Abdelrahman I. Othman*, Maha M. Amin, Sherif K. Abu-Elyazid and Ghada A. Abdelbary Pages 1 - 15 ( 15 )
Objective: 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 methyl cellulose (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 pharmacokinetic study confirmed the pulsatile–release pattern with Cmax of 206.19 ng/ml at 5.33 h (Tmax), as well as 95.85% relative bioavailability compared to TMZ solution.
Conclusion: Overall pulsatile-release tablets of TMZ succeeded in releasing the drug rapidly after a desirable lag time, providing a promising approach for early morning anginal symptoms relief.
Trimetazidine dihydrochloride, chronic stable angina, dual optimization, Box-Behnken, pulsatile release, in-vivo pharmacokinetic study.
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Po. Box 11829, Cairo, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Po. Box 11829, Cairo, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Nasr City, Po. Box 11651, Cairo, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Po. Box 11562, Cairo