Novel polyvinylpyrrolidones to improve delivery of poorly-water soluble drugs; from design to synthesis and evaluation
Niemczyk, A. I., Williams, A. C., Rawlinson-Malone, C. F., Hayes, W., Greenland, B., Chappell, D. and Khutoryanskaya, O. (2012) Novel polyvinylpyrrolidones to improve delivery of poorly-water soluble drugs; from design to synthesis and evaluation. Molecular Pharmaceutics, 9 (8). pp. 2237-2247. ISSN 1543-8392
To link to this article DOI: 10.1021/mp300079x
Polyvinylpyrrolidone is a widely used in tablet formulations with the linear form acting as a wetting agent and disintegrant whereas the cross-linked form is a super-disintegrant. 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 which have then be polymerized with vinylpyrrolidone to generate a suite of novel excipients with enhanced hydrogen-bonding capabilities. The polymers have a porous surface and swell in most common solvents and in water; properties which 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 storage.