DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF METFORMIN AND EMPAGLIFLOZIN
Keywords:
Rifaximin, Enteric-coated pellets, Small intestinal delivery, EUDRAGIT® L30D-55, Extrusion-spheronization, In vitro drug release.Abstract
Rifaximin is a poorly absorbed rifamycin antibiotic widely used in the treatment of gastrointestinal disorders such as Traveler's Diarrhea, Irritable Bowel Syndrome with Diarrhea (IBS-D), Hepatic Encephalopathy, and Small Intestinal Bacterial Overgrowth (SIBO). Due to its localized action within the gastrointestinal tract, targeted delivery of rifaximin to the small intestine can improve therapeutic efficacy and reduce premature drug release in the stomach. The present study aimed to formulate, develop, and evaluate enteric-coated rifaximin pellets for targeted small intestinal delivery using a multiparticulate drug delivery approach.
Preformulation studies including organoleptic evaluation, solubility study, melting point determination, Fourier Transform Infrared Spectroscopy (FTIR), and calibration curve preparation were carried out to assess the physicochemical characteristics and compatibility of rifaximin with selected excipients. Drug-loaded pellets were prepared by layering rifaximin onto sugar spheres using Hydroxypropyl Methylcellulose (HPMC E5) as a binder in a fluidized bed processor. A barrier coating was subsequently applied using HPMC E5 to prevent interaction between the drug layer and enteric coating polymer.
Enteric coating was performed using Eudragit® L30D-55 as the enteric polymer, Diethyl Phthalate as a plasticizer, Tween 80 as a surfactant, and Talc as an anti-tacking agent. Formulation optimization was carried out through the preparation of multiple trial batches, and the optimized formulation was selected based on assay, acid resistance, and dissolution performance. Quality by Design (QbD) principles were applied to identify Critical Quality Attributes (CQAs), Critical Material Attributes (CMAs), and Critical Process Parameters (CPPs) affecting product quality.
The prepared pellets were evaluated for percentage yield, particle size distribution, bulk density, tapped density, Carr's Index, Hausner Ratio, angle of repose, friability, moisture content, drug content, assay, enteric resistance, and in-vitro dissolution behavior. The optimized formulation exhibited satisfactory physicochemical properties, excellent flow characteristics, low friability, high drug content uniformity, and acceptable assay values. The enteric-coated pellets demonstrated excellent resistance in acidic medium with minimal drug release during the acid stage and more than 80% drug release in phosphate buffer pH 6.8, confirming successful intestinal targeting.
The results of the study indicated that Eudragit® L30D-55-based enteric-coated rifaximin pellets can effectively protect the drug from gastric conditions and provide targeted drug release in the small intestine. Therefore, the developed multiparticulate pellet system represents a promising approach for improving the therapeutic performance of rifaximin intended for intestinal delivery.
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