Development of a Chronomodulated Pulsatile Drug Delivery System for Time-Controlled Delivery of Ranirestat in Diabetes Mellitus

Background: A chronomodulated, film-coated oral tablet of Ranirestat was intended for the management of diabetesassociated complications. Objective: This study outlines the development and evaluation of the chronomodulated, film coated orally administered Ranirestat tablet. Methods: The Preformulation studies were carried out to characterize the drug and to ensure its compatibility with the selected excipients, which included solubility screening, melting point determination, FTIR spectroscopy, and UV–Visible spectrophotometry. The optimization of excipients' ratio was performed by direct compression to produce the core tablet with the acceptable tablet properties. The selected tablets of six core batches (F1–F6) were evaluated for weight variation, hardness, thickness, friability, disintegration time and drug content uniformity with F6 tablets showing the best results and advancing for film coating. Results: The coated F6 tablets had good mechanical strength, uniform drug content and a time dependent release profile; releasing more than 90% of the loaded drug release In-Vitro in 60 minutes. In addition, the swelling study showed that the coating system was pH responsive as hydration increased as the pH increased, with the highest amount of hydration at pH 7.4. F6 showed excellent dissolution properties with a good correlation. Conclusion: The polymeric film prohibited, but did not stop, premature drug release, therefore it is considered a delayed/modified-release formulation and not a totally completed pulsatile system with a clearly defined lag phase that would require further optimization of the polymeric film. Polymeric film did not prevent, but delayed, the drug release, thus the system could be considered a delayed/modified-release system, and further optimization of the polymeric film would be required to have a clear lag period suitable for chronotherapeutic dosing.