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

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.

Optimization and physicochemical properties of nutritional protein isolate from pork liver with ultrasound‐assisted alkaline extraction

“…Denatured protein molecules will aggregate and/or crosslink to form larger clusters and, at high concentrations, will result in the formation of crosslinked amino acids such as lysinoalanine, ornithinoalanine, lanthionine and so on. In particular, ultrasound has been commercially used in different food science applications such as emulsification (Kara et al 2015), dispersion of solids (Pereira et al 2016), crystallization (Sheikh & Patel 2014), acceleration of mass transport processes in mixing (Ozuna et al 2013) and extraction (Dahmoune et al 2015;Kadam et al 2015). As a result, new safe and effective methods of food processing and preservation are being developed.…”

“…Acoustic waves can be applied to materials in the form of low intensity waves to passively monitor physical changes in the material caused by non-acoustic sources; or as high intensity waves where disruption of molecular entities or changes in the physicochemical characteristics of the materials are originated. In particular, ultrasound has been commercially used in different food science applications such as emulsification (Kara et al 2015), dispersion of solids (Pereira et al 2016), crystallization (Sheikh & Patel 2014), acceleration of mass transport processes in mixing (Ozuna et al 2013) and extraction (Dahmoune et al 2015;Kadam et al 2015). For the food industry, ultrasound technology could be of significant interest, as it allows 'green' chemistry to be conducted, that is conducting chemical reactions using environmentally benign solvents and reactants (Mahmoodi et al 2010).…”

Construction of mathematical model of dissolution process of solids under action of ultrasound

“…In [10] the influence of ultrasonic irradiation is studied at a frequency of 19 kHz and power of 475 W on solid dispersion and increase of the solubility of insoluble drugs in water. Reduction of ferric iron (Fe 3+ to ferric iron (Fe 2+ ) at zinc production is carried out using ultrasound.…”

Heat and Mass Transfer Remote Control in Bioreactors of Technological Lines

“…Стендові випробування підтверджують доцільність цього способу як такого, що забезпечує і тепломасообмін, і зміну концентрації проникаючої звукової хвилі та розвиток турбулентності в певних межах і зон помірної активності культуральної рідини [6]. Крім того, цей спосіб дає можливість дистан-ційно і безконтактно надавати необхідну кінематичну структуру робочій рідини під час технологічного процесу [7]. До таких переваг слід віднести формований дистанційно потужний глобальний рушійний висхідний потік, який інтенсивно обмиває придонні шари та циліндричну поверхню біореактора.…”