Mucoadhesive microparticulate-loaded films for the intrabuccal delivery of lidocaine

Aim The present study was carried out to prepare and evaluate bioadhesive films for the controlled release of lidocaine in the oral cavity. Methods Bi-layered mucoadhesive buccal patches, containing 8 mg/cm2 lidocaine base, were formulated and developed by solvent casting method technique, using a number of different bio-adhesive and film-forming semi-synthetic and synthetic polymers (Carbopol, Poloxamer, Methocel® E50P, K4M, K15M) and plasticizers (PEG 400, triethyl citrate); the patches were evaluated for bioadhesion, in vitro drug release and permeation using a modified Franz diffusion cell. A lidocaine/Compritol solid dispersion in the form of microspheres, embedded inside the patch, alone or together free lidocaine, was employed to prolong the drug release. This type of formulation was further studied employing SEM and thermal (DSC) as well as spectroscopic (RAMAN) analysis. Results Differences among the three types of HPMC expressed in terms of 50% release of lidocaine from the patches as a function of time are: K15M (15 min) < E50P (20 min) < K4M (40 min) and confirm that the ability of water to diffuse into the gel, formed by hydration of the polymer chain inside the patch is lower for the gel formed by K4M than for the other types HPMC. When lidocaine is loaded together HPMC the release is faster and complete after 40 min. Electrostatic interactions between oppositely charged functional groups of lidocaine and Carbopol are responsible of the slowed release. Plasticizers impart flexibility to the polymer film: triethyl citrate and PEG, with different solubility in water, provide an increase of hydration of the film and a decrease of the gel-forming temperature, allowing a quick release of the drug. Absorption of the drug through a model mucosa occurs without problems, while the presence of a second layer of ethylcellulose provides unidirectional release. Lidocaine was also loaded as solid dispersion with Compritol, in the form of microspheres embedded inside the patch. The association of a drug with a lipophilic carrier, such as Compritol 888ATO, is expected to increase the resistance of the system to release the drug, since the release of the lidocaine suffers a second control, after that of the patch gel. The lidocaine release profile from these systems offers unexpected results: first, the release profile shows two distinct and linear portions, suggesting a bimodal mechanism of release. The first portion lasts 30 min with 40% of the release; afterwards the release continues with a different slope reaching 100% in 3 h. Second, the first portion of the release profile perfectly overlaps with that of the reference formulation, as if the drug was distributed inside and outside the microspheres. Conclusions Mucoadhesive bilayered patches can be prepared containing lidocaine with modulation of the control mechanism: a prompt release can be obtained by addition of plasticizers; a retarded release was observed using K4M HPMC grade, while an accelerated release was observed when lidocaine is loaded on HMPC rather than Carbopol. Finally the presence of lidocaine as solid dispersion in Compritol allows a prolonged and bimodal release of the drug that is completed in 3 h. References Fini A, Bergamante V, Ceschel GC. Mucoadhesive Gels Designed for the Controlled Release of Chlorhexidine in the Oral Cavity Pharmaceutics, 3:665-679 (2011)