Influence of the ethanol/dichloromethane ratio on the preparation of microsponges composed of ethylcellulose and Eudragit or HPMCphthalate for hydrophilic drug delivery

Abstract

Microsponges (MS) have shown great potential for the incorporation of relatively higher amounts of drugs. This is due to the presence of both surface pores and interconnected channels that provide a greater contact area for the absorption of active agents. However, the use of MS for carrying hydrophobic drugs is limited because the preparation methodology can totally remove hydrophilic drugs. Therefore, this work aimed to investigate possible changes in the proportion of organic solvents used to produce MS containing water-soluble drugs. A modified quasi-emulsion solvent diffusion technique was used to formulate MS with ethylcellulose and Eudragit RS 100 (MS-EE) or ethylcellulose and HPMCphthalate (MS-EH) using different combinations of ethanol/dichloromethane ratios. The effects of the polymeric composition and organic solvent ratio were evaluated on the morphology, size, swelling, yield, drug content, entrapment efficiency and in vitro release of methylene blue (MB), a hydrophilic drug model. Both polymer combinations resulted in spherical and porous particles. MS-EE was larger (8–13 μm) and displayed higher product yield (62–77%), but MS-EH showed a higher drug entrapment (11–41%), which was higher with an increase in the amount of ethanol amount used. Only MS-EH displayed in vitro MB release during 24 h (70%). ATR-FTIR and FT-Raman analyses did not demonstrate chemical interactions between MB and the polymers. Differential scanning calorimetry, thermogravimetry, and x-ray diffraction confirmed the molecular dispersion of MB in the MS polymer matrix. Ex vivo permeation studies by Franz cells and photoacoustic spectroscopy showed that MB could diffuse out from the polymer matrix and permeate both pig skin and mucosa. The particles were shown to be good carriers for MB and they provided controlled drug release and permeation through skin and mucous tissue; however, the MS particles themselves are not able to permeate these membranes. The use of ethanol in the solvent system constitutes a good strategy to obtain MS of ethylcellulose and HPMCphthalate for delivery of MB and suggests that MS is worthy of investigation as carrier for delivery other hydrophilic drugs.