Novel Polyvinylpyrrolidones To Improve Delivery of Poorly Water-Soluble Drugs: From Design to Synthesis and Evaluation
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- 作者：Anna I. Niemczyk ; Adrian C. Williams ; Clare F. Rawlinson-Malone ; Wayne Hayes ; Barnaby W. Greenland ; David Chappell ; Olga Khutoryanskaya ; Peter Timmins
- 刊名：Molecular Pharmaceutics
- 出版年：2012
- 出版时间：August 6, 2012
- 年：2012
- 卷：9
- 期：8
- 页码：2237-2247
- 全文大小：511K
- 年卷期：v.9,no.8(August 6, 2012)
- ISSN：1543-8392
文摘
Polyvinylpyrrolidone is widely used in tablet formulations with the linear form acting as a wetting agent and disintegrant, whereas the cross-linked form is a superdisintegrant. We have previously reported that simply mixing the commercial cross-linked polymer with ibuprofen disrupted drug crystallinity with consequent improvements in drug dissolution behavior. In this study, we have designed and synthesized novel cross-linking agents containing a range of oligoether moieties that have then been polymerized with vinylpyrrolidone to generate a suite of novel excipients with enhanced hydrogen-bonding capabilities. The polymers have a porous surface and swell in the most common solvents and in water, properties that suggest their value as disintegrants. The polymers were evaluated in simple physical mixtures with ibuprofen as a model poorly water-soluble drug. The results show that the novel PVPs induce the drug to become 鈥淴-ray amorphous鈥? which increased dissolution to a greater extent than that seen with commercial cross-linked PVP. The polymers stabilize the amorphous drug with no evidence for recrystallization seen after 20 weeks of storage.