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Mucoadhesive multiparticulate patch for the intrabuccal controlled delivery of lidocaine.

Cavallari C, Fini A, Ospitali F.

Eur J Pharm Biopharm. 2013 ;83(3):405-14.

Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy.

 

Abstract

The aim of the present study was to prepare and evaluate patches for the controlled release of lidocaine in the oral cavity. Mucoadhesive buccal patches, containing 8 mg/cm(2) 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, different type Methocel) 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 with free lidocaine, was also examined to prolong the drug release. The effects of the composition were evaluated considering a number of technological parameters and the release of the drug. All the formulations tested offer a variety of drug release mechanisms, obtaining a quick or delayed or prolonged anesthetic local activity with simple changes of the formulation parameters.

Copyright © 2012 Elsevier B.V. All rights reserved.

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Additional Information: 

Bi-layered mucoadhesive buccal patches, containing 8 mg/cm2 lidocaine base, were formulated to controlled the release of lidocaine in the oral cavity, using the solvent casting method technique, with different semi-synthetic and synthetic polymers (Carbopol, Poloxamer, different type Methocel) and plasticizers (PEG 400, triethyl citrate).

All the patches displayed a notable bioadhesion, necessary for prolonging the residence of the film on the buccal mucosa. Absorption of the drug through a model mucosa occurred without problems, while the presence of a second layer of ethylcellulose provided unidirectional release.

The novelty of the present formulation was the use of lidocaine/Compritol solid dispersion in the form of microspheres, embedded inside the patch.

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.  The presence of lidocaine as solid dispersion allowed a prolonged release of the drug that is completed in 3 h, since the release suffers a second control, after that of the patch gel. 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. 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. To verify this idea we tested a formulation, where a fraction (10%) of free lidocaine was directly added to the gel, while the remaining part (20%) was added as microspheres. In this case the first portion of the profile increased with respect to previous formulation (80% in 30 min); the remaining 20% was released in 3 h.

SEM photos (see Figure) show that the microparticulate fraction contains agglomerates, where different-sized spheres appear wrapped by a network of filaments, responsible of the aggregation. Raman microspectroscopy of these formations revealed that they contain amorphous material.

On the surface of the spheres only Compritol was detected by its spectrum; whereas lidocaine, though present at 30% w/w, does not display distinctive peaks, but wide bands related to its amorphous structure and dissolution inside the Compritol mass. These aspects make the microsphere-embedded patch unexpectedly complex and subject to further modifications and improvements.

 

Figure – SEM photo of the microspheres embedded inside the patch.

Microsphere-loaded mucoadhesive patches