Characterization of bilayered matrix-type mucoadhesive buccal films containing tizanidine hydrochloride and piroxicam

M Yasmin Begum,Ali Alqahtani

doi:10.4314/tjpr.v20i11.1

Abstract

Purpose: To formulate and characterize tizanidine hydrochloride (TZN) and piroxicam (PRX)-loaded bilayer mucoadhesive buccal films with an intention to improve the bioavailability and patient compliance in pain management.Methods: Bilayer buccal films were prepared by solvent evaporation technique using hydroxypropyl methylcellulose (HPMC) 15cps and polyvinylpyrrolidone (PVP K30 as immediate release (IR) layer forming polymers and HPMC K15 M, PVP K 90 along with various muco adhesive polymers (Carbopol P934, sodium alginate, etc), as sustained release (SR) layer forming polymers. The prepared films werecharacterized for thickness, weight variation, folding endurance, surface pH, swelling index,mucoadhesive strength, in vitro residence time, in vitro drug release, ex vivo permeation and drug release kinetics.Results: The prepared films were of largely uniform thickness, weight and drug content. Moisture loss (%) and folding endurance were satisfactory. Surface pH was compatible with salivary fluid. Disintegration time was 85 s for F1 and 115 s for F2 of IR films. In vitro dissolution studies showed 99.12 ± 1.2 % (F1) and 90.36 ± 1.8 % (F2) were released in 45 min. Based on the above results, F1 was chosen as the optimum formulation to be combined with SR layer of TZN. Amongst the SR layers of TZN in vitro drug release. The findings show that of F2 was 98.38 ± 0.82 % and correlated with ex vivo release. Drug release followed zero order release kinetics and mechanism of drug release was non-Fickian type diffusion. In vitro residence time was greater than 5 h.Conclusion: The findings show that the bilayer buccal films demonstrate the dual impact of deliveringPRX instantly from the IR layer, with good controlled release and permeation of TZN from the SR layer, thus providing enhanced therapeutic efficacy, drug bioavailability and patient compliance.

Highlights

Systemic target of drugs via oral cavity’s buccal mucosal membrane is termed as buccal drug delivery system
A retrospective study conducted by Smith et al in 2001 states that tizanidine hydrochloride (TZN) at low dose in combination with a regular longacting NSAID might be useful in treating analgesic rebound headache
The film was completely dissolved by constant stirring and drug content was measured in phosphate buffer solution pH 6.8 by UV-spectrophotometer at 320 nm for TZN and 354 nm for PRX [4, 8, 10] against blank

Summary

INTRODUCTION

Systemic target of drugs via oral cavity’s buccal mucosal membrane is termed as buccal drug delivery system. A retrospective study conducted by Smith et al in 2001 states that tizanidine hydrochloride (TZN) at low dose in combination with a regular longacting NSAID might be useful in treating analgesic rebound headache. Bilayered mucoadhesive buccal film containing piroxicam (PRX) loaded immediate release (IR) layer and TZN loaded sustained release (SR) layer was prepared to have better patient compliance and enhanced bioavailability. To improve the bioavailability of TZN by circumventing the large hepatic first-pass elimination, the drug was chosen as a suitable one for incorporating into muco adhesive buccal film. The drug/polymer mixture was poured into petri plate, dried at room temperature, stored in desiccator after drying [7]. Tizanidine hydrochloride (mg PVP K90 (%w/w) Sodium alginate (%w/w) HPMC K15M (%w/w) Carbopol P 934 (%w/w) HPMC K4 M (%w/w) Chitosan (%w/w) Propylene glycol (%v/v) Water (mL)

F2 F3 F4

RESULTS

Evaluation of bilayer buccal film

DISCUSSION

CONCLUSION

Conflict of Interest