Exploration of polymethacrylate and Hypromellose for the development of a non-sulfhydryl ACE inhibitor mucoadhesive system using Box-Behnken design: in-vitro and ex-vivo evaluation.

PURPOSE: To counteract early morning pathology like hypertension a time-dependent release of the drug is required. This study is focused to formulate a pulsatile and mucoadhesive drug delivery system of an ACE inhibitor Perindopril Erbumine. METHOD: Two matrix tablets were punched with Eudragit RSPO, Eudragit RLPO, and HPMC K15M using a 3-3-3 Box-Behnken Design of Response Surface Methodology. Based on the design-optimized formulation P1T3 and P2T8 were coated for a lag time with compression coating of HPMC K4M and a blend of 1:1 ratio of ethylcellulose and carbopol polymer and further encapsulated in a Eudracap™ capsule to provide gastric resistance. RESULT: The in-vitro release data confirmed an initial pause phase of 4.5 h then release of the drug for 5.2 ± 0.3 h to cope with the early morning rush in blood pressure. After that, a gap of 6 h and then sustained release of the drug for 10.5 ± 0.5 h. From the ex-vivo study, mucoadhesive strength was obtained as 55.13 ± 0.03 gm and 56.39 ± 0.02 gm for P1T3 and P2T8 respectively. The lag time for coated tablet P1T3 came to 2.15 ± 0.15 h and for P2T8 11.9 ± 0.10 h proving the coating efficiency of polymers. CONCLUSION: The current study strongly suggests that perindopril Erbumine in association with Eudragit and Hypromellose polymer can open a path for the time-regulated release of the drug for hypertension chronotherapy with less risk of dose dumping.

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

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.