Development and Evaluation of Fast Dissolving Sublingual of Cilnidipine Nanocrystals for Enhanced Solubility, Dissolution and Bioavailability

The present work involves the formulation of sublingual films of Cilnidipine, a BCS Class II drug, faces a major problem due to its bioavailability of 13% in oral dosage form. To increase solubility and bioavailability, nanocrystals were prepared using antisolvent crystallization technique. Solubility of prepared Cilnidipine crystals were studied then subjected for FTIR, DSC, SEM, XRD and In-vitro dissolution studies for characterization and evaluation. This reveals a significant increase in drug dissolution and solubility with a decrease in particle size compared to pure Cilnidipine. The crystals also showed compatibility with the drug and excipients, with smaller crystals. Powder X-ray diffraction revealed decreased intensity of peaks compared to pure drug. Crystals prepared using ethanol as a solvent under ultrasonication (Probe) showed the highest solubility and dissolution rate at 60 minutes, with better results in drug content and compared to pure drug. Anti-solvent crystallization method was successful in formulating cilnidipine crystals with high dissolution rates to eliminate solubility-related bioavailability issues. Further Cilnidipine crystals were formulated into Fast Dissolving Sublingual Films by solvent-casting method. The fast-dissolving films of Cilnidipine were prepared using HPMC E5, HPMC E15 and HPMC E50 as film forming polymers and PEG400 was used as plasticizer. Films were evaluated for physical characteristic such as uniformity of weight, thickness, folding endurance, drug content uniformity, surface pH, tensile strength. Fourier transform infrared spectroscopy and In- vitro release studies. All films were found to be satisfactory when evaluated for thickness, weight uniformity, folding endurance and drug content. The optimized formulation F2 showed satisfactory pH and drug content (93.7%). The in-vitro drug release in optimized formulation F2 was found to more than 95.55% within 10 min and satisfactory stability. Fast dissolving films of Cilnidipine crystals can be considered suitable for clinical use in the treatment of Hypertension and hypertensive associated vascular disorders where a quicker onset of action is desirable along with the convenience of administration.