Background: Felodipine is a poorly water-soluble calcium-channel blocker with low systemic bioavailability after oral administration, attributed in the thesis to extensive first-pass metabolism and poor aqueous solubility. The present study investigated a combined crystal-engineering and buccal-film strategy to improve the aqueous solubility and ex vivo buccal permeation of felodipine.

Methods: Felodipine co-crystals were prepared by solvent-drop grinding with sorbitol, L-ascorbic acid, and oxalic acid at a 1:1 drug:coformer ratio. The highest-solubility co-crystal was further screened at 1:1, 1:1.5, and 1:2 ratios. The selected felodipine–sorbitol co-crystal was characterized by microscopy, SEM, FTIR, and PXRD. Co-crystal-loaded buccal films were prepared by solvent casting and optimized using a 3² factorial design with HPMC E15 and PVA as independent variables. Drug permeation at 8 h and mucoadhesive strength were the principal responses.

Results: The reported saturation solubility of felodipine was 1.97 mg/100 mL, compared with 3.2 mg/100 mL for the felodipine–sorbitol co-crystal. FTIR showed shifts in characteristic bands and PXRD showed a diffraction pattern distinct from the parent materials, supporting formation of a new solid form. Across the nine experimental film batches, the reported 8-h permeation response ranged from 65.52% to 96.82%, while mucoadhesive strength ranged from 4.3 to 8.4 g. The experimentally evaluated optimized formulation (F4) showed 94.59% ex vivo permeation at 8 h through goat buccal mucosa. Kinetic analysis gave R² values of 0.975, 0.861, 0.992, 0.684, and 0.981 for zero-order, first-order, Higuchi, Hixson–Crowell, and Korsmeyer–Peppas models, respectively, with n = 0.653.