In vivo evaluation of an indomethacin monolithic, extended zero-order release hard-gelatin capsule formulation based on saturated polyglycolysed glycerides

Article Article scientifique Article In vivo evaluation of an indomethacin monolithic, extended zero-order release hard-gelatin capsule formulation based on saturated polyglycolysed glycerides eng 1995-12 author Vial-Bernasconi Anne-Claire Thérèse 30826 author Buri Pierre 24841 Administration de la faculté des sciences (SIAD) author Doelker Eric 25151 Administration de la faculté des sciences (SIAD) author Beyssac E. author Duchaix G. author Aiache J.-M. 307-313 10.1016/0031-6865(95)00036-4 8765697 0031-6865 The sustained release properties of an indomethacin hard-gelatin capsule formulated with saturated polyglycolysed glycerides (Gelucire®) were demonstrated in vivo. Indomethacin was selected as a model drug with very poor solubility in water and acidic media. It is known to exhibit high intersubject variability because of enterohepatic circulation. The formulation, which in vitro showed an erosion-controlled release, was compared in six human volunteers in the fed state by using a randomized cross-over design, to a standard multiple-unit diffusion-controlled pellet capsule. Close action period values (time duration with plasma levels higher than 0.5 μg/ml) were found for the test and the reference formulation (5.2 and 5.7 h). The time to reach peak tmax appeared slightly shorter for the test preparation (1.75 h) than for the reference formulation (2.67 h), but the difference was not statistically significant because of the high intersubject variability (non-parametric Wilcoxon matched pair test). Again, due to the small number of subjects entered in the study (insufficient for a real bioequivalence study) equivalence could not be accepted in terms of extent and rate of absorption based on the decision procedures involving the 90% confidence interval and the two one-sided t-tests. The mean maximum plasma concentrations Cmax were 3.35 and 2.82 μg/ml for the test and the reference formulation respectively, with the corresponding values of the area under the plasma concentration-time curve AUC amounting to 10.14 and 11.38 μg h/ml. However, a simulation on 24 subjects (3 repetitions of the same data) would lead to bioequivalence of the two preparations. As for other corrosion-controlled forms, drug release from the proposed Gelucire® formulation was very sensitive to hydrodynamic conditions, leading to poor in vitro-in vivo correlation, when comparison is made with a reference formulation characterized by a diffusion-controlled release. Finally, it was concluded that erosion-controlled release formulations are especially suitable for drugs, such as indomethacin, that have low solubility in water or acidic media. More generally, sustained release hard gelatin capsules with thermosetting excipients is very versatile and their preparation is very straightforward. Indomethacin Pharmacokinetics, zero-order Bioavailability Hard-gelatin capsule Erosion-controlled release Saturated polyglycolysed glycerides Dewey 615 31 Section des sciences pharmaceutiques 17 false Pharmaceutica Acta Helvetiae 70 4 598b93e8-af84-44f0-a12a-e29f508053b2 Article (Published version) Restricted Vial-Bernasconi_PAH_199570307.pdf 710049 application/pdf cf29149c6134ca4c754ed2cb068a6a47bd940c7d63652a51921c23e26571283f restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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In vivo evaluation of an indomethacin monolithic, extended zero-order release hard-gelatin capsule formulation based on saturated polyglycolysed glycerides	Pharmaceutica Acta Helvetiae			1995	77	0

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Vial-Bernasconi, Anne-Claire Thérèse