Formulation of Tablets in Capsule system: Statistical optimization for chronotherapeutic drug delivery of propranolol hydrochloride

Abstract

Chronic diseases like asthma, hypertension and rheumatoid arthritis requires prompt release of drug as per the disease condition. Conversely, extended release systems can only maintains the drug concentration with in therapeutic range for prolonged period of time, which not be the primary requisite for the foresaid diseases. The early morning surge of blood pressure was reported to be associated with a high risk of hemorrhagic stroke and cardiac death. This can be overcomeby programmed lag time, through designing of chronotherapeutic drug delivery systems (CDDS), that can be beneficial for the delivery of Propranolol hydrochloride at required time. The goal of the present study is to explore and optimize various parameters in designing Tablets in Capsule system (TCS) using response surface methodology to release the medication as per the chronological conditions of the disease. Initially, coating of capsule body was optimized in order to maintain its integrity for more than 12 h. Subsequently, erodible tablet formulation was optimized via a face-centered central composite design. Concentration of guar gum (X1) and total erodible tablet weight (X2) were selected as independent variables and these were studied at five different levels (±1 - factorial points, ± 1.141- axial points and center point −0) to optimize the cumulative drug release at the end of 5 h [CDR (6 h)- Y1] and time taken to release 98% of drug [T 98% - Y2], using Design Expert 11. On basis of Global desirability function (D) criteria, formulation with guar gum concentration of 35.589 mg and total tablet weight of 150 mg can accomplish the prerequisites of optimum formulation and the use of such combination shows, 6.946% of CDR at the end of 5 h and time taken to release 98% of Propranolol hydrochloride was found to be 12 h. Chronotherapeutic system requires of at least 5–6 h of lag time and followed by the complete drug release within 12 h, that matches with the optimized formulation. However, this work should extend to in vivo pharmacokinetic studies to conform the in vitro in vivo correlation.