Development and characterization of biodegradable microparticles based on natural mucoadhesive polymers and miconazole nitrate

LEONARDI, D.; TEJADA, G.; ALVAREZ, V. A.; LAMAS, M. C.

Mar del Plata

Congreso; XVI Simposio Latinoamericano de Polimeros; 2018

INTRODUCTIONMiconazole nitrate (MN) is an antifungal drug widely used to treat topical fungal and yeast infections. Traditional oral topical antifungal therapies have many limitations, including short contact time with the oral mucosa and the requirement to administrate various doses per day. The aim of this work was to develop and to characterize polymeric microparticulated systems loaded with MN as an alternative therapeutic system for the treatment of oral candidiasis.1 EXPERIMENTAL METHODSMicroparticulated system based on cationic, anionic and non ionic polymers and their combinations were obtained spraying polymeric solutions (Buchi Mini dryer B-290, Flawil, Switzerland). Polymeric Solutions: Chitosan (CH) (0.1% w/v in acetic acid), Gelatin (GEL) and Hydry-propyl-methylcellulose (HPMC) water solutions (0.1% w/v) were prepared, after that MN 70% w/w was added to each polymeric solution. Mixtures were dried in order to obtain the microparticulated systems. 2 Dissolution studies were performed. The amount of released MN was determined by UV spectrometry (272 nm). Morphology and particle size of raw MN and microparticles were investigated by scanning electron microscopy (SEM). Additionally, Fourier-transform infrared spectroscopy, and thermal analysis (TGA and DSC) of MN, polymers, loaded and empty microparticles were employed to the analysis. In vitro halo zone test was performed. C albicans (ATCC 10231) was cultured in Sabouraud´s dextrose agar 24 h before testing. The plates were incubated in air at 28 °C and read at 24 h. Halo diameters for the zone of complete inhibition were determined using a caliper and the mean value for the organism was recorded.1RESULTS AND DISCUSSIONMicroparticles based just on HPMC showed fastest drug release, reaching almost 100% after 30 minutes. Oppositely, systems based just on GEL or CH released lower amounts of MN: 10.2% and 13.2% of MN respectively, while systems based on combinations of polymers showed releases in a range between 35 and 44%.DSC curve of microparticles containing MN shows that the microencapsulation process did not affect the polymer structure because the pure polymer presented the same value for relaxation enthalpy. DSC curves did not detect any crystalline drug material in the MN-loaded nanoparticles samples; the endothermic peak of MN was absent. Thus, the drug incorporated into the microparticles was in an amorphous or disordered-crystalline phase of a molecular dispersion or a solid solution state in the polymeric matrixAfter analysing the halo zone test systems based on CH-HPMC and CH-GEL were able to produce greater inhibition halos after six and seven hours assay. CH produced smaller halos at the beginning of the assay, because the matrix was unable to swell in the medium, and, a lower content of MN was exposed to the culture. Halos around 20 mm were observed after 7 hours assayed while MN raw material produced smaller halo (3 mm). At this point, MN halo was closer to the produced by the microparticles based on GEL. Thus, these results showed that the microencapsulation of MN in CH-GEL matrix allow sustain the activity of the drug controlling the exposure of MN.CONCLUSIONThe manufacturing procedure and the polymers produced a protective effect on the drug and indeed the drug is mainly in the amorphous phase or disordered-crystalline phase in the polymeric matrix. This issue enhances the solubility and the dissolution process of miconazole nitrate loaded in the microparticles, proving promising characteristics to further formulate oral topic systems.The in vitro activity analyzed by the halo zone text experiments showed that microparticles based on oppositely charged polymers presented a drug control release improving the activity versus the time.