Jordan Journal of Pharmaceutical Sciences, Volume 2, No. 1, 2009 - 32 - Dissolution Enhancement of Poorly Water Soluble Drugs by Co-precipitation in the Presence of Additives and Stabilizers Mai Khanfar 1 and Mutaz Sheikh Salem 2 1 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman, Jordan. 2 Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology (JUST), Irbid, Jordan. ABSTRACT Mefenamic acid and Astemizole are models of drugs with poor aqueous solubility. The dissolution rates of Mefenamic acid and Astemizole were enhanced by the precipitation of both drugs in the presence of aqueous surfactant (SAA) (Cremophor®) and polymer solution (PEG 20,000). The highest dissolution rate for both drugs was achieved by precipitation in the presence of (Cremophor®), followed by precipitation in the presence of (PEG 20,000). The precipitated crystals were characterized using IR, DSC, SEM and X-ray powder diffraction. Mefenamic acid precipitates were of smaller size with no habit change, while in the case of astemizole there was a decrease in the crystallinity compared with the original powder. No changes in the polymorphic forms for both drugs were noticed during precipitation process. Keywords: Mefenamic acid, Astemizole, precipitation, crystallization. INTRODUCTION Developing novel techniques to improve the dissolution and bioavailability is of great importance in the development of pharmaceutical formulations, particularly those containing an active ingredient that is poorly soluble in water 1 . A common method for increasing the dissolution rate is forming of a high specific surface area by micronization. The process is usually used to obtain small particles by the disruption of large crystals. Chaumeil describes the improvement in dissolution rate and in bioavailability by micronization of sparingly water-soluble drugs using jar mills and fluid energy mills 2 . Cospite and Dominici 3 describe a better clinical efficacy for micronized diosmin compared with the nonmicronized drug. However, several disadvantages resulting from the preparation process exist. In this context, the micronization process using mills is extremely inefficient 4 . Because high energy input can induce disruptions in the crystal lattice which can lead to physical or chemical instability. In addition, disordered regions in the resulting product are thermodynamically unstable. Ticehurst et al. 5 describe a method of micronizing revatropate hydrobromide in a jet mill. Disordered structures were detected and analyzed by dynamic vapor sorption analysis. Amorphous or disordered material will recrystallize, especially when water from the atmosphere is adsorbed. Because of a reduction of the glass transition temperature, the energy threshold to recrystallization is decreased 6 . The conversion of crystalline solid surfaces into partially amorphous solid surfaces leads to a dynamic nature of the micronized drug 7 . In addition to this, Received on 22/4/2008 and Accepted for Publication on 5/8/2008. E-mail: m_khanfar@philadelphia.edu.jo or khanfarmai@yahoo.com © 2009 DAR Publishers/University of Jordan. All Rights Reserved.