Ultrasound influence on the solubility of solid dispersions prepared for a poorly soluble drug

• Published in: Ultrasonics sonochemistry Vol. 29; pp. 461 - 469
• Main Authors: Pereira, Simone Vieira, Colombo, Fábio Belotti, de Freitas, Luis Alexandre Pedro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2016
• Subjects: Dissolution rate; Drug Carriers - chemistry; Piroxicam; Piroxicam - chemistry; Solubility; Sonication; Temperature; Time Factors; Ultrasound; Water - chemistry; Piroxicam; Dissolution rate; Ultrasound; Solubility
• ISSN: 1350-4177; 1873-2828
• DOI: 10.1016/j.ultsonch.2015.10.022

•First work to evaluate the ultrasound effect on pharmaceutical solid dispersions.•Use of multivariate analysis to evaluate ultrasound parameters.•Complete microparticle characterization by dissolution and solid state analysis.•Revealing the importance of ultrasound conditions to drug solubility.•Expressive solubility enhancement by adequate ultrasound use. 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 13.3μg/mL. A maximum fourfold increase in solubility, reaching 53.8μg/mL, was observed for a solid dispersion sonicated at 19kHz for 10min and 475W. 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.