GLIMEPIRIDE FAST DISINTEGRATING TABLETS: FORMULATION, EVALUATION AND IN-VIVO DISINTEGRATION AND DYNAMIC STUDIES

Objective: The main objective of the research was to formulate directly compressible fast disintegrating tablets of glimepiride by using different super disintegrants such as crospovidone, croscarmellose sodium, sodium starch glycolate and L-HPC in various concentrations.Methods: The prepared tablets were evaluated for various tablet properties like weight variation, thickness, hardness, friability, taste, drug content, in vitro and in vivo disintegration time, and in vitro drug release, in vivo dynamic studies. Other parameters such as wetting time, water absorption ratio, and drug-excipient compatibility were also evaluated.Results: The disintegration time of the optimized fast disintegrating tablet formulation was observed to be 12 s in vitro and 19.80 s in vivo. The correlation was observed between disintegration time and ‘R' for each of the four super disintegrants at the concentrations studied. Considering the ‘R' values and disintegration time, croscarmellose sodium was significantly superior compared to the other super disintegrants tested. Drug release was faster from formulations containing 25% croscarmellose sodium compared to the pure drug and without super disintegrant glimepiride tablet. FTIR studies did not indicate any excipient incompatibility, either during mixing or after compression. Optimized formulation exhibited good results in the decrease in blood glucose in rats when compared to the pure drug and marketed product.Conclusion: Form the results if this study it can be concluded that prepared optimized fast disintegrating tablets of glimepiride are the better option to treat diabetes.Keywords: Superdisintegrants, Fast disintegrating tablets, Disintegration time, Water absorption ratio, Wetting time, Dissolution, Dynamic studie

NOVEL SUBCUTANEOUS SUSTAINED RELEASE NANOPARTICLES ENCAPSULATING LOW MOLECULAR WEIGHT HEPARIN (LMWH): PREPARATION, CHARACTERIZATION AND EVALUATION

Objective: The objective of the current research work was to prepare and evaluate novel subcutaneous sustained release polymeric nanoparticles for low molecular weight heparin (LMWH).Methods: In this study, we prepared subcutaneously administered polymeric nanoparticles encapsulating LMWH using different grades of polycaprolactons (PCL) (14k, 45k, 80k) and 0.1% Polyvinyl alcohol (PVA) solution as surfactant by employing water–in-oil in-water (w/o/w) emulsion and evaporation method. The formulated nanoparticles were evaluated for size, shape, zeta potential, in vitro drug release, and in vivo biological activity (anti factor Xa activity) using standard kit, antithrombotic activity in thrombosis induced rat model. Drug and polymer interactions in the nanoparticles were evaluated using Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD).Results: Scanning electron microscopic (SEM) studies on the nanoparticles confirmed the formation of spherical particles with smooth surface. The size of the formed nanoparticles were about 415-495 nm. The % entrapment of nanoparticles was found to be between 69-81%. Nanoparticles showed slow and sustained pattern of release for about 59-65 % in 48 h. Optimized nanoparticles exhibited excellent improvement in pharmacokinetic parameters and showed good antithrombotic activity, Activated partial thromboplastin time (aPTT) activity when compared to free drug. FTIR studies indicated that there was no loss in chemical integrity of the drug upon fabrication into nanoparticles. XRD results demonstrated that the drug changed its physical form in the formulation.Conclusion: The results of this study revealed that subcutaneous nanoparticles were excellent candidates for sustained drug delivery of LMWH to avoid repeated subcutaneous administration.Keywords: Low molecular weight heparin, Subcutaneous, Stability, Polycaprolactone, Venous thrombosis, Activated partial thromboplastin timeÂ

Development of novel risperidone implants using blends of polycaprolactones and in vitro in vivo correlation studies

The objective of this study was to develop a novel implant containing risperidone intended for long-term treatment in Schizophrenia utilizing in vitro in vivo correlation (IVIVC) studies. Different implants (F1-F8) containing an antipsychotic drug, risperidone, were prepared using a hot melt extrusion technique by taking polycaprolactones of different molecular weights (Mwt. 15000, 45000, 80000) either alone or as their blends, and PLGA (75:25). The implants contained 40% of the drug. After fabrication, the implants were characterized for various in vitro properties such as drug release and physical strength. Prior to conducting drug release studies, optimum drug release method was developed based on IVIVC studies. An optimized formulation based on drug release and physical strength at the end of fabrication was selected from the various implants fabricated. The bioactivity, reversibility, and IVIVC of optimized formulation were determined using pharmacokinetic studies in rats. Short-term stability studies were conducted with optimized formulation. Drug release depended on polymer molecular weight. Implant fabricated using 50:50 polycaprolactone 45,000 and polycaprolactone 80,000 was considered optimized implant. Optimized formulation selected released the drug for 3-months in vitro and was physically rigid. The optimized implant was able to release the drug in vivo for a period of 3 months, the implants are reversible throughout the delivery interval and, a 100% IVIVC was achieved with optimized implant, suggesting the development of 3-month drug-releasing implant for risperidone. The optimized implant was stable for 6 months at room temperature (25°C) and 45°C. A novel implant for risperidone was successfully prepared and evaluated