Abstract
As a result of its higher molecular mobility, the surface of an amorphous drug can grow crystals much more rapidly than the bulk, causing poor stability and slow dissolution of drug products. We show that a nanocoating of chitosan (a pharmaceutically acceptable polymer) can be deposited on the surface of amorphous indomethacin by electrostatic deposition, leading to significant improvement of physical stability, wetting by aqueous media, dissolution rate, powder flow, and tabletability. The coating condition was chosen so that the positively charged polymer deposits on the negatively charged drug. Chitosan coating is superior to gelatin coating with respect to stability against crystallization and agglomeration of coated particles.
Highlights
An active pharmaceutical ingredient can exist in many solid forms, both crystalline and amorphous
Recent work has shown that molecular mobility can be extremely high on the free surface of amorphous drugs, and this leads to rapid crystal growth on the surface, while bulk crystal growth is relatively slow.[2−4] These results suggest that preventing surface crystallization is an efficient way to improve the stability of amorphous drugs
This work has shown that the surface crystallization of amorphous indomethacin can be inhibited by a nanocoating of a pharmaceutically acceptable polyelectrolyte, chitosan
Summary
An active pharmaceutical ingredient can exist in many solid forms, both crystalline and amorphous. Amorphous formulations have attracted recent attention as a general method to improve the solubility and dissolution rate of poorly soluble drugs.[1] A key issue in this effort is the stability against crystallization, since amorphous drugs tend to crystallize over time, and crystallization would eliminate their advantages. Recent work has shown that molecular mobility can be extremely high on the free surface of amorphous drugs, and this leads to rapid crystal growth on the surface, while bulk crystal growth is relatively slow.[2−4] These results suggest that preventing surface crystallization is an efficient way to improve the stability of amorphous drugs. For indomethacin (IMC, Scheme 1, a weak acid with pKa = 4.5), coating was performed at pH = 5, at which the drug is negatively charged so that the polycation polydiallyldimethylammonium chloride (PDDA) can deposit on it.
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