Formulation development and in vitro in vivo evaluation of chronotherapeutic drug delivery system for the management of early morning pathologies

Abstract

The current research work comprises the design, development, and evaluation of a chronotherapeutic drug delivery system (ChrDDS) for early morning pathologies. The author has provided full detail of the work in this dissertation. The obtained results have been reviewed, explained, and compared to the studies reported earlier in the available literature in newlinethis domain. Early morning pathologies (EMP) are those disease conditions where symptoms vary as per the human circadian rhythm with the highest intensity of the symptoms in the early morning. Among all EMPs, asthma, and hypertension are the most widely spread and frequent pathological conditions. As per recent statistics from WHO, globally 235 million and 1.28 billion people are affected by asthma and hypertension respectively. To manage early morning symptoms of asthma and hypertension, a customized drug delivery system is required which delivers a higher dose of the drug in the early morning to cope with the severity of the symptoms, then sustained release for a longer time to maintain the therapeutic concentration. Both release phases must be separated by a lag or pause phase of drug release. A quottablets in a capsulequot system comprising more than one compressed coated tablet encapsulated in an enteric-coated capsule can be used to accomplish the recurrent lag phase, which is followed by the release of a fraction of the drug dose. Montelukast sodium (MTS) belongs to the leukotriene receptor antagonist category and is a BCS class II drug that inhibits bronchoconstriction and relaxes the smooth muscle resulting in easy breathing. From studies, it was found that MTS is the only leukotriene receptor antagonist which is highly efficient when dosed at the night. Till now there has been no chronotherapeutic formulated marketed with MTS. Henceforth, it has been selected to make once a day drug delivery system for asthma chronotherapy. Two matrix tablets of MTS were punched with hypromellose and Parteck® SRP80 and further coated with ethyl cellulose-carbopol blend