Naslov
Mucoadhesive wafers loaded with econazole-cyclodextrin complexes for treatment of oral candidiadis

Autori
Jug, Mario ; Kosalec, Ivan ; Meninni, Natascia ; Orlandini, Serena ; Furlanetto, Sandra ; Mura, Paola

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts / Šrukelj, Borut - Ljubljana, 2014, 135-136

Skup
10th Central European Symposium on Pharmaceutical Technology

Mjesto i datum
Portorož, Slovenija, 18.09.2014. - 20.09.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
mucoadhesion; buccal drug delivery; econazole; cyclodextrins

Sažetak
Candidosis is one of the most common fungal infections of the oral cavity in humans, caused by yeasts of the genus Candida. Its clinical aspects run from relatively trivial conditions, such as oral thrush, up to systemic super-infections in immuno-compromised patients, with mortality of 30-50%. Despite the availability of several effective antimycotics for the treatment of oral candidosis, failure of the therapy is not uncommon, due to the unique properties of the oral cavity, where both the saliva flushing and the oral musculature cleansing action tend to reduce the local drug concentration to sub-therapeutic levels. Therefore, the aim of this work was to develop a lyophilized wafer formulation based on mixtures of low methylester amidated pectin (LMAP) and carboxymethylcellulose (CMC), which applied to the oral mucosal surface, should allow a prolonged residence time and a controlled release of econazole nitrate (ECN). To overcome the problems of low ECN solubility, the drug was loaded as a ternary complex with sulphobutyl-β-cyclodextrin (SBEβCD) and citric acid (CA). Wafers were prepared by freeze-drying of different hydrogels based on LMAP and CMC mixtures, loaded with ECN at 0.1% w/w, added as co-ground product with SBEβCD and CA. Experimental design methodology was applied to optimize the wafer composition, maximizing its mucoadhesive properties, evaluated "ex vivo" in terms of residence time and mucoadhesive strength to excised porcine mucosa. Drug release studies in simulated saliva were performed on the optimized formulation by using an open-compartment dissolution apparatus to maintain sink conditions.To evaluate the therapeutic potential of the optimised formulation, the time-kill assay was performed with C. albicans ATTC 90028 and C. krusei ATTC 6258 as model fungal strains. The optimized wafer formulation was added to the inoculum suspension in the liquid nutrient medium, and the viability of Candida strains was monitored as a function of time using mitochondrial dehydrogenase activity assay.A product with the desired and predicted quality was developed using the experimental design. The examined formulation variables were amidation degree of LMAP and concentrations of LMAP and CMC. Their influence on mucoadhesive strength, in situ residence time and % of drug released at a given time, chosen as the responses indicative of the system performance, were examined by an initial screening design. This enabled identification of the variables influencing on the considered responses, and determination of their best levels for the response optimization. A response surface study was then performed, to investigate in depth the values of the responses for all possible combinations of the factors selected in the previous screening phase. The desirability function allowed finding the optimal wafer composition: LMAP 7.2 % (w/w) and CMC 5.2% (w/w). The experimental values of adhesive strength (28.4 ± 0.04 g/cm2) and residence time (88.1±0.1 min) given by the optimized formulation were very close to the predicted values, demonstrating the validity of the applied model. The optimized wafer formulation showed an appropriate and controlled drug release (Fig.2), of about 5 mg/h, during the observed residence time on the mucosa surface, thus enabling the maintenance of therapeutic ECN levels during the whole wafer application time. Finally, the analysis of the antimycotic activity of the optimized ECN wafer formulation (Fig. 3) demonstrated its good potential as a novel effective topical delivery system able to improve the existing therapy of oral candidosis.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

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