Lawrence John Penkler

Diclofenac — ß — Cyclodextrin Inclusion in Solution Proton Magnetic Resonance and Molecular Modelling Studies

The nature of the inclusion complex of the NSAID [2-[(2, 6-dichlorophenyl) amino]phenyl]acetic acid (diclofenac) with β-cyclodextrin and 2-hydroxypropyl-s-cyclodextrin was studied by selected ID and 2D NMR experiments and by molecular modelling studies using Hyperchem® software. The results indicate that simultaneous inclusion of both rings occurs even at low drug/CD ratios giving rise to multiple equilibria in solution (two isomeric 1:1 complexes and a 1:2 complex). Continuous variation plots are supportive of 1:1 stoichiometry indicating that isomeric 1:1 complexes predominate in the range of concentrations studied.

Enhanced Pharmacokinetic Properties of Oral and Parenteral Diclofenac-Cyclodextrin Delivery Systems

The application of beta cyclodextrins to enhance the oral and parenteral delivery of the extensively used NSAID diclofenac sodium is described. Tablets containing microcrystalline 1:1 diclofenac sodium/beta-cyclodextrin complex prepared by kneading in a one pot ROTO granulator were formulated with an alkali agent. In a. single dose cross-over study (n=6) the test product yielded mean Tmax after 20 min compared with 40 min for the reference commercial non-enteric coated tablets, and showed more complete absorption. A stable 75mg/3mL aqueous solution of diclofenac sodium/2-hydroxypropyl-beta-cyclodextrin (1:2 mol/mol) was administered via im and iv injection to 6 volunteers. Relative to the commercial im reference product, the test showed significantly enhanced im and interesting iv pharmacokinetics.