Chiral purity physicochemical

Numerous methods are required to characterize drug substances and drug products (Chapter 10). Specifications may include description identification assay (of composite sample) tests for organic synthetic process impurities, inorganic impurities, degradation products, residual solvents, and container extractables tests of various physicochemical properties, chiral purity, water content, content uniformity, and antioxidant and antimicrobial preservative content microbial tests dissolution/disintegration tests hardness/friability tests and tests for particle size and polymorphic form. Some of these tests may be precluded, or additional tests may be added as dictated by the chemistry of the pharmaceutical or the dosage form. 

Additional preformulation and physicochemical characterization of the candidate compound are performed and stress stability studies may be initiated. Ideally, the optimal solid-state (polymorphic) and chemical (salt) form of the molecule are identified as part of clinical candidate selection. Selection of the most stable and bio-available chemical and physical forms will expedite subsequent development. The methods for testing the drug substance are refined and additional methods may be developed, including tests for physical, chemical, and chiral purity. Analytical characterization becomes extremely critical where significant formulation intervention is required such as amorphous formulations for BCS 2/4 compounds, inhalation products, or highly concentrated formulations for monoclonal antibodies. 

As already described, PLA can be manufactured to give a wide range of properties because of the chiral nature of lactide. The mechanical characteristics of PLA are known to depend on the choice and distribution of stereoisomers within the polymer chains. High-purity l- and D-lactide form stereoregular isotactic PLLA and PDLA, respectively, with equivalent physicochemical and mechanical properties. These are semicrystalline polymers with a high around 175-180°C and a Tg in the 60-70°C range. The racemic d,l-lactide and mc o-lactide, on the other hand, form atactic POLL A and mcio-poly(lactide), which are amorphous materials [30-32]. 

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