RESUMEN
The aim of this work was to formulate glimepiride (class II drug) which is characterized by low solubility and high permeability as nanostructured particles using a cryogenic technique with an aid of water-soluble polymer to improve its aqueous solubility and hence its bioavailability. 27 formula of glimepiride nano size particles were prepared by a spray freezing into cryogenic liquid (SCFL) using poly vinyl pyrrolidone K-30 (PVP K-30); that three drug polymer ratio (1:1, 1:2, and 1:3), with three different volumes of feeding solution (50, 100, 150 mL), at three flow rates (10, 20, and 30 mL/min). The prepared formulations were evaluated for production yield, particle size, zeta potential, drug content, release rate, in vivo hypoglycemic activity, and bioavailability. All prepared formulations showed high production yield and drug content ranged between 91.1 ± 3.4% and 94.3 ± 1.8% and 95.1 ± 2.8% and 97.1 ± 2.5%, respectively. The mean particles size was ranged between 280 ± 62 nm and 520 ± 30 nm. The results of in vitro release study revealed significant enhancement in the solubility of prepared formulations compared with the pure drug. It was found that optimal formula showed a significant reduction in blood glucose levels in diabetic rats, and 1.79-fold enhancements in oral bioavailability compared with market tablets. Nanoparticle prepared by SCFL method is an encouraging formula for improving the solubility and the bioavailability of glimepiride.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Compuestos de Sulfonilurea/administración & dosificación , Compuestos de Sulfonilurea/farmacología , Animales , Área Bajo la Curva , Glucemia , Portadores de Fármacos/química , Liberación de Fármacos , Congelación , Hipoglucemiantes/farmacocinética , Masculino , Tasa de Depuración Metabólica , Nanopartículas/química , Tamaño de la Partícula , Povidona/química , Ratas , Ratas Wistar , Solubilidad , Compuestos de Sulfonilurea/farmacocinética , Propiedades de Superficie , Comprimidos , Tecnología FarmacéuticaRESUMEN
INTRODUCTION: Controlling the drug release from the dosage form at a definite rate is the main challenge for a successful oral controlled-release drug delivery system. In this study, mini-tablets (MTs) and lipid/polymer nanoparticles (LPNs) of lipid polymer and chitosan in different ratios were designed to encapsulate and control the release time of Amoxicillin (AMX). METHODS: Physical characteristics and in vitro release profiles of both MT and LPN formulations were studied. Antimicrobial activity and oral pharmacokinetics of the optimum MT and LPN formulations in comparison to market tablet were studied in rats. RESULTS: All designed formulations of AMX as MTs and LPNs showed accepted characteristics. MT-6 (Compritol/Chitosan 1:1) showed the greatest retardation among all prepared minitablet preparations, releasing about 79.5% of AMX over 8 h. In contrast, LPN-11 (AMX: Cr 1:3/Chitosan 1 mg/mL) had the slowest drug release, revealing the sustained release of 80.9% within 8 h. The MIC of both optimized tablet formula (MT-6) and LPNs formula (LPN-11) was around two-fold lower than the control against H. pylori. The Cmax of MT-6 and LPN11 were non significantly different compared with the marketed AMX product. While the bioavailability experiment proved that the relative bioavailability of the AMX was 1.85 and 1.8 after the oral use of LPN11 and MT-6, respectively, compared to the market tablet. CONCLUSION: The results verified that both controlled-release mini-tablets and lipid/polymer nanoparticles can be used for sustaining the release and hence improve the bioavailability of amoxicillin.