Poor solubility and low dissolution rate of drug substances are two major challenges in the pharmaceutical industry, therefore, many approaches are being developed to improve them, including nanotechnological ones (e.g., nanofiber fabrication). The aim of this Master's thesis was to develop bioadhesive polymer nanofibers with prolonged carvedilol release. According to the biopharmaceutical classification system, carvedilol belongs to class II drugs with poor solubility and good permeability. By electrospinning we produced smooth thin polymer fibers, with nanosized diameter and with some irregularities in the structure. A hydrophilic polymer with bioadhesive properties, namely polyvinylpyrrolidone K90, was used as a key building block for the production of nanofibers. The water-insoluble polymer Eudragit® RL PO was added to the nanofiber formulation to achieve prolonged drug release. We added it in different amounts. We have shown that higher amount of Eudragit® RL PO in the formulation results in the slower carvedilol release. By incorporation of carvedilol into nanofibers, we wanted to increase its solubility. We performed the solubility test to examine the effect of the delivery system on the solubility of the active ingredient compared to its solubility in a form of physical mixture with the same composition. The solubility of carvedilol was increased ~ 8-times by polyvinylpyrrolidone K90 nanofiber formulation and ~ 4-times by nanofiber formulation with Eudragit® RL PO. By nanofiber formulation, we achieved also supersaturation state, which lasted throughout the test (26 h). We evaluated the bioadhesive potential of nanofiber formulation by rheological measurements, thus we performed rotational experiments with a controlled shear rate. Rotational experiments were used for investigating of interactions between the polymers and commercially available mucin from porcine stomach (type II). Positive rheological synergism was calculated for both polymers, namely polyvinylpyrrolidone K90 and Eudragit® RL PO when combined with a mucin solution, which indicates mucoadhesive properties of both polymers. Based on the obtained results, we can conclude that nanofibers based on polyvinylpyrrolidone K90 and Eudragita® RL PO also have mucoadhesive properties. In further research, it would be worth to explore the mucoadhesive properties of nanofibers by a suitable direct method and, based on the results obtained, to optimize the formulation in order to achieve adequate strength and duration of adhesion.
|
