QUALITY-BY-DESIGN DEVELOPMENT OF CURCUMIN-LOADED NANOSUSPENSION FOR ENHANCED SOLUBILITY AND SOLIDIFICATION INTO ORAL THIN FILMS

Objective:This study aimed to develop and optimize a curcumin (CUR) nanosuspension (NS) to enhance solubility using a Quality-by-Design approach and to solidify the NS into oral thin films (OTFs) as a patient-friendly dosage form. Methods: NS was prepared using high shear homogenization (HSH). Stabilizer concentration and homogenization time were optimized using a factorial design, with particle size, polydispersity index (PDI), and drug loading defined as critical quality attributes. The optimized NS was characterized forsaturation solubility, in vitro dissolution, and in vivo pharmacokinetics and solidified into OTFs by solvent casting and evaluated. Results: The optimum stabilizer concentration of SLS (0.7%w/v) and homogenization time (190 mins) resulted in NS witha particle size (259.8±30 nm),PDI (0.402±0.034), drug loading (61±1.1%),15-fold increase in saturation solubility andfaster dissolution. Pharmacokinetic studyrevealed only modest improvement in oral bioavailability of NS (~1.2-fold) higher relative bioavailability as compared to pure drug. OTFs containing NS demonstrated good mechanical integrity, rapid disintegration(26 sec), preservation of nano-sized particles post-solidification (277.8±46 nm) and enhanced dissolution. Conclusion: A Quality-by-Design-based NS formulation of CUR markedly improved solubility and was successfully solidified into OTFs, offering a stable and convenient oral delivery system.