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

Abstract

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.

Graphical Abstract

Keywords:

• Eudragit RSPO
• Eudragit RLPO
• Box-Behnken design (BBD)
• Perindopril erbumine
• Ex-vivo

Acknowledgment

The management of PES University in Bengaluru, India is to be thanked by the authors for giving Mrs. Saniya Jawed a scholarship and all the facilities and assistance she needs to carry out this research. Thanks are given to Glenmark Pharmaceuticals Ltd. of Mumbai, India, for providing Perindopril Erbumine to the authors, and expressing thanks to Evonik healthcare, Essen, Germany for giving Eudragit polymers, and Eudracap™ ready-to-fill capsules.

Disclosure statement

The authors made a clear declaration of no conflicts of interest.

Additional information

Funding

No grants from funding organizations in the public, private, or nonprofit sectors have been given to this work.