Development of Mucoadhesive Buccal Film for Rizatriptan: In Vitro and In Vivo Evaluation

Abstract

The reduced therapeutic efficacy of rizatriptan in migraine treatment is primarily due to low oral bioavailability and extensive first pass metabolism. The purpose of this investigation was to optimize the thin mucoadhesive buccal film of rizatriptan and assess the practicability of its development as a potential substitute for conventional migraine treatment. Buccal films (FR1–FR10) were fabricated by a conventional solvent casting method utilizing a combination of polymers (Proloc, hydroxypropyl methylcellulose and Eudragit RS 100). Drug-loaded buccal films (F1–F4) were examined for mechanical, mucoadhesive, swelling and release characteristics. In vivo pharmacokinetics parameters of selected buccal film (F1) in rabbits were compared to oral administration. Films F1–F4 displayed optimal physicomechanical properties including mucoadhesive strength, which can prolong the buccal residence time. A biphasic, complete and higher drug release was seen in films F1 and F4, which followed Weibull model kinetics. The optimized film, F1, exhibited significantly higher (p < 0.005) rizatriptan buccal flux (71.94 ± 8.26 µg/cm2/h) with a short lag time. Film features suggested the drug particles were in an amorphous form, compatible with the polymers used and had an appropriate surface morphology suitable for buccal application. Pharmacokinetic data indicated a significantly higher rizatriptan plasma level (p < 0.005) and Cmax (p < 0.0001) upon buccal film application as compared to oral solution. The observed AUC0–12h (994.86 ± 95.79 ng.h/mL) in buccal treatment was two-fold higher (p < 0.0001) than the control, and the relative bioavailability judged was 245%. This investigation demonstrates the prospective of buccal films as a viable and alternative approach for effective rizatriptan delivery.

An Updated Overview of the Emerging Role of Patch and Film-Based Buccal Delivery Systems

“…The variation of pH and salivary constituents along with the flow rate of the saliva can influence the buccal absorption and subsequent clinical effect. Various in vitro studies can be carried out in simulated salivary fluid typically composed of potassium phosphate (1.6 g), sodium chloride (2.4 g) and calcium chloride (0.16 g) in a liter and the pH adjusted to 6.8 using sodium hydroxide [ 25 ].…”

“…In a recent investigation, we have successfully used bioadhesive, erodible polymer, Proloc 15 TM in combination with HPMC F4M and water insoluble polymer, eudragit RS 100 to develop buccal film for the efficient delivery of rizatriptan [ 25 ]. The optimized buccal film demonstrated significantly higher ( p < 0.005) rizatriptan buccal flux (71.94 ± 8.26 ng/cm 2 /h) and AUC 0–12 h (994.86 ± 95.79 ng.h/mL) with a minimum lag time compared to oral solution with equivalent dose ( Figure 2 ).…”

“… Development of rizatriptan loaded hydrogel-based mucoadhesive buccal film and enhanced buccal permeation displayed by the film compared to oral solution containing equivalent dose (adapted from [ 25 ], published by MDPI, 2021). *, Statistically different at p < 0.005.…”

Eudragit®: A Versatile Family of Polymers for Hot Melt Extrusion and 3D Printing Processes in Pharmaceutics

“…These two types of polymers (ERL and ERS), with different permeabilities, are often used together in different proportions to achieve the target specific permeability and the desired rate of intestinal absorption. These polymers, alone or in blends, have been used in pharmaceutics for the development of micro [39,40] and nanoparticles [41][42][43][44], coated tablets [45] and mucoadhesive buccal films [46], among others, mainly to obtain sustained release delivery systems.…”

Multilayer Films Based on Chitosan/Pectin Polyelectrolyte Complexes as Novel Platforms for Buccal Administration of Clotrimazole

“…Buccal films are recognized as easily applicable, microbiologically stable drug dosage forms with good retentivity at the mucosa. Over the last years, numerous scientific approaches dedicated to the development of buccal films as potential platforms for either local [10][11][12] or systemic [13][14][15] drugs have been undertaken. Apart from "traditional" monolayer films, systems with more complex structure have been designed as well, nevertheless, they are predominantly composed of layers of neutral or positive polymers dedicated for incorporation of different active substances or they are "equipped" with an additional layer of water-insoluble material ensuring unidirectional drug release at the application site [11,16].…”