Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutics

Risedronate sodium (RS) is a potent inhibitor of bone resorption; having an extreme poor permeability and limited oral bioavailability (0.62%). RS should be orally administered under fasting conditions, while keeping in an upright posture for at least 30 min, to diminish common gastroesophageal injuries. To surmount such limitations, novel Risedronate-chitosan (RS-CS) crosslinker-free nebulizable microspheres were developed adopting quality by design (QbD) approach and Risk assessment (RA) thinking. RS:CS ratio, surfactant (Pluronic® F127) concentration, homogenization duration, speed and temperature were identified using Ishikawa diagrams as the highest formulation- and process-risk factors affecting the critical quality attributes (CQAs); average particle size (PS) and entrapment efficiency (EE%). The risk factors were screened using Plackett-Burman design and the levels of the most significant factors were optimized using a multi-level factorial-design to explore the optimized system with the least PS, maximum EE% and a prolonged drug release profile. The optimized system (B6) was developed at RS:CS ratio of 1:7, a surfactant concentration of 2% (w/v) and a homogenization speed of 14000 rpm. It revealed well correlation with QbD theoretical prediction where, positively charged (47.9±3.39 mV) discrete, spherical microspheres (3.47±0.16 æm), having a high EE% (94.58±0.19%) and prolonged RS release over 12 hours (Q12h, 89.70±0.64%) were achieved

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