Obtenção de micropartículas contendo dispersões sólidas de praziquantel por spray congealing
[thesis]
Marcela Olaia Machado
Palavras-chave: polietilenoglicol, solubilidade, taxa de dissolução, análise térmica, planejamento fatorial ii ABSTRACT MACHADO, M. O. Obtenção de micropartículas contendo dispersões sólidas de praziquantel por spray congealing. 2011. 120f. Dissertação (Mestrado). Faculdade de Ciências Farmacêuticas de Ribeirão Preto -Universidade de São Paulo, Ribeirão Preto, 2011. Schistosomiasis is a parasitic disease caused by the worm Schistosoma mansoni. Its prevalence in Brazil is around 10 million
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... ed people. Treatment is done with praziquantel, an antihelmintic drug both for human and animal use. As it is a class II drug of low solubility and high permeability according to the Biopharmaceutics Classification System (BCS), it is highly valuable to perform a study to improve the solubility and dissolution rates of praziquantel. That is the aim of the present work. Spray congealing was the technique used to obtain solid dispersions of praziquantel. It consists of atomizing the solution or suspension containing the drug in a melting carrier without the need of organic or aqueous solvents. Solid dispersions and physical mixtures were prepared using polyethylene glycol 6000:praziquantel in proportions 10%, 15%, and 20% of praziquantel, and using polyethylene glycol 6000:sorbitol:praziquantel in proportions 10%, 15%, 20%, and 40% of praziquantel. Solubility tests were performed in each sample. Solid dispersions had a significant increase in solubility rate compared to pure praziquantel. The formulations containing polyethylene glycol 6000 and sorbitol had a significant improvement in solubility rate compared to the ones with polyethylene glycol only (p<0,05). However, during the atomization through spray congealing technique, the formulation acquired sticky characteristics, impairing the success of such technique. Thus, the formulation of polyethylene glycol 6000:praziquantel in concentrations 10%, 15% and 20% of praziquantel was chosen and a factorial design type Box-Behnken was planned, in a total of 15 experiments, to study the parameters: flow of the atomization, flow rate of the dispersion, and the percentage of praziquantel. It was carried out an analysis of the samples of physical mixtures, microparticles, and solid dispersions in each proportion through differential exploratory calorimetry, thermogravimetry, infrared ray and X-ray diffraction. The analysis showed that probably there were no interactions between the drug and the polymer. Flow rate analysis of microparticles presented a level from excellent to tolerable, showing an increase in solubility that ranged from 62.6% to 79% compared to pure praziquantel. The average diameter of the particles ranged from 145 to 215µm, which is a reasonable size to improve solubility and properties of the flow. Microparticles had an increase in dissolution rate of 3.18 times compared to pure praziquantel, 2.3 times in relation to physical mixture of 10%, and 2.14 times in relation to solid dispersion of 10%. Morphological analysis revealed irregular particles with wrinkled surface with small crystals of the drug. Photomicrographs showed that there was agglomeration during spray congealing. The technique exhibited an excellent efficacy of encapsulation that ranged from 88% to 108%. Variance analysis for the studied factors showed that only solubility and particle size exhibited values with significant statistical difference. For solubility, the lower the percentage of praziquantel in the sample, the higher the increase in solubility. For particle size, the higher the flow of dispersion, the bigger the particle. From the study carried out, it can be concluded that spray congealing is an efficient, quick and promising technique for preparation of solid dispersions. Key -words: polyethylene glycol, solubility, dissolution rate, thermal analysis, factorial desi ALBERTINI, B.; MEZZENA, M.; PASSERINI, N.; RODRIGUEZ, L.; SCALIA, S. Evaluation of Spray Congealing as Technique for the Preparation of Highly Loaded Solid Lipid Microparticles Containing the Sunscreen Agent, Avobenzone. Journal of Pharmaceutical Sciences v. 98; p. 2759 -2769; 2009. ALBERTINI, B.; PASSERINI, N.; PATTARINO, F.; RODRIGUEZ, L. 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doi:10.11606/d.60.2011.tde-28042011-112616
fatcat:2zjw3rg67fbkbk5s2kbhb7ohom