Repaglinide

The present study focuses on the development and evaluation of sustained release matrix tablets of Repaglinide, a short-acting antidiabetic drug, using processed Aloe vera mucilage as a natural release-modifying agent. The primary objective was to extend the drug release profile, reduce dosing frequency, and improve patient compliance. Aloe vera mucilage was extracted, processed, and characterized for its physicochemical properties, including swelling index, viscosity, and compatibility with the drug through FTIR and DSC studies. Matrix tablets were formulated using the wet granulation method with varying concentrations of Aloe vera mucilage and evaluated for pre-compression and post-compression parameters such as hardness, friability, weight variation, drug content, and in vitro drug release. The release data were analyzed using various kinetic models to determine the mechanism of drug release. Among the formulations, the batch containing a higher concentration of Aloe vera mucilage demonstrated a sustained release of Repaglinide over 12 hours, following a non-Fickian diffusion mechanism. Comparative analysis with synthetic polymers revealed that Aloe vera mucilage exhibited comparable or superior release-controlling potential, supporting its use as an effective natural excipient. The study concludes that processed Aloe vera mucilage can be successfully employed as a cost-effective, biocompatible, and efficient release modifier in the formulation of sustained release matrix tablets of Repaglinide.

The present work describes Stability indicating RP-HPLC and Simultaneous equation UV spectrophotometric method for the quantitative determination of Repaglinide and Sitagliptin phosphate. The parameters Specificity, linearity, accuracy, precision, detection limit, quantitation limit, Robustness and system suitability tests were studied and their results were complied to ICH guideline Q2 (R1).  Chromatography was carried out by reverse phase technique on an RP-18 with mobile phase composed of Acetonitrile: Phosphate buffer (65:35; % v/v) adjusted to pH 3.5 with 10% orthophosphoric acid) with flow rate 1 ml/min. Both drugs were eluted, isocratically using detection wavelength 228 nm. Simultaneous equation UV spectrophotometric method was performed and two wavelengths 240 nm (λmax of Repaglinide) and 267 nm (λmax of Sitagliptin phosphate) were selected for the formation of simultaneous equation. The A (1%, 1cm) was determined at both the wavelengths selected for each drug. A set of two simultaneous equations were formed as Cx and Cy. Methanol used as Solvent (diluent) for UV method. For proposed methods, the linearity for both methods were obtained in the concentration range of 0.5-2.5 μg/ml for Repaglinide and 50-250 μg/ml for Sitagliptin phosphate. Statistical analysis by student’s t-test showed no significance difference between the results obtained by these two methods. The suitability of method for the quantitative determination of Repaglinide and Sitagliptin phosphate was proved by validation. The proposed methods and its results had been successfully applied and validated statistically to the simultaneous estimation of Repaglinide and Sitagliptin phosphate in their combination for quality analysis.

The aim of the present investigation was to design a mucoadhesive liposomal system of Repaglinide for the treatment of type - 2 diabetes mellitus that is capable of delivering entrapped drug over an extended period of time. Mucoadhesive liposomal formulations were prepared by using different ratio of lecithin and cholesterol by thin film hydration technique followed by coating of liposomes by 0.1 % w/v and 0.3 % w/v of chitosan and were evaluated for entrapment efficiency, particle size, zeta potential, surface morphology and in-vitro drug release. Particle size and zeta potential of the F2 and C2F2 formulation was found to be 413.5 nm, 830.9 nm and -40.9 mV, -46.8 mV respectively. Coating of liposomes resulted increase in particle size and also increases the zeta potential.  Highest entrapment efficiency was observed in F1, CF1 and C2F2 90%, 95% and 94%. The percent drug release from F1-F3, CF1-CF3 and C2F1-C2F3 was observed as follows F1- 79.04%, F2- 76.77%, F3- 64.32%, CF1-66.65%, CF2- 62.12%, CF3- 56.54% and C2F1- 59.1%, C2F2-56.56%, C2F3- 53.45% which follows first order drug release and non-Fickian diffusion mechanism. And mucoadhesive strength from CF2- 60%, C2F2- 74%.

Buccal mucosa is a potential site for the delivery of drugs to the systemic circulation in a sustained manner; avoiding the first-pass metabolism. The goal of present investigation was to design and evaluate mucoadhesive buccal films of Repaglinide in order to avoid first-pass effect and release the drug for extended period of time. The Buccal films were formulated using polymers, Carbopol-971P and HPMC K4M, by solvent casting method; using PEG 400 as plasticizer. In this study, an attempt has been made to prepare Repaglinide inclusion complex; to enhance its solubility and was incorporated into the mucoadhesive buccal films in order to improve the bioavailability. A comparative study has been done between; uncomplexed Repaglinide loaded buccal films and inclusion complex loaded buccal films. The films prepared were evaluated for various physicochemical parameters and in vitro drug release. It was observed that inclusion complex loaded buccoadhesive films showed higher cumulative percentage of drug release at the end of 8 hours. The release data obtained was analyzed using various mathematical models. The Repaglinide loaded films followed zero order kinetics with principle mechanism of drug release being fickian diffusion. Whereas the inclusion complex loaded films followed zero order kinetics and exhibited non-fickian diffusion mechanism. HCC1 formulation having acceptable physicochemical parameters and with highest cumulative percentage of drug release (95.18%) at the end of 8 hours was chosen as optimum formulation and its short term stability studies revealed adequate stability of the formulation.

  In the present investigation an attempt was made to formulate fast dissolving tablets using BCS class II drug Repaglinide, ie low solubility and high permeability to form an inclusion complex to improve the dissolution rate, thus enhancing the bioavailability. Beta-CD inclusion complex was made in varying ratios 1:1, 1:3 and 1:5 of drug and polymer by solvent evaporation method. The complexes were evaluated for phase solubility, drug content and drug release. Phase solubility study revealed AL type indicating linear increase in solubility with increase in the carrier concentrations. The inclusion complex 1:1 ratio prepared by spray dried was studied for drug content uniformity which was ranging from 85-98%, FTIR showed no any compatibility of the drug and beta-CD; DSC and XRD showed distinct loss of drug crystallinity accounting for enhancement in the dissolution rate. SEM revealed spherical shape of the inclusion complex. The drug release study was carried out in 0.1N HCL using USP type paddle dissolution apparatus revealed to be 93% within 5 mins. The FDT was formulated by direct compression method six batches of tablets were prepared with varying ratios of superdisintegrants (F1-F6). The tablets were evaluated for hardness, friability, weight variation, disintegration which was found within the official range, drug content ranging from 89-94%. The formulation F3 containing Crosspovidone was optimized which showed maximum drug release of 98% within 10 mins. Kinetics of drug release from all the tablets followed zero order release with non-Fickian type diffusion. Key words: Repaglinide, Beta- Cyclodextrin, Spray drying and fast dissolving tablets