Efficient approach to enhance drug solubility by particle engineering of bovine serum albumin

Abstract

Please cite this article as: Khoder, Mouhamad, Abdelkader, Hamdy, ElShaer, Amr, Karam, Ayman, Najlah, Mohammad, Alany, Raid G., Efficient approach to enhance drug solubility by particle engineering of bovine serum albumin.International Journal of Pharmaceutics http://dx.doi.org/10. 1016/j.ijpharm.2016.11.019 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

The use of albumin solid dispersion to enhance the solubility of unionizable drugs

“…In a recent study, we demonstrated the possible use of BSA as solubility enhancer for indomethacin as ionisable drugs model, where the solubility was improved up to 10 5 times after formulating it in BSA solid dispersion (Khoder et al, 2016). This spectacular solubility enhancement was mainly attributed to the formation of salts bridges between indomethacin carboxylate groups and BSA amino groups.…”

“…Unionisable drugs are not expected to form salts with BSA molecules, yet they might bind to albumin molecules and form a reversible drug-albumin binding complex of higher solubility (Ghuman, Zunszain, Petitpas, Bhattacharya, Otagiri andCurry 2005, Urien, Tillement andBarré 2007). Additionally, converting the drug into a molecular and/or amorphous state that is homogeneously dispersed within the hydrophilic matrix provided by BSA might actively contribute in the enhancement of drug solubility and dissolution rate (Graeser et al 2010, Hancock and Zografi 1997, Huang and Dai 2014, Khoder et al, 2016. PRD:BSA solid dispersions were obtained using two different particle engineering technologies; spray-drying and freeze-drying.…”

“…An enhancement factor of 100,000 was obtained after formulating indomethacin in BSA solid dispersions. The solubility enactment of indomethacin in presence of BSA is thought to be mainly due to the formation of salt bridges between the drug and the albumin molecules (Khoder et al 2016). However, the solubilizing properties of albumin are not limited to its ability to form salts with ionisable molecules but also to its remarkable ability to form reversible binding complexes with hydrophobic drugs (Ghuman et al 2005, Urien et al 2007.…”

“…Bovine serum albuin (BSA) has been widely used in numerous pharmaceutical and medical applications thanks to its stability, biocompatibility and low immunogenicity (Elzoghby et al 2012, Khoder et al, 2016. The aim of this study is to investigate the potential use of the BSA to enhance the solubility of the unionisable drugs using PRD as a model drug.…”

Effects of Solvents, Emulsions, Cosolvents, and Complexions on Ex Vivo Mouse Myometrial Contractility

“…The most common pharmacological approaches to solubilize poorly water-soluble compounds include surfactant addition, cosolvency, and complexation [4,18,19]. We explored the effects of the common surfactants Tween 80, Triton X-100, vitamin E TPGS, and Cremophor EL at concentrations of 0.03125-0.5% v/v in an effort to fully or partially solubilize nifedipine, a water-insoluble compound that is clinically utilized as a tocolytic.…”