Characterization of binary mixtures consisting of cross-linked high amylose starch and hydroxypropylmethylcellulose used in the preparation of controlled release tablets.
Cross-linked amylose starch (CLA), hydroxypropylmethylcellulose (HPMC), and HPMC/CLA matrices were prepared by direct compression. HPMC was used to slow down the enzymatic degradation of CLA matrices. CLA was either granulated alone and mixed with HPMC or cogranulated with the latter. Compaction characteristics of the powder, hydration and mechanical properties of the resulting matrices, as well as the release profiles of three model drugs were investigated. The results showed that wet granulation of CLA in the presence of 10% HPMC improved significantly the flow properties of the powder without compromising its compactibility. Both CLA and HPMC deformed mainly by plastic flow (yield pressures are 75 and 124 MPa, respectively), but CLA exhibited a stronger elastic component (elastic recoveries are 18.4 and 11.5%, respectively). The values of yield pressure increased linearly with the concentration of HPMC. The addition of HPMC to CLA slightly decreased the resistance to consolidation but the crushing force of the final compacts was found to be proportional to the HPMC concentration. Mechanical studies on swollen matrices revealed that CLA formed a stronger gel than HPMC or CLA/HPMC mixture, and swelling and erosion of the tablets increased with HPMC content and incubation time. The in vitro release kinetics of three model drugs (pseudeoephedrine sulfate, sodium diclofenac, and prednisone) showed a clear effect of drug solubility and presence of alpha-amylase in the dissolution medium on the release rate. The addition of HPMC to CLA protected the tablets against alpha-amylase hydrolysis and reduced the release rate of prednisone and sodium diclofenac. The release of pseudoephedrine sulfate was fast and independent of HPMC and occurred mainly by diffusion.
Faculty of Pharmacy, University of Montreal, Montréal, Québec, Canada.
Miloud
M
Rahmouni
Vincent
V
Lenaerts
Danielle
D
Massuelle
Eric
E
Doelker
Marc
M
Johnson
Jean-Christophe
JC
Leroux
D000688:Amylose / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D019245:Compressive Strength; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000379:methods; D004798:Enzymes / Q000378:metabolism; D005782:Gels / Q000737:chemistry; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000493:pharmacokinetics; D010539:Permeability; D012995:Solubility; D013607:Tablets / Q000737:chemistry* / Q000493:pharmacokinetics
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004798:Enzymes; D005782:Gels; D013607:Tablets; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D000688:Amylose