QUALITY-BY-DESIGN ASSISTED DEVELOPMENT AND EVALUATION OF A MICROBALLOON-BASED GASTRORETENTIVE DRUG DELIVERY SYSTEM

Objective: To develop and optimize levofloxacin-loaded floating microballoons for gastroretentive delivery to improve local antibiotic concentrations against Helicobacter pylori (H. pylori), prolong gastric residence, and achieve extended release using a Quality by Design (QbD) approach. Methods: Microballoons were prepared by a modified emulsion solvent diffusion technique using levofloxacin hemihydrate, eudragit RS100 (Eu RS100) and ethyl cellulose (EC) in ethanol: dichloromethane (1:1 v/v) and stabilized with 0.75% PVA. A Plackett–Burman design screened formulation and process variables; significant factors were optimized by a central composite design (CCD). Characterization included entrapment efficiency (EE), percentage yield, particle size and zeta potential, in vitro buoyancy, dissolution testing, fourier transform infrared spectroscopy, powder x-ray diffraction, differential scanning calorimetry, scanning electron microscopy and ICH Q1A (R2) stability testing at 25°C/60% RH and 40°C/75% RH. Data were modelled in Design-Expert® and kinetics evaluated. Results: Plackett–Burman screening identified EC, Eu RS100 and stirring speed as critical. CCD optimization selected EC 400 mg and Eu RS100 392 mg (desirability 0.789) at fixed stirring (300 rpm). The validated optimized formulation showed a percentage yield of ≈85%, EE of 74.7% ± 1.2%, a mean particle size of 266.3 ± 4.2 µm, a zeta potential between −15 and −25 mV, and a buoyancy of 79.1% ± 2.4% at 12 h. Twelve-hour cumulative release was 64.7 % ± 1.9 % with sustained, controlled release. Fourier transform infrared spectroscopy spectroscopy showed small changes in the spectrum that were consistent with hydrogen-bonding interactions (the drug did not break down). Powder x-ray diffraction and differential scanning calorimetry showed that levofloxacin lost its crystalline structure (from partial to complete amorphization) in the polymer matrix. Scanning electron microscopy verified the presence of spherical, hollow, porous microballoons characterised by distinct internal cavities. In terms of appearance, drug content, buoyancy, or release profile, stability testing revealed no significant changes. Conclusion: Levofloxacin-loaded floating microballoons, developed using a QbD framework, provided high entrapment, prolonged gastric buoyancy and controlled release with robust stability. The formulation is a promising gastroretentive platform to enhance local gastric drug concentration and potentially improve H. pylori eradication.