title: Preparation and characterisation of Kolliphor® P 188 and P 237 solid dispersion oral tablets containing the poorly water soluble drug disulfiram.
abstract: The oral route of administration is the most common and preferred route of drug delivery due to its ease of administration, cost-effectiveness and flexibility in design. However, limited aqueous solubility of the active pharmaceutical ingredient can result in poor bioavailability, which is a major issue for the pharmaceutical industry. Increasing numbers of new drugs are falling into class II of the Biopharmaceutical Classification System (BCS), where they have a low solubility and high tissue permeability, meaning that bioavailability is solubility dependent. Here we demonstrate the development and characterisation of solid dispersion oral tablets, containing the poorly water-soluble drug disulfiram, prepared using both the hot melt and solvent evaporation methods and manufactured from two different polymers, Kolliphor(®) P 188 and P 237, specifically designed for the manufacture of solid dispersions. This paper demonstrates that the disulfiram solid dispersions tablets have an enhanced release rate of disulfiram compared to the control tablets. The Kolliphor(®) P 188 polymer control tablets released approximately 48.8% of their disulfiram content over 8h, with the solvent evaporated tablets releasing approximately 65.8%, while the 60 and 80 °C hot melt tablets released approximately 73.2 and 100% of their disulfiram content respectively. A similar trend was seen with Kolliphor(®) P 237 as the control tablets released approximately 50.5% of their disulfiram content over 8h, while the solvent evaporated tablets released approximately 79.5% and the 60 and 80 °C hot melt tablets released 100.2 and 100.3% respectively. Depending on what method and polymer is used to manufacture the solid dispersions the disulfiram is either maintained completely or partially in its amorphous state and it is this which enhances its solubility and release rate from the tablets. The disulfiram in the Kolliphor(®) P 188 solvent evaporated and 60 °C hot melt tablets retained 50.5 and 44.1% of its crystallinity, while the disulfiram in the 80 °C hot melt tablets was completely amorphous. Whereas the disulfiram in the Kolliphor(®) P 237 solvent evaporated tablets retained 45.2% crystallinity, while the disulfiram in both of the hot melt tablets was completely in its amorphous form.
authors.affiliation: Department of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.
authors.forename: Nisrina
authors.initials: N
authors.lastname: Ramadhani
authors.affiliation: Department of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.
authors.forename: Mehwish
authors.initials: M
authors.lastname: Shabir
authors.affiliation: Department of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK. Electronic address: C.Mcconville@wlv.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: McConville
mesh_terms: D002152:Calorimetry, Differential Scanning; D004221:Disulfiram / Q000008:administration & dosage* / Q000737:chemistry*; D065546:Drug Liberation; D020442:Poloxamer / Q000737:chemistry*; D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D014961:X-Ray Diffraction
chemical_list: D013607:Tablets; D020442:Poloxamer; D004221:Disulfiram
keywords: Disulfiram; Hot melt; Solid dispersion; Solubility enhancement; Solvent evaporation