Hot-melts in buccoadhesive patches: An approach for bioavailability enhancement of highly-metabolized drugs with short elimination half-life

• TIZ hot-melts in buccoadhesive patches were successfully prepared.
• The hot-melt patch controlled TIZ release in vivo with a median Tmax of 6 h.
• It enhanced bioavailability of TIZ 2.57 folds compared to immediate-release tablet.
• Dose reduction and minimizing frequency of administration could be achieved.
• Suitable for delivering highly metabolized drugs with short elimination half-lives.

The present study deals with the inclusion or incorporation of hot-melts into buccoadhesive patches. Our aim is to develop a patient-friendly dosage form that is capable of extending release of short elimination half-life drugs so to decrease dosing frequency and to increase the bioavailability of highly-metabolized drugs with the ultimate aim of dose reduction. Tizanidine hydrochloride (TIZ) was used as a model drug. TIZ was incorporated into Compritol-based hot-melts, and then further formulated into buccal patches prepared using HPMC, PVA and Polyox. A Central Composite Face-centered Design was employed to statistically optimize the formulation variables; HPMC solution/PVA solution weight ratio, Compritol/TIZ ratio in the hot-melts and percentage Polyox. The optimized formula suggested by the software was successful in controlling drug release, where 85% of TIZ was released after 4 h and the patch showed acceptable mucoadhesion properties. Pharmacokinetic parameters of TIZ from the optimized formula were compared to those of the immediate release tablet, Sirdalud®, as reference in human volunteers using a randomized crossover design. Significant increase was observed for Cmax, Tmax, AUC(0–12) and AUC(0–∞). The increase in relative bioavailability of TIZ from the optimized formula was 2.57 folds.

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