Solid dispersions enhanced nystatin solubility without significant improvement in permeability: Potential application in localized therapies

This study aimed to develop solid dispersions of nystatin using different carriers to enhance its solubility, impart mucoadhesive properties, and reduce permeability, aiming at local action in the buccal cavity. 1, 2 and 3 generation of NYS SD were developed, employing lactose, hydroxypropylmethylcellulose (HPMC), poloxamer 407 (P407) and poloxamer 188 (P188) as carriers. NYS SD were characterized by differential scanning calorimetry and thermogravimetry/derivative thermogravimetry. Further characterization was conducted with NYS SD that showed a specific thermal behavior suggesting the formation of a new system by solubility, power X-ray diffraction, Fourier transform infrared spectroscopy, and parallel artificial membrane permeability assay. The results demonstrated the feasibility of developing a 3 NYS SD system with enhanced solubility compared to raw NYS in water (4.484 mg/mL); at pH 5.5 (4.249 mg/mL) and pH 7.0 (4.293 mg/mL), making it more readily available in saliva and, consequently, within the oral cavity. Moreover, the in vitro permeation test did not show a significant increase in permeation, reinforcing the potential of the formulation for local action. In conclusion, NYS SDs were developed using a low-cost, reproducible rotary evaporation method and hydrophilic carriers, with F8—based on poloxamer 188—showing the most promising results. F8 exhibited a fourfold increase in aqueous solubility without altering mucosal permeability, addressing NYS's poor solubility, which may compromise its therapeutic efficacy. As a safe antifungal, NYS is a strong candidate for formulation strategies that enhance solubility. These findings support the continued investigation of F8 as a topical treatment for oral candidiasis.