Colloids and Surfaces B: Biointerfaces 76 (2010) 170–178 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb To enhance dissolution rate of poorly water-soluble drugs: Glucosamine hydrochloride as a potential carrier in solid dispersion formulations Hiba Al-Hamidi a , Alison A. Edwards a , Mohammad A. Mohammad b , Ali Nokhodchi a,c,∗ a Medway School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK b Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria c Faculty of Pharmacy and Drug Applied Research Center, Tabriz University of Medical Sciences, Iran article info Article history: Received 10 July 2009 Received in revised form 22 September 2009 Accepted 19 October 2009 Available online 11 November 2009 Keywords: Solid dispersion Carbamazepine Glucosamine HCl Type of solvent Polymorphism Dissolution rate abstract The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however this is reliant on a suitable carrier and solvent being selected. The work presented explores d-glucosamine HCl (G-HCl) as a potential hydrophilic carrier to improve disso- lution rate of a poorly water-soluble drug, carbamazepine (CBZ), from physical mixtures and solid dispersion formulations. The effect of different solvents in the preparation of solid dispersion formu- lations was also investigated. Solid dispersions of the drug and G-HCl were prepared using different ratios by the conventional solvent evaporation method. Different solvents (ethanol, acetone and water) were used as second variable in the preparation of solid dispersions. Physical mixtures of CBZ and G- HCl were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, FT-IR, SEM and DSC. These results showed that the presence of glucosamine can increase dissolution rate of CBZ compared to pure CBZ. All solid dispersions of CBZ–G-HCl showed considerably a higher dissolution rate than the corresponding physical mixtures. The presence of water during preparation of the solid dispersions reduced the dissolution rate of CBZ due to formation of carbamazepine dihydrate during the preparation of solid dispersion, as proved by DSC and FT-IR studies. To facilitate comparison, the dissolution efficiency was calculated for solid dispersions prepared with different solvents and the dissolution efficiency can generally be ranked as follows: ethanol > acetone > ethanol–water > acetone–water when the ratios of drug to carrier were 4:1 and 2:1. It has thus been shown that the use of G-HCl in solid dispersion formulations can significantly enhance the dissolution rate of poorly water-soluble drugs such as carbamazepine. This amino sugar could be used as a new carrier in solid dispersion formulations and would have significant commercial potential. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Drugs which belong to class II of the biopharmaceutical clas- sification system (BCS) are characterized by high membrane permeability, slow dissolution rate (due to low aqueous solubil- ity), and high peroral dose [1]. The solubility or dissolution rate of a drug in this category is therefore a key factor in determining the rate and extent of its absorption. Enhancement of the dissolution rate is vital to attain suitable blood concentration for therapeutic effect, as their dissolution rates are typically the rate limiting step for bioavailability. Carbamazepine is an established drug used in the treatment of epilepsy and trigeminal neuralgia [2,3] and is an ∗ Corresponding author at: Medway School of Pharmacy, University of Kent, Cen- tral Avenue, Anson Building, Chatham Maritime, Kent ME4 4TB, UK. Tel.: +44 1634 883846. E-mail address: a.nokhodchi@kent.ac.uk (A. Nokhodchi). ideal example to illustrate the need for improvement of dissolution for class II drugs. Several technological methods have been reported for improve- ment of solubility and dissolution rate of poorly water-soluble drugs, namely (a) reducing particle size to increase surface area; (b) solubilization in surfactant systems; (c) formation of water- soluble complexes; (d) use of prodrug and drug derivatization approach such as strong electrolyte salt forms that usually have higher dissolution rates; (e) manipulation of the solid state of the drug substance to improve drug dissolution, i.e., by decreasing crystallinity of the drug substance through formation of solid solu- tions [4]. The most common method employed for class II drugs is micronization. This technique is disadvantaged by the greater tendency of micronized particles to stick together and make larger agglomerates which in turn leads to a reduction in effective surface area for dissolution [5]. The recent liquisolid technique can be used to improve dissolution rate of poorly water-soluble drugs [6,7], the main limitation of this technique is the challenge of producing small 0927-7765/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.colsurfb.2009.10.030