title: Development and characterisation of sustained release solid dispersion oral tablets containing the poorly water soluble drug disulfiram.
abstract: Administration of drugs via the oral route is the most common and preferred route due to its ease of administration, cost-effectiveness and flexibility in design. However, if the drug being administered has limited aqueous solubility it can result in poor bioavailability. Furthermore, the low pH of the stomach as well as enzymatic activity can result in drugs delivered via the oral route being rapidly metabolised and degraded. Here we demonstrate the development and characterisation of sustained release solid dispersion oral tablets, containing the poorly water-soluble drug disulfiram (DSF). The tablets, which are manufactured from two different polymers (Kolliphor(®) P 188 and P 237) specifically designed for the manufacture of solid dispersions and two different polymers (Kollidon(®) SR and HPMC) specifically designed to provide sustained release, can enhance the solubility of DSF, sustain its release, while protecting it from degradation in simulated gastric fluid (SGF). The paper demonstrates that when using the hot melt method at 80°C the DSF loading capacity of the Kolliphor(®) P 188 and P 237 polymers is approximately 43 and 46% respectively, with the DSF completely in an amorphous state. The addition of 80% Kollidon(®) SR to the formulation completely protected the DSF in SGF for up to 70 min with 16% degradation after 120 min, while 75% degradation occurred after 120 min with the addition of 80% HPMC. The release rate of DSF can be manipulated by both the loading and type of sustained release polymer used, with HPMC providing for a much faster release rate compared to Kollidon(®) SR.
authors.affiliation: School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.
authors.forename: Mandip
authors.initials: M
authors.lastname: Shergill
authors.affiliation: School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.
authors.forename: Mina
authors.initials: M
authors.lastname: Patel
authors.affiliation: School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.
authors.forename: Siraj
authors.initials: S
authors.lastname: Khan
authors.affiliation: School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Bashir
authors.affiliation: School of Pharmacy, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. Electronic address: C.McConville.2@bham.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: McConville
mesh_terms: D000284:Administration, Oral; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004221:Disulfiram / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013607:Tablets; D014783:Viscosity
chemical_list: D003692:Delayed-Action Preparations; D011108:Polymers; D013607:Tablets; D004221:Disulfiram
keywords: Disulfiram; Hot melt; Solid dispersion; Solubility enhancement; Sustained release