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

(E-pub Ahead of Print)

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

Journal Name: Current Drug Delivery

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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.

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

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1567201818666210212095932
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