Research paper Comparison of impact of the different hydrophilic carriers on the properties of piperazine-containing drug Mahrous Osman Ahmed * Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt Received 28 August 2000; accepted in revised form 11 January 2001 Abstract The objective of this study was to determine the impact of a series of nonionic surfactants on the solubility of piperazine-containing drug (meclizine, MZ) in comparison to that of natural cyclodextrins (a-CD and b-CD) and dimethyl-b-cyclodextrin (DM-b-CD). The solubility of the drug was studied in either CDs solutions or nonionic surfactant solutions. Three classes of nonionic surfactants were used namely; polyoxyethylene (POE) sorbitan fatty acid esters (polysorbates), POE fatty acid esters (Myrjs) and polyethylene oxide (PEO) fatty alcohol ethers (Brijs and Eumulgins). The solubility of MZ was increased linearly with the increasing surfactant concentration, indicating that micellar solubilization follows the partition model. It was found that the longer the hydrocarbon chain in a homologous series, the more ef®cient is the solubilizing power of surfactant. For example, polysorbate 80 (Tween-80) is a more ef®cient solubilizer than polysorbate 20 (Tween-20), indicating that the drug was incorporated in the core of micelle more than the capsular region of the micelle. On the other hand, in case of POE fatty acid esters, the solubilizing power increased with decreasing polyoxyethylene chain as Myrj 53 was more ef®cient than Myrj 59. In class of PEO fatty alcohol ethers, the shorter the hydrophilic chain and longer lipophilic chain, the more ef®cient was the solubilizing capacity. Thus, Brij 58 was more ef®cient solubilizer than Brij 35 and Eumulgin C1000 was more active than Eumulgin C1500. Comparatively, Eumulgin C1000 had the highest solubilizing power for MZ among the studied PEO fatty alcohol ethers and other groups of surfactants. The solubility action of surfactants toward MZ was increased by raising the temperature of the surfactant solutions from 30 to 458C. Hydrophilic macromolecules (PEG 1000 and PEG 6000) or cosolvents (glycerol and propylene glycol) have a very slight effect on the solubility of MZ and con®rm the predominance of hydrophobic interaction between the drug and nonionic surfactants. A L -type phase solubility diagrams were obtained for the drug with a-, b- and DM-b-CDs showing that the solubility of MZ was enhanced through inclusion complexation. Comparatively, DM-b-CD had the highest solubilizing ef®ciency for the drug among the investigated CDs, which could be attributed to its larger hydrophobic cavity size. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Meclizine; Solubility; Nonionic surfactant; Micellar solubilization; Cyclodextrin; Complexation 1. Introduction Transformation of water-insoluble drugs into solution is one of the main problems encountered in formulating such drugs in liquid dosage forms. Although several reports [1,2] have dealt with the solubilization of such drugs in nonionic surfactant solutions, more attention should be paid toward this phenomenon. Nonionic, rather than ionic, surfactant solutions have been employed in this aspect because of their lower toxicity, lower critical micellar concentration and their compatibility with body ¯uids [3]. Their micelles show a gradient of increased polarity from the core (the hydrocarbon chain) to the capsule (the polyoxyethylene chain)±water surface. The extended interfacial region between the core and aqueous solution, i.e. the polar mantle or capsule, is greatly hydrated. The anisotropic distribution of water molecules within the polar mantle favors the inclu- sion (solubilization) of a wide variety of molecules inside the micellar core [4]. Natural cyclodextrins (CDs), a-, b- and g-CD, have been extensively employed to improve solubility dissolution, stability and bioavailability of various poorly water-soluble drugs [5,6]. The chemically modi®ed cyclodextrins, such as dimethyl b-cyclodextrin (DM-b-CD) and trimethyl b- cyclodextrin (TM-b-CD), have received a considerable attention in pharmaceutical technology because of their advantageous physicochemical properties than the parent cyclodextrins [6], as they are much more soluble in both water and organic solvents. Both naturally occurring cyclo- dextrins and the chemically modi®ed ones are subject of European Journal of Pharmaceutics and Biopharmaceutics 51 (2001) 221±226 0939-6411/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S0939-6411(01)00128-X www.elsevier.com/locate/ejphabio * Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. Tel.: 120-88-501016; fax: 120-88- 332776. E-mail address: momahrous@yahoo.com (M.O. Ahmed).