Impact of Polymer Conformation on the Crystal Growth Inhibition of a Poorly Water-Soluble Drug in Aqueous Solution
Year: 2014
Type: article
Abstract: Poor aqueous solubility is a major hindrance to oral delivery of many emerging drugs. Supersaturated drug solutions can improve passive absorption across the gastrointestinal tract membrane as long as crystallization can be inhibited, enhancing the delivery of such poorly soluble therapeutics. Polymers can inhibit crystallization and prolong supersaturation; therefore, it is desirable to understand the attributes which render a polymer effective. In this study, the conformation of a polymer adsorbed to a crystal surface and its impact on crystal growth inhibition were investigated. The crystal growth rate of a poorly soluble pharmaceutical compound, felodipine, was measured in the presence of hydroxypropyl methylcellulose acetate succinate (HPMCAS) at two different pH conditions: pH 3 and pH 6.8. HPMCAS was found to be a less effective growth rate inhibitor at pH 3, below its pKa. It was expected that the ionization state of HPMCAS would most likely influence its conformation at the solid-liquid interface. Further investigation with atomic force microscopy (AFM) revealed significant differences in the conformation of HPMCAS adsorbed to felodipine at the two pH conditions. At pH 3, HPMCAS formed coiled globules on the surface, whereas at pH 6.8, HPMCAS adsorbed more uniformly. Thus, it appeared that the reduced effectiveness of HPMCAS at pH 3 was directly related to its conformation. The globule formation leaves many felodipine growth sites open and available for growth units to attach, rendering the polymer less effective as a growth rate inhibitor.
Source: Langmuir
DOI: 10.1021/la503644m
Institution: Purdue University West Lafayette
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: G138300334, G2830875348, G2913527522, Engineering Research Center (ERC) for Structured Organic Composites for Pharmaceutical, Nutraceutical, and Agrochemical Applications(C-SOC), G3540675822, G4176647331, SBIR Phase II: Nanoscale Ultrafast Dynamic Mechanical Analysis (nu-DMA), Development of a new Imaging Platform for Pharmaceutical and Biomedical applicati
OpenAlex ID: W2071871708