Novel polyvinylpyrrolidones to improve delivery of poorly water-soluble drugs: from design to synthesis and evaluation.
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.
School of Pharmacy, University of Reading , Whiteknights, P.O. Box 226, Reading, RG6 6AP, United Kingdom.
Anna I
AI
Niemczyk
Adrian C
AC
Williams
Clare F
CF
Rawlinson-Malone
Wayne
W
Hayes
Barnaby W
BW
Greenland
David
D
Chappell
Olga
O
Khutoryanskaya
Peter
P
Timmins
D004337:Drug Carriers / Q000737:chemistry*; D006860:Hydrogen Bonding; D007052:Ibuprofen / Q000737:chemistry; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry*
D004337:Drug Carriers; D014867:Water; D011205:Povidone; D007052:Ibuprofen