Exploration of Parteck® SRP 80 and Hypromellose for Chronomodulated Release of LTD4 Receptor Antagonist and Statistical Optimization Using Central Composite Design.

Abstract

To manage early morning symptoms of nocturnal bronchial asthma, a chronotherapeutic drug delivery system (ChrDDS) of montelukast sodium was designed and developed utilizing non-saccharide, fully synthetic Parteck® SRP 80, and hydrophilic cellulose derivative hydroxypropyl methylcellulose (HPMC). Recurrent lag phase, each followed by the release of a fraction of the drug dose, can be achieved by formulating a "tablets in a capsule" system containing more than one compressed coated tablet encapsulated in an enteric-coated capsule. Lag time in this study was controlled by the compressed coating of HPMC K4M and a blend of ethyl cellulose and Carbopol polymer. Assembly of the system includes two compressed coated tablets encapsulated in a capsule which was further proceeded for enteric coating in a conventional, a novel wax-based, and a Eudracap™ enteric-coated capsule. The optimized formulation of directly compressed tablets of Parteck ® SRP 80 showed a hardness of 8.8 kg/cm2 which is 1.25-fold higher than wet granulated tablets of HPMC. In vitro release data of matrix tablets of Parteck® SRP 80 demonstrated controlled release of drug for a duration of up to 10.8-11 h with changing ratio of polymer and filler. Eudracap™ capsule showed a minimum acid uptake value of 1.75%. The current approach can open a path for the time-regulated release of montelukast that may be beneficial for individuals with episodes of asthma attacks mostly in the early morning.