Research paper Polyvinylalcohol substituted with triethyleneglycolmonoethylether as a new material for preparation of solid dispersions of hydrophobic drugs Isabella Orienti a, * , Federica Bigucci a , Barbara Luppi a , Teresa Cerchiara a , Guendalina Zuccari a , Paolo Giunchedi b , Vittorio Zecchi a a Department of Pharmaceutical Sciences, Bologna University, Bologna, Italy b Department of Pharmaceutical Sciences, Sassari University, Sassari, Italy Received 27 August 2001; accepted in revised form 13 March 2002 Abstract Among the different methods used to increase the aqueous drug solubility, the preparation of a solid dispersion with a soluble carrier represents an interesting formulative approach. We substituted polyvinylalcohol with triethyleneglycolmonoethylether and obtained a suitable material for the formulation of a solid dispersion of progesterone, by spray-drying. In particular, we evaluated the influence of the polyvinylalcohol substitution degree and the polymer–drug weight ratios in the preparative mixture on the progesterone dissolution rate in the aqueous environment. q 2002 Elsevier Science B.V. All rights reserved. Keywords: Substituted polyvinylalcohol; Diethoxyethylether; Progesterone; Drug–polymer affinity; Free drug availability 1. Introduction The solubility of a drug is an important factor in deter- mining the rate and extent of absorption and thus the appear- ance and intensity of the therapeutical effect. Poorly soluble drugs are characterized by a low tendency to dissolve in the aqueous fluids of the administration environment. After their oral administration, this results in poor bioavailability, whereas after parenteral administration, the therapeutic effect is delayed resulting in a weak therapeutic response. To overcome these problems many chemical and formula- tion approaches aim to improve the release rate of poorly soluble drugs. Chemical approaches are mainly based on the formation of soluble prodrugs or salts. Formulation approaches are mainly based on the use of polymorphous [1] or amorphous [2] forms of the drug, complexation, a decrease of particle size and drug dispersions in soluble solid carriers. Drug dispersions are now receiving increas- ing attention for their easy preparation, the possibility to use a wide range of carriers and their suitability for any drug. Polyethylene glycol, polyvinylpyrrolidone, polyvinylalco- hol (PVA), cellulose derivatives (HPMC, HPC, CMEC, HPMCP), polyacrylates and polymethacrylates have been extensively tested as carriers for solid dispersions with many drugs [3–9]. The physico-chemical characteristics of the polymer and the polymer–drug ratio influence drug release from the solid dispersions [10–13]. In the presence of a high polymer–drug ratio, the increased drug dissolution rate, based on the increased surface area of the dispersed drug that comes into contact with the dissolution medium after carrier dissolution, may be counterbalanced by an increased viscosity in the diffusion boundary layer adjacent to the dissolving surface due to the presence of the polymer in solution. The choice of the polymer and the polymer– drug ratio is thus very important in the preparation of solid drug dispersion suitable for a drug dissolution increase. This work describes the use of PVA substituted with triethylene- glycolmonoethylether (TEGME) as a carrier for the preparation of solid dispersions of progesterone chosen as a poorly soluble drug model. We substituted PVA with TEGME at different substitution degrees and evaluated the functional properties of these derivatives both in terms of their physico-chemical characteristics and their ability to provide solid dispersions of progesterone increasing its dissolution rate in an aqueous environment. To obtain substituted polymers also suitable for parenteral use, PVA 10,000 Mw was used in the present study providing, after substitution, polymers not exceeding 40,000, the molecular weight threshold for renal excretion [14]. European Journal of Pharmaceutics and Biopharmaceutics 54 (2002) 229–233 0939-6411/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. PII: S0939-6411(02)00055-3 www.elsevier.com/locate/ejphabio * Corresponding author. Department of Pharmaceutical Sciences, Bologna University, Via S. Donato 19/2, 40127 Bologna, Italy. Tel./fax: 139-51-253664. E-mail address: orienti@biocfarm.unibo.it (I. Orienti).