Modified drug release from inert matrix tablets prepared from formulations of identical composition but different organisations.
This paper develops for the first time a concept to modify the release rate of a fixed formulation by changing only the organisation of the mix used to prepare the tablets (ordered mixing). To estimate the influence of the organisation of binary mixes, several mixes of ethylcellulose and niflumic acid of the same composition but different organisation were compacted. The tablet surfaces were examined by energy dispersive X-ray microanalysis before the release experiments. Finally, the cross-sections of the remaining matrix were examined by scanning electronic microscopy. Excipient-excipient and excipient-drug interactions are the major factors influencing the drug release rate from the tablets. In the case of interacting materials, the initial release behaviour depends on the tablet surface presented to the dissolution media. The dissolution properties of the tablets are governed by the percolating material. When the inert excipient is percolating, the release rate increases linearly with the excipient/drug size ratio, whereas when the drug is the only material percolating through the system, its release rate is independent of the size ratio. When both materials are percolating through the system, the release rate is independent of the component particle sizes.
Barra
J
J
School of Pharmacy, University of Geneva, Quai Ernest-Ansermet 30, 1211, Geneva, Switzerland. jerome.barra@firmenich.com
Falson-Rieg
F
F
Doelker
E
E
D002482:Cellulose / Q000031:analogs & derivatives; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D004339:Drug Compounding / Q000379:methods*; D004577:Electron Probe Microanalysis; D008855:Microscopy, Electron, Scanning; D009544:Niflumic Acid / Q000008:administration & dosage; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D016062:Porosity; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D014783:Viscosity
D016861:Cyclooxygenase Inhibitors; D014677:Pharmaceutical Vehicles; D013607:Tablets; D009544:Niflumic Acid; C013517:ethyl cellulose; D002482:Cellulose