Colloids and Surfaces B: Biointerfaces 72 (2009) 141–147 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb Solubilization of poorly water-soluble drug carbamezapine in Pluronic ® micelles: Effect of molecular characteristics, temperature and added salt on the solubilizing capacity Yogesh Kadam a,∗ , Usha Yerramilli a , Anita Bahadur b a Department of Chemistry, V.N. South Gujarat University, Surat 395 007, Gujarat, India b Department of Zoology, P.T. Sarvajanik College of Science, Surat 395 001, India article info Article history: Received 14 February 2009 Received in revised form 24 March 2009 Accepted 26 March 2009 Available online 5 April 2009 Keywords: Solubilization Micelle Block copolymer Micelle–water partition coefficient (P) abstract The solubilization of a poorly water-soluble antiepileptic drug, carbamazepine (CBZ), in a series of micelle- forming PEO–PPO–PEO block copolymers with combinations of blocks having different molecular weight was studied. The drug solubility and micelle–water partition coefficient (P) were determined using UV–vis spectroscopy. Dynamic light scattering on copolymer solutions was used to measure size and polydis- persity of nanoaggregates. Solubilization of carbamezapine increased with the rise in temperature and concentration of block copolymers, but no significant increase was observed with added salt (NaCl). The solubilization is also discussed from a thermodynamics viewpoint, by considering the standard free energy of solubilization (G ◦ ). © 2009 Elsevier B.V. All rights reserved. 1. Introduction Several drugs of good clinical value have low water solubility, making the delivery of these drugs by conventional means dif- ficult. Various techniques such as using suitable solvents [1–4], hydrophobically modified polysaccharides [5–7], dendrimers [8], hydrotropes [9], nanostructured fluids such as vesicles [10] and sur- factant micelles [11–23] have been used in the literature to enhance the aqueous solubility of such sparingly water-soluble drugs. Block copolymers can be used to solubilize these sparingly soluble drugs and serve as biocompatible drug delivery systems. Block copolymers are made of two often incompatible blocks that show micro-domain formation in solid state and aggregation in selective solvents [11–13]. Amphiphilic block copolymers assem- ble into nanoscopic supramolecular core–shell structures, termed polymeric micelles, which are under extensive study for drug sol- ubilization, delivery systems [14–23]. These polymer micelles are nanosized particles that can solubilize hydrophobic drugs and alter their kinetics in vitro and in vivo. Poly(ethylene oxide) n –poly(propylene oxide) m –poly(ethylene oxide) n (PEO–PPO–PEO), are amphiphilic substances often called Pluronic ® (BASF) or Poloxamers, and have numerous industrial applications as detergents, dispersants, stabilizers, foaming agents, ∗ Corresponding author. Tel.: +91 999 8481106; fax: +91 261 2256012. E-mail address: yogeshkadam2010@yahoo.com (Y. Kadam). emulsifiers, etc. Pluronics ® behave as non-ionic surfactants and form core–shell micelle [a hydrophobic core of (PPO) and a hydrophilic shell of heavily hydrated (PEO)], above a certain tem- perature, called the critical micellization temperature, CMT, which depends on the concentration/molecular characteristics of the copolymer. These micelles can be spherical or rod-like (even aggregates of different morphologies including vesicles) in dilute solution but organize to exhibit rich phase behavior in concen- trated solutions often forming viscoelastic gels under experimental conditions. The micelle formation and phase behavior of Pluronic ® surfactants have been investigated by several workers and is exten- sively reviewed [24–28]. There have been a few studies on the solubilization of hydropho- bic drugs having different pharmacological activity in Pluronic ® micelles. Increased solubility and longer half-life of naproxen and rofecoxib was shown by Suh et al. [29,30] and Ahuja et al. [31]. Barreiro-Iglesias et al. [32] showed that solubility of camptothecin, an anticancer drug was 3–4-fold higher with modified PAA blocks in comparison to single Pluronic ® block copolymer F127 and L92, whereas Sugin et al. [33] showed improved oral absorption in vitro with F127, F68, and P85. Solubility of tropicamide a mydri- atic/cycloplegic drug was studied [34] with a series of Pluronic ® with different molecular characteristics and found that ocular sol- ubility increased linearly with increasing surfactant concentration and enhanced solubility for higher EO content. Neuroleptic drug haloperidol showed a 5-fold increase in solubility in Pluronic ® P85 [35]. The solubility of estriol an HRT drug increased with 0927-7765/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.colsurfb.2009.03.027