Pilot Formulation Study of Ph-sensitive Gels

Abstract

Drugs remain for a short time on mucus membranes, such as oral, ocular, or nasal mucus, which are washed with physiological fluids. One of the possibilities to overcome this obstacle is the application of solutions that, due to the physiological environment or stimulus, turn into more viscous gels. These gels often also have mucoadhesive properties and the drug is released from them for a longer period. Carbomer 940 (C940), polycarbophil (PCP), and chitosan (CH) are gel-forming excipients, and the consistency of their solutions changes due to the concentration of protons (pH); therefore, they are referred to as pH-sensitive gelling agents. The aim of this study was to prepare pH-sensitive solutions that form gels in the pH of the oral cavity. We prepared water solutions with various concentrations of gel-forming excipients and evaluated the appearance, pH of the solution, injectability of the solution, and pH of gelation. By determining the pH of gelation, suitable concentrations (w/w) of the used polymers were found, namely, 0.1% C940, 0.225% PCP, and 2.5% CH with medium molecular weight (CHM). The 0.1% C940 and 0.225% PCP solutions were injectable through the syringe with the smallest 0.5 mm needle diameter. The 2.5% CHM solution was not injectable even through the syringe with the largest 0.8 mm needle diameter. Solgels prepared at the determined concentrations were evaluated by a dissolution test in a pH 6.8 phosphate buffer using methylene blue (MB) as a model substance. After 60 min of dissolution, 77.04% ± 5.94%, 48.85% ± 5.74%, and 77.35% ± 4.98% of MB were released from samples with C940, PCP, and CHM, respectively. The dissolution of the C940 and CHM samples took place according to the Korsmeyer–Peppas kinetic model (R2 0.999 ± 0.001, 0.978 ± 0.003) and of the PCP samples took place according to the first-order model (R2 0.994 ± 0.001). The 0.225% PCP pH-sensitive gel showed the most advantageous properties in terms of injectability, pH gelation, and prolonged release of MB.

Keywords

• in situ
• ph-sensitive
• gel
• polycarbophil
• chitosan
• carbomer 940