solubility and better bioavailability. However, the amorphous approach is not actively pursued in preclinical work owing to the tendency of the amorphous phase to crystallize thereby neutralizing the solubility advantage. This review focuses on (i) methods to generate the amorphous phase, (ii) methods to estimate the degree of crystallinity of the amorphous phase, (iii) methods to predict the stability of the amorphous phase against crystallization, and (iv) choice of polymers carrier and formulation of the amorphous phase for preclinical studies.
Keywords: Amorphous pharmaceuticals, crystallization, preclinical, solid dispersions
Current Bioactive Compounds
Title: Amorphous Active Pharmaceutical Ingredients in Preclinical Studies: Preparation, Characterization, and Formulation
Volume: 4 Issue: 4
Author(s): Karthik Nagapudi and Janan Jona
Affiliation:
Keywords: Amorphous pharmaceuticals, crystallization, preclinical, solid dispersions
Abstract: A large number of the new pharmaceutical small molecules under development today are found to have poor water solubility. This in turn may lead to low bioavailability, which can have a significant impact on the development of the compound. Compounds with low bioavailability pose a greater challenge in early preclinical work involving animal studies, where obtaining maximum exposure is the primary goal especially in toxicology studies designed to establish the safe dose. From the standpoint of maximizing exposure, the amorphous phase is of great interest as pharmaceutical materials since it is the most metastable state and as such offers the potential of higher solubility and better bioavailability. However, the amorphous approach is not actively pursued in preclinical work owing to the tendency of the amorphous phase to crystallize thereby neutralizing the solubility advantage. This review focuses on (i) methods to generate the amorphous phase, (ii) methods to estimate the degree of crystallinity of the amorphous phase, (iii) methods to predict the stability of the amorphous phase against crystallization, and (iv) choice of polymers carrier and formulation of the amorphous phase for preclinical studies.
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Cite this article as:
Nagapudi Karthik and Jona Janan, Amorphous Active Pharmaceutical Ingredients in Preclinical Studies: Preparation, Characterization, and Formulation, Current Bioactive Compounds 2008; 4 (4) . https://dx.doi.org/10.2174/157340708786847852
DOI https://dx.doi.org/10.2174/157340708786847852 |
Print ISSN 1573-4072 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6646 |
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