Designing, Characterization, and Optimization of Nystatin Loaded Mucoadhesive Spanlastical Hard Candy Lozenges as a Treatment of Oral Candidiasis: An in-vivo Study on Rats

Abstract

Introduction and Aim: Oral candidiasis is a common infectious disease affecting children and adults who usually receive oral antibiotics or chemotherapy. Optimizing Nystatin administration is challenging due to its poor solubility and systemically non-absorbable nature. In this work, Nystatin Spanlastical-hard candies were prepared for Oro-local application to improve Nystatin’s local antifungal efficacy, contact time, and taste. Methods: Eight Nystatin Spanlastics were prepared using the ethanol injection method via 2 3 factorial designs using Span, edge activator, and bath-sonication time at two levels. They were evaluated visually and examined for EE%, in-vitro release%, P-size, PDI, and Zeta-potential. The optimum formulae were compared to the marketed oral suspension Nystatin ® by conducting an in-vitro antimicrobial study. The formula of the best antifungal activity was incorporated into four batches of hard candies by 2 2 factorial-design using heating and congealing method using corn-syrup and xanthan-gum in two levels of concentration along with other additives. After performing physiochemical evaluation, the optimum formula was subjected to FTIR analysis and an in-vivo study on rats to compare its activity with the selected market formula. The Design-Expert-13 ® and MS-Excel-2010 ® software were used to interpret all results statistically. Results: The optimum Spanlastical formula was Sp3, which is a combination of Span 80 with SDC, and was sonicated for 3 minutes. The optimum lozenges were those of the SP3L1 batch containing the highest Corn syrup and Xanthan gum concentration levels. SP3L1 lozenges showed no interactions between their ingredients within the obtained FTIR spectra. They gave the animal subjects a higher in-vivo antifungal activity with a significant reduction in the colony formation units’ count at P≤ 0.05 than the (Nystatin) marketed oral suspension. The rats also treated with SP3L1 showed very normal oral tissues by the end of the study period compared to those treated with the market oral formula (Nystatin). Conclusion: This preclinical study merged nanotechnology with mucoadhesive lozenging to improve Nystatin’s antifungal activity, oral residence, and ease of administration compared to the traditionally marketed oral suspension. Keywords: Nystatin, candidiasis, spanlastical candy, mucoadhesive lozenges, in-vivo study