Physicochemical Characterisation, Drug Polymer Dissolution and in Vitro Evaluation of Phenacetin and Phenylbutazone Solid Dispersions with Polyethylene Glycol 8000 SHERAZ KHAN, 1 HANNAH BATCHELOR, 2 PETER HANSON, 1 YVONNE PERRIE, 1 AFZAL R. MOHAMMED 1 1 Aston Pharmacy School, Aston University, Birmingham B4 7ET, UK 2 Heart of England NHS Foundation Trust, Birmingham B9 5SS, UK Received 11 March 2011; revised 12 April 2011; accepted 20 April 2011 Published online 10 May 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jps.22613 ABSTRACT: Poor water solubility leads to low dissolution rate and consequently, it can limit bioavailability. Solid dispersions, where the drug is dispersed into an inert, hydrophilic polymer matrix can enhance drug dissolution. Solid dispersions were prepared using phenacetin and phenylbutazone as model drugs with polyethylene glycol (PEG) 8000 (carrier), by melt fusion method. Phenacetin and phenylbutazone displayed an increase in the dissolution rate when formulated as solid dispersions as compared with their physical mixture and drug alone coun- terparts. Characterisation of the solid dispersions was performed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and scanning electron mi- croscopy (SEM). DSC studies revealed that drugs were present in the amorphous form within the solid dispersions. FTIR spectra for the solid dispersions of drugs suggested that there was a lack of interaction between PEG 8000 and the drug. However, the physical mixture of phenacetin with PEG 8000 indicated the formation of hydrogen bond between phenacetin and the carrier. Permeability of phenacetin and phenylbutazone was higher for solid dispersions as compared with that of drug alone across Caco-2 cell monolayers. Permeability studies have shown that both phenacetin and phenylbutazone, and their solid dispersions can be categorised as well-absorbed compounds. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4281–4294, 2011 Keywords: solid dispersions; PEG 8000; Phenacetin; Phenylbutazone; FTIR; DSC; Dissolu- tion studies; Permeability; amorphous form INTRODUCTION Poor solubility of drugs in water and gastrointestinal fluids leads to low dissolution rates and consequently, it can limit bioavailability. Bioavailability of a drug is dependent on its solubility and permeability. 1 Tech- niques that have commonly been used to improve dissolution and bioavailability of poorly water-soluble drugs include salt formation, 2 micronisation, 3 the use of surfactants, 4 particulate delivery systems 5 and the formulation of solid dispersions. 6 Solid dispersions are defined as the dispersions of one or more active pharmaceutical ingredients in an inert hydrophilic Correspondence to: Afzal R. Mohammed (Telephone: +44-121- 2044183; Fax: +44-121-2044000; E-mail: a.u.r.mohammed@aston .ac.uk) Journal of Pharmaceutical Sciences, Vol. 100, 4281–4294 (2011) © 2011 Wiley-Liss, Inc. and the American Pharmacists Association carrier in solid state. It is a widely used technique to enhance drug dissolution and in turn, it promotes bioavailability of insoluble drugs. Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving dissolution and bioavailability of a range of hydrophobic drugs. 7 The enhanced drug dissolution can be ascribed to multiple factors, including conversion of crystalline drug into amorphous form, reduction in particle size and an im- proved wettability due to inert hydrophilic carrier. 8 The fabrication of solid dispersions is associated with the complexity of the release mechanism and the multitude of factors that can affect it, includ- ing the properties of drug, 9 particle size, 10 proper- ties of the polymer forming the matrix, 11 molecular weight, 12 physical state 13 and possible drug–polymer interaction. 14 Theories proposed for the drug release mechanisms from solid dispersions are dependent on the dissolution of both drug and polymer. Two widely JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 100, NO. 10, OCTOBER 2011 4281