Ultrasound influence on the solubility of solid dispersions prepared for a poorly soluble drug |
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| Institution: | 1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Núcleo de Pesquisa em Produtos Naturais e Sintéticos – Universidade de São Paulo, Via do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil;2. Escola Politécnica, Universidade de São Paulo, 05508-010 São Paulo, SP, Brazil;1. Gedeon Richter Plc, Pharmacology and Drug Safety Department, Budapest, Hungary;2. MTA SE NAP B Cognitive Translational Behavioral Pharmacology Group, Budapest, Hungary;3. MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, Hungary;4. Institute of Pharmaceutical Chemistry and Stereochemistry Research Group of the Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary;5. Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary;6. Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary;1. Servicio de Cardiología, Hospital Universitario de León, León, España;2. Servicio de Cardiología, Hospital Clínico Universitario, CIBERCV, Valladolid, España;3. Servicio de Cardiología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, España;4. Servicio de Cardiología, Hospital Universitario Reina Sofía, Universidad de Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, España;1. Neurodegeneration and Pain Unit, Sanofi R&D, Chilly-Mazarin, France;2. Disposition, Safety and Animal Research, Sanofi R&D, Montpellier, France;3. Translational Sciences Unit, Sanofi R&D, Chilly-Mazarin, France;1. College of Industrial Technology, Nihon University, 1-2-1 Izumi-cho, Narashino, Chiba 275-8575, Japan;2. Faculty of Engineering, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan |
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| Abstract: | Solid dispersions have been successfully used to enhance the solubility of several poorly water soluble drugs. Solid dispersions are produced by melting hydrophilic carriers and mixing in the poorly water soluble drug. Supersaturation is obtained by quickly cooling the mixture until it solidifies, thereby entrapping the drug. The effects of using ultrasound to homogenize the molten carrier and drug mixture were studied. In particular, the increase in drug solubility for the resulting solid dispersions was analyzed. Piroxicam, which has very low water solubility, was used as a model drug. A full factorial design was used to analyze how sonication parameters affected the solubility and in vitro release of the drug. The results show that the use of ultrasound can significantly increase the solubility and dissolution rate of the piroxicam solid dispersion. Pure piroxicam presented a solubility of 13.3 μg/mL. A maximum fourfold increase in solubility, reaching 53.8 μg/mL, was observed for a solid dispersion sonicated at 19 kHz for 10 min and 475 W. The in vitro dissolution rate test showed the sonicated solid dispersion reached a maximum rate of 18%/min, a sixfold increase over the piroxicam rate of 2.9%/min. Further solid state characterization by thermal, X-ray diffraction and Fourier transform infrared analyses also showed that the sonication process, in the described conditions, did not adversely alter the drug or significantly change its polymorphic form. Ultrasound is therefore an interesting technique to homogenize drug/carrier mixtures with the objective of increasing the solubility of drugs with poor water solubility. |
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| Keywords: | Piroxicam Ultrasound Solubility Dissolution rate |
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