Original Article Utility of plasticised polymer in solid dispersions for solubility enhancement of thermosensitive and poorly soluble API Viraj Vitthal Kulthe a, *, Pravin Digambar Chaudhari b , Subhashis Chakraborty c a Research Scholar, Department of Pharmaceutics, Institute of Pharmacy, National Institute of Medical Sciences University, Shobha Nagar, Jaipur 303121, Rajasthan, India b Principal and Professor in Pharmaceutics, Modern College of Pharmacy, Nigdi, Pune 411044, Maharashtra, India c Technical Head, Evonik Industries AG Pharma Polymers, Andheri (E), Mumbai 400072, Maharashtra, India article info Article history: Received 6 April 2013 Accepted 8 May 2013 Available online 25 May 2013 Keywords: Accelerated stability study Acetazolamide Hot melt extrusion Plasticiser Thermal degradation abstract Background/objective: Despite sophisticated technique as hot melt extrusion has established its place in formation of amorphous molecular dispersions, the advantage of which can’t be extrapolated to thermosensitive poorly soluble API, like Acetazolamide, because of inherent formulation problems such as degradation and/or browning following melting, residual crystallinity if processed at lower temperature than its melting point and pro- cessing problems such as poor extrudability. Thus the present study interestingly explores a stepwise approach to obtain solubility enhanced, thermodynamically stable amorphous molecular dispersions of thermosensitive drugs by hot melt extrusion technique. Methods: Solid dispersions of Acetazolamide with a polymethacrylate solubiliser in 1:1 and 1:2 weight ratios and with a solubiliser and a plasticiser in 1:2:0.15 and 1:2:0.30 weight ratios were prepared by hot melt extrusion and studied for drug content, thermal degra- dation, molecular interactions, solid state characterisation, solubility characteristics and subsequently accelerated stability study. Results: The formulation and the processing problems associated with solid dispersions of Acetazolamide with a solubiliser were overcome by coprocessing their optimised propor- tion with appropriate proportion of plasticiser, giving completely amorphous, molecular dispersions of Acetazolamide with markedly enhanced solubility characteristics. During stability study, the optimised proportion of solid dispersions reported only an insignificant change in solubility characteristics and amorphous nature of the drug. Conclusion: Thus, the study provided formulation strategies in a stepwise manner to enhance solubility characteristics of a poorly soluble API showing thermal degradation when processed by hot melt extrusion. Copyright ª 2013, JPR Solutions; Published by Reed Elsevier India Pvt. Ltd. All rights reserved. * Corresponding author. Tel.: þ91 9922114984; fax: þ91 2027661314. E-mail address: virajkulthe@rediffmail.com (V.V. Kulthe). Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/jopr journal of pharmacy research 6 (2013) 515 e521 0974-6943/$ e see front matter Copyright ª 2013, JPR Solutions; Published by Reed Elsevier India Pvt. Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jopr.2013.05.007