Novel polyvinylpyrrolidones to improve delivery of poorly water-soluble drugs: from design to synthesis and evaluation

Mol Pharm. 2012 Aug 6;9(8):2237-47. doi: 10.1021/mp300079x. Epub 2012 Jul 13.

Abstract

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 "X-ray amorphous", 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Carriers / chemistry*
  • Hydrogen Bonding
  • Ibuprofen / chemistry
  • Povidone / chemistry*
  • Solubility
  • Water / chemistry*

Substances

  • Drug Carriers
  • Water
  • Povidone
  • Ibuprofen