Investigation of Groundnut Shell Powder as Potential Super Disintegrant in Chronotherapeutic Delivery of Sacubitril–valsartan

Abstract

ABSTRACT Context: Chronotherapeutic delivery of antihypertensives plays a potential role in the treatment by providing a therapeutic amount of drug at the target site in the body. Sacubitril–valsartan (SV), an angiotensin receptor neprilysin inhibitor, has been indicated for the treatment of hypertension. The study explores the formulation and evaluation of compression-coated tablets (CCTs) of SV using a natural super disintegrant in the core tablet for chronotherapeutic drug delivery. Aim and Objective: The main objective of the current investigation is to study the applicability of groundnut shell powder (GSP) as super disintegrant and its role in chronotherapeutic drug delivery. Materials and Methods: Core tablets of SV were prepared using different concentrations of natural excipient (GSP) and compression coated. The CCT was evaluated for the postcompression tableting properties, in vitro drug release, Fourier transform infra red spectroscopy (FTIR), and stability studies and compared the disintegrating property with a synthetic excipient (crospovidone). Results: The results of the in vitro dissolution performance of core tablets indicated that the incorporation of GSP as a super disintegrant significantly reduced the disintegration time. Optimized core tablets were subjected to compression coating using a graded concentration of cellulose acetate phthalate as coating polymer and evaluated tableting properties and dissolution performance. Among all the formulations, CCT5 with 8% GSP in the core, coated with 300 mg coating polymer shown 6 h lag time followed by the rapid release of the drug within 1 h. Accelerated stability studies on optimized formulation revealed that there were no significant changes in the tableting parameters after storage indicating the stability of the formulation. Conclusion: The use of natural disintegrant in the core tablet offers a promising approach for rapid release of drug from CCT after a lag time of 6 h to achieve chronotherapy of SV.