Formulation and Optimization of Misoprostol-Encapsulated Floating Microbeads for Gastric Ulcer Healing

Misoprostol, a synthetic prostaglandin E₁ analogue, is effective for gastric ulcer healing but suffers from a short half‑life (20–30 min), frequent dosing (3–4 times daily), and dose‑dependent gastrointestinal side effects due to systemic absorption. Gastroretentive floating microbeads offer a strategy to prolong gastric residence and deliver misoprostol locally. Floating microbeads were prepared by extruding a sodium alginate‑misoprostol‑NaHCO₃ dispersion into CaCl₂ solution. A Box‑Behnken design (BBD) was employed to optimize three independent factors: alginate concentration (1.5–2.5% w/v), NaHCO₃ concentration (0.5–1.5% w/v), and CaCl₂ concentration (6–9% w/v). Responses included encapsulation efficiency (%EE), floating lag time (FLT), and cumulative drug release at 12 h. The optimized formulation was characterized for particle size, morphology (SEM), swelling, mucoadhesion, in vitro release kinetics, and stability. In vivo pharmacodynamic study was conducted in an indomethacin‑induced gastric ulcer rat model (n=6/group) comparing optimized microbeads (once daily, 100 µg/kg) with plain misoprostol suspension (twice daily) and marketed Cytotec®. The optimized formulation (2.2% alginate, 1.2% NaHCO₃, 7.2% CaCl₂, alginate:chitosan 2:1) achieved %EE of 89.4 ± 1.6%, FLT of 42 ± 4 s, and 12‑h release of 88.6 ± 2.4%. SEM revealed spherical, porous beads. Release followed Korsmeyer‑Peppas kinetics (n=0.62, anomalous transport). The microbeads exhibited good swelling (183% at 2 h) and mucoadhesion (detachment time 8.2 h). In vivo, optimized beads reduced ulcer index by 83% (vs. 55% for plain drug, p<0.001), restored near‑normal histology, and significantly improved biochemical markers (MDA, GSH, SOD, MPO) compared to plain misoprostol. The formulation was stable for 12 months at 25°C/60% RH. Misoprostol‑loaded floating microbeads prepared by ionotropic gelation with effervescent agent provide sustained gastric retention, enhanced ulcer healing, and once‑daily dosing potential, overcoming the limitations of conventional misoprostol therapy.

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