Trimetazidine Dihydrochloride Pulsatile–Release Tablets for the Treatment of Morning Anginal Symptoms: Dual Optimization, Characterization and Pharmacokinetic Evaluation

Title:Trimetazidine Dihydrochloride Pulsatile–Release Tablets for the Treatment of Morning Anginal Symptoms: Dual Optimization, Characterization and Pharmacokinetic Evaluation

Volume: 18 Issue: 8

Author(s): Abdelrahman I. Othman*, Maha M. Amin, Sherif K. Abu-Elyazid and Ghada A. Abdelbary

Affiliation:

• Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo,Egypt

Keywords: Trimetazidine dihydrochloride, chronic stable angina, dual optimization, box-behnken, pulsatile release, in-vivo pharmacokinetic study.

Abstract:

Aim: This research work aimed to target the early morning peak symptoms of chronic stable angina through formulating antianginal drug, Trimetazidine (TMZ) in a pulsatile-release tablet.

Methods: The core formulae were optimized using 22.31 factorial design to minimize disintegration time (DT) and maximize drug release after 5 minutes (Q5min). Different ratios of Eudragit S100 and Eudragit L100 were used as a coating mixture for the selected core with or without a second coating layer of hydroxypropyl methylcellulose (HPMC E50). The different formulation variables were statistically optimized for their effect on lag time and drug release after 7 hours (Q7h) using Box- Behnken design. The optimized formula (PO) was subjected to stability study and pharmacokinetic assessment on New Zealand rabbits.

Results: The optimal core (F8) was found to have 1.76 min disintegration time and 61.45% Q5min PO showed a lag time of 6.17 h with 94.80% Q7h and retained good stability over three months. The pharmacokinetics study confirmed the pulsatile–release pattern with Cmax of 206.19 ng/ml at 5.33 h (Tmax) and 95.85% relative bioavailability compared to TMZ solution.

Conclusion: Overall pulsatile-release tablets of TMZ successfully released the drug after a desirable lag time, providing a promising approach for early morning anginal symptoms relief.

Cite this article as:

Othman I. Abdelrahman *, Amin M. Maha , Abu-Elyazid K. Sherif and Abdelbary A. Ghada , Trimetazidine Dihydrochloride Pulsatile–Release Tablets for the Treatment of Morning Anginal Symptoms: Dual Optimization, Characterization and Pharmacokinetic Evaluation, Current Drug Delivery 2021; 18 (8) . https://dx.doi.org/10.2174/1567201818666210212095932