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Development and characterisation of sustained release solid dispersion oral tablets containing the poorly water soluble drug disulfiram.
Int J Pharm. 2016 Jan 30; 497(1-2):3-11.IJ

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+Show Affiliations

School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfrana Street, Wolverhampton WV1 1LY, UK.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26608620

Citation

Shergill, Mandip, et al. "Development and Characterisation of Sustained Release Solid Dispersion Oral Tablets Containing the Poorly Water Soluble Drug Disulfiram." International Journal of Pharmaceutics, vol. 497, no. 1-2, 2016, pp. 3-11.
Shergill M, Patel M, Khan S, et al. Development and characterisation of sustained release solid dispersion oral tablets containing the poorly water soluble drug disulfiram. Int J Pharm. 2016;497(1-2):3-11.
Shergill, M., Patel, M., Khan, S., Bashir, A., & McConville, C. (2016). Development and characterisation of sustained release solid dispersion oral tablets containing the poorly water soluble drug disulfiram. International Journal of Pharmaceutics, 497(1-2), 3-11. https://doi.org/10.1016/j.ijpharm.2015.11.029
Shergill M, et al. Development and Characterisation of Sustained Release Solid Dispersion Oral Tablets Containing the Poorly Water Soluble Drug Disulfiram. Int J Pharm. 2016 Jan 30;497(1-2):3-11. PubMed PMID: 26608620.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development and characterisation of sustained release solid dispersion oral tablets containing the poorly water soluble drug disulfiram. AU - Shergill,Mandip, AU - Patel,Mina, AU - Khan,Siraj, AU - Bashir,Ayesha, AU - McConville,Christopher, Y1 - 2015/11/28/ PY - 2015/09/29/received PY - 2015/11/12/revised PY - 2015/11/14/accepted PY - 2015/11/27/entrez PY - 2015/11/27/pubmed PY - 2016/10/16/medline KW - Disulfiram KW - Hot melt KW - Solid dispersion KW - Solubility enhancement KW - Sustained release SP - 3 EP - 11 JF - International journal of pharmaceutics JO - Int J Pharm VL - 497 IS - 1-2 N2 - 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. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/26608620/Development_and_characterisation_of_sustained_release_solid_dispersion_oral_tablets_containing_the_poorly_water_soluble_drug_disulfiram_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(15)30374-4 DB - PRIME DP - Unbound Medicine ER -