title: Hot-melts in buccoadhesive patches: an approach for bioavailability enhancement of highly-metabolized drugs with short elimination half-life.
abstract: 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(0-1). The increase in relative bioavailability of TIZ from the optimized formula was 2.57 folds.
authors.forename: Galal M
authors.initials: GM
authors.lastname: El Mahrouk
authors.forename: Omaima N
authors.initials: ON
authors.lastname: ElGazayerly
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Aboelwafa
authors.forename: Maie S
authors.initials: MS
authors.lastname: Taha
mesh_terms: D000278:Administration, Buccal; D000818:Animals; D001682:Biological Availability; D018592:Cross-Over Studies; D006207:Half-Life; D006358:Hot Temperature; D006801:Humans; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D013552:Swine; D013997:Time Factors; D057968:Transdermal Patch
chemical_list: D004364:Pharmaceutical Preparations