AI Article Synopsis
- A CFD model was created to predict how metformin, a diabetes medication, is released from a specific type of extended-release tablet made with HPMC, considering various properties like the drug's characteristics and tablet shape.
- The geometry of a new high-dose (1000 mg) tablet was designed using a method focusing on surface area to volume ratio, which helped in achieving consistent drug release rates across different tablet sizes.
- The simulated drug release matched well with actual experimental results, and the developed absorption model effectively predicted clinical exposure, leading to the successful completion of a bioequivalence study confirming predicted outcomes.
Article Abstract
A computational fluid dynamic (CFD) model was developed to predict metformin release from a hydroxypropylmethylcellulose (HPMC) matrix-based extended-release formulation that took into consideration the physical and chemical properties of the drug substance, composition, as well as size and shape of the tablet. New high dose strength (1000 mg) tablet geometry was selected based on the surface area/volume (SA/V) approach advocated by Lapidus/Lordi/Reynold to obtain the desired equivalent metformin release kinetics. Maintaining a similar SA/V ratio across all extended-release metformin hydrochloride (Met XR) tablet strengths that had different geometries provided similar simulations of dissolution behavior. Experimental dissolution profiles of three lots of high-strength tablets agreed with the simulated release kinetics. Additionally, a pharmacokinetic absorption model was developed using GastroPlus™ software and known physicochemical, pharmacokinetic, and in vitro dissolution properties of metformin to predict the clinical exposure of the new high strength (1000 mg) tablet prior to conducting a human clinical bioequivalence study. In vitro metformin release kinetics were utilized in the absorption model to predict exposures in humans for new 1000-mg Met XR tablets, and the absorption model correctly projected equivalent in vivo exposure across all dose strengths. A clinical bioequivalence study was pursued based on the combined modeling results and demonstrated equivalent exposure as predicted by the simulations.
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| http://dx.doi.org/10.1208/s12249-015-0423-9 | DOI Listing |
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