In Vitro and In Vivo Characterisation of a Mucoadhesive Buccal Film Loaded with Doxycycline Hyclate for Topical Application in Periodontitis

Abstract

Mucoadhesive films loaded with doxycycline hyclate (Doxy Hyc), consisting of mixtures of hydroxypropylmethyl cellulose (HPMC) E3, K4 and polyacrylic acid (Carbopol 940), were prepared by casting method, aiming to design a formulation intended for application in the oral cavity. The obtained film formulations exhibited a Doxy Hyc content between 7.52 ± 0.42 and 7.83 ± 0.41%, which had adequate mechanical properties for application in the oral cavity and pH values in the tolerance range. The x-ray diffraction studies highlighted the amorphisation of Doxy Hyc in the preparation process and the antibiotic particles present on the surface of the films, identified in the TEM images, which ensured a burst release effect in the first 15 min of the in vitro dissolution studies, after which Doxy Hyc was released by diffusion, the data presenting a good correlation with the Peppas model, n < 0.5. The formulation F1, consisting of HPMC K4 combined with C940 in a ratio of 5:3, the most performing in vitro, was tested in vivo in experimentally-induced periodontitis and demonstrated its effectiveness in improving the clinical parameters and reducing the salivary levels of matrix metalloproteinase-8 (MMP-8). The prepared Doxy Hyc loaded mucoadhesive buccal film could be used as an adjuvant for the local treatment of periodontitis, ensuring prolonged release of the antibiotic after topical application.

Optimization of a Mucoadhesive Vaginal Gel Containing Clotrimazole Using a D-Optimal Experimental Design and Multivariate Analysis

“…The increase in the amount of CLT released, as well as the rate of CLT released in the case of formulations based on PEO 750 , is explained by the faster disintegration of the formulation in water, since PEO 750 has a lower degree of polymerization and forms gels with lower viscosity. These results are also reflected by the higher "n" values, indicating zero-order release and suggesting that the release of CLT is controlled by the erosion of the gel matrix [33]. The average size observed for the suspended CLT particles was 5.24 ± 0.57 µm, which allows the homogeneous dispersion of CLT in the gel matrix, optimal dissolution in vaginal secretions, and a lack of irritation phenomena.…”

“…To evaluate the mechanism of kinetic release of CLT from the dosage form, correlation coefficients (R 2 ) and release rate constants (K) for various models (Korsmeyer-Peppas, Higuchi, first-order, and zero-order model) were determined for all studied CLT-MVG formulations [33]. The mathematical models were fitted to individual dissolution data with the regression module of SigmaPlot 8.…”

“…The Peppas model generated n-values in the range of 0.6946-0.8536, indicating that the release of CLT follows a non-Fickian behavior, in which the diffusion phenomena from the three-dimensional network structure of the gel are over-imposed on the swelling ones. The zero-order release behavior may suggest that the release of CLT was controlled by the erosion constant of the matrix [33]. The thixotropy index (Y3) increased with increasing amounts of C 940 and PEO 1105 in the formulation, while PEO 750 had a negative influence.…”

Filmes mucoadesivos na saúde

“…Estes autores formularam um filme multicamada composto por QT e pectina, com objetivo de entrega controlada do antifúngico clotrimazol, com resultados que indicam aplicação promissora para tratamento de candidíase oral. Já Dinte et al (2023) produziram filmes de uma camada carregados com hiclato de doxiciclina, em uma associação polimérica de hidroxipropilmetilcelulose (HPMC) e ácido poliacrílico com objetivo de projetar uma formulação destinada à aplicação em cavidade oral, e seus resultados indicaram o filme carregado com hiclato de doxiciclina como opção favorável como adjuvante no tratamento local de periodontite, garantindo liberação prolongada do antimicrobiano após aplicação local.…”