Priprava i vrednovanje šumećih plutajućih tableta tizanidin hidroklorida

Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility throughout the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (3440 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h.Tizanidin hidroklorid je prokinetički agens za peroralnu primjenu koji olakšava ili obnavlja mobilnost kroz gastrointestinalni trakt. Cilj rada bio je razvoj šumećih plutajućih matriksnih tableta tizanidin hidroklorida za produljenje zadržavanja u želucu u svrhu poboljšanja niske bioraspoloživosti (3440 %) i produljenja vremena poluživota (4,2 h). Tablete su pripravljene metodom izravne kompresije, koristeći hidroksipropil metilcelulozu različite viskoznosti (HPMCK4M, K15M i K100M). Određeni su različiti fizikalni parametri. Oslobađanje ljekovite tvari in vitro bilo je polagano tijekom 12 sati, a tablete su imale svojstvo plutanja. Prema DSC ispitivanja nema interakcije s pomoćnim tvarima. Kinetička ispitivanja pokazuju da oslobađanje iz svih pripravaka slijedi Higuchijev model, kinetiku prvog reda i ne-Fickov zakon. Na temelju faktora sličnosti (f2) (74,2), oslobađanja ljekovite tvari nakon 2, 6 i 8 h, te vremena poluživota t50 (5,4 h) izabrana je optimirana formulacija (F9) i upotrebljena u radiografičkim ispitivanjima koja uključuju BaSO4. In vivo ispitivanja rendgenskim zrakama na dobrovoljcima pokazala su da je srednje vrijeme zadržavanja u želucu bilo 6,2 ± 0,2 h