Abstract

Oral clarithromycin therapy for Helicobacter pylori is limited by short gastric residence and variable intragastric exposure. Formulating clarithromycin in mucoadhesive gastroretentive granules (MGG) may extend the gastric residence time, increase the concentration, and control drug release at the site of action for a longer time, and improving bioavailability and therapeutic efficacy in eradicating H. pylori. Polymers with certain swelling ability and mucoadhesive properties are critical to produce MGG. Therefore, this study aims to explore various polymers for their potential as carriers for mucoadhesive gastroretentive dosage forms. Clarithromycin was mixed in a ratio of 1:1 with HPMC K15M, HPC MF, HEC 250 HHX, Carbomer (Carbopol 971p), or Polymethacrylates (Eudragit RS PO), and MGG were prepared using the wet granulation method. The yield of obtained dry granules was measured, then the size, moisture content, and flow properties were characterized. Muco-/bio-adhesive properties were analyzed based on adhesion strength and MGG retained during the ex-vivo study. The swelling index and drug release profile of MGG in HCl 0.1 N (pH 1.2) were analyzed. The results showed that all polymers produced free-flowing granules with effective hydration and gastric tissue adhesion. Among them, the Carbopol-based granules (F4) offered the best overall balance of rapid gel formation for early attachment, good ex-vivo retention to 8 hours, and prolonged release maintained to 12 hours. Release profiles were best described by the Higuchi kinetic model, consistent with diffusion and dissolution-controlled drug release mechanisms from a hydrated matrix with polymer swelling. This work provides the first direct, granule-form comparison of multiple polymers for mucoadhesive gastro-retentive delivery of clarithromycin. The Carbopol 971p matrix (F4) emerges as a promising carriers to prolong gastric residence and sustain local drug availability, supporting reduced dosing frequency and improved patient convenience. Future studies will optimize polymer ratios and evaluate in-vivo pharmacokinetics and antibacterial performance.

Key words: Clarithromycin, Mucoadhesives, Gastroretentive, Cellulose derivatives, Carbomer, Polymethacrylate