Mucoadhesive film and PLGA based nanoparticle as carrier systems for sublingual delivery of Glutathione

Abstract

The sublingual mucosa provides a promising route for the delivery of active pharmaceutical ingredients (APIs). However, challenges are encountered in developing sublingual mucoadhesive drug delivery formulations, with regard to the achievement of prolonged drug retention, uniform drug content, desirable drug release profile, adequate drug permeation and efficient delivery of APIs. These challenges limit the number of commercially available sublingual mucoadhesive products. To overcome these problems, which is also the aim of this study, a mucoadhesive polymer based sublingual film and PLGA based Water-in-Oil-in-Water (w/o/w) emulsion nanoparticle, the two systems were developed as potential platform technologies, and to optimize the sustained release and abosorption of the Glutathione. Mucoadhesive films were prepared by traditional casting methods using different polymers in order to produce a satisfactory film. Formulation capable of elevation of retention time and resist saliva dissolution, provide protection from degradative buccal enzymes as well as generating a sustained drug release profile are desirable. Among these, mucoadhesion was considered prior to assessing drug release and drug permeation. Several characteristic studies were carried out, including: thickness; weight uniformity; enlongation properties; mucoadhesiveness; swelling erosion properties; rheological properties; in-vitro drug release properties and ex-vivo permeation characteristics of the sublingual films. The optimized mucoadhesvie polymers based films showed good mucoadhesion and remained attached to the human sublingual mucosa for sufficient period of time with least discomfort for patients, as well as with approximately 15% of the loading dose permeating through porcine mucosa from ex-vivo studies. Nanotechnology is a novel delivery system which has been extensively studied for sublingual delivery due to its sustained and targeted release properties, as well as enzymatic degradation prevention characteristics. Nanoparticles loaded with GSH and prepared by the solvent evaporation method of w/o/w emulsions were studied in this paper. Two-level full factorial design was carried out based on different type and concentration of stabilizers used, and different sonication time to evaluate on particle size, zeta-potential and entrapment efficiency in order to generate the optimized formulation. More sustained release profile was achieved with nanoparticles loaded with GSH, as compared to sublingual films, but lower in drug permeation percentage across the porcine mucosa tissue. Approximately 2-fold increase in the transmucosal permeation of GSH was achieved when permeation enhancer (chitosan) was incorporated within the nanoparticle system. However, when the optimized nanoparticle suspensions casted to the selected optimized mucoadhesive films, the combination of the systems did not improve the permeability in ex-vivo studies, thereby suitable permeation enhancers should be included in the future studies. In summary, two novel delivery systems mucoadhesive films and nanoparticles were developed. Important information was generated pertaining to the influence of a range of variables on the overall quality, the drug release manner and the drug permeation properties. Thus the two systems may provide a promising drug delivery platform to develop commercial sublingual products of GSH as well as a wide range of APIs.