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