Effects of additives on dissolution and growth of drug crystals
Abstract
The purpose of the present study was to investigate how polymeric additives affect the dissolution and growth of drug crystals. The etching patterns of the acetaminophen (010) face in the presence of polymeric additives may be different from those in the absence of polymeric additives, and the difference can be used to detect the molecular interactions between polymeric additives and acetaminophen on a crystal surface. For those adsorbed polymers that can form hydrogen bonds with acetaminophen on crystal surface, the etching pattern along a-axis will be affected or even removed depending on the strength of the interactions. The inhibitory effects of polymeric additives on nucleation and growth are consistent with the effects on the etching patterns in that the more the etching patterns along a-axis are affected, the more the inhibitory effects. The morphology change in the presence of PVP shows that there exist strong interactions on crystal surface along the direction between b-axis and c-axis, which is consistent with the observation that the etching pattern along c-axis has been affected in the presence of PVP. The significance of the polymer adsorption has been further confirmed by some related information including the solubility and the intrinsic dissolution rate of acetaminophen in polymer solutions, the viscosity of polymer solutions as well as the polymer mobility checked by dielectric analysis. To understand why different polymeric additives have different effects on dissolution and crystallization, Dynamic Adsorption Model and Equilibrium Adsorption Model have been proposed.
Degree
Ph.D.
Advisors
Park, Purdue University.
Subject Area
Pharmaceuticals|Pharmacology
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