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G A McClelland

Publications and source records attributed to G A McClelland.

5 recordsLinked to original sources
PubMed1991

The solubility-modulated osmotic pump: in vitro/in vivo release of diltiazem hydrochloride.

A generalized method was investigated for conversion of controlled-porosity osmotic pump release profiles from first-order to zero-order kinetics using diltiazem.HCl as a model drug. Diltiazem.HCl has an aqueous solubility greater than 590 mg/ml (37 degrees C) and was released from controlled-porosity osmotic pump devices with first-order kinetics. This high solubility was markedly reduced (155 mg/ml; 37 degrees C) in the presence of NaCl (1 M). Based on theory for osmotically actuated drug release, this reduced solubility would be expected to result in a zero-order release profile of greater than 80% of an initial diltiazem.HCl load. Devices were prepared with cores that contained diltiazem.HCl and sufficient NaCl granules coated with a microporous cellulose acetate butyrate 381-20 film to maintain a 1 M NaCl concentration within the drug compartment over a 16-hr period. This resulted in release of approximately 75% of the initial diltiazem.HCl load with zero-order kinetics over a 14- to 16-hr period. The in vivo performance of these devices in beagle dogs was analyzed. The in vivo percentage diltiazem absorbed profiles were superimposable with the in vitro release profile. These results suggest that diltiazem release and absorption from the solubility modulated osmotic pump occur throughout the GI tract in a fashion predictable from in vitro dissolution data.

Animals↗
PubMed1991

Enhancement of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor efficacy through administration of a controlled-porosity osmotic pump dosage form.

An extended-release osmotic dosage form was designed for gastrointestinal delivery of the water-soluble tromethamine salt of the beta-hydroxyacid form of simvastatin, a potent HMG-CoA reductase inhibitor and cholesterol lowering agent. The cholesterol lowering efficacy and systemic plasma drug levels resulting from peroral administration of this dosage form, relative to a powder-filled capsule oral bolus, were evaluated in dogs. A twofold improvement in cholesterol lowering efficacy was realized with the controlled-release dosage form that was accompanied by a drug AUC and Cmax that were 67 and 16%, respectively, of those achieved with the bolus dosage form. These results suggest that extended-release dosage forms have the potential for a dose-sparing advantage in the administration of HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia.

Animals↗