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Free flowing solid dispersions of the anti-HIV drug UC 781 with Poloxamer 407 and a maximum amount of TPGS 1000: investigating the relationship between physicochemical characteristics and dissolution behaviour.
Eur J Pharm Sci. 2008 Sep 02; 35(1-2):104-13.EJ

Abstract

Solid dispersions and physical mixtures made up of the poorly water-soluble drug UC 781, a polymer and a surfactant were prepared to contribute to the understanding of the relationship between physicochemical characteristics and dissolution behaviour. In addition, to facilitate downstream processing while still favouring drug dissolution to a maximum extent, formulation conditions were investigated to obtain a free flowing powder which contains a maximum amount of surfactant. Poloxamer 407, a polyethylene-polypropylene glycol block copolymer, was selected as a suitable polymer based on UC 781 supersaturation results. d-Alpha-tocopheryl polyethyleneglycol succinate 1000 (TPGS 1000) was preferred as a surfactant since it increased UC 781 dissolution when formulated in a self-micro emulsifying drug delivery system (SMEDDS), as compared to TPGS 400, TPGS 4000 and TPGS 6000. Based on flow properties, a TPGS 1000/Poloxamer 407 ratio of 80/20 was used to prepare solid dispersions by spray drying. Pure drugs, physical mixtures and solid dispersions were characterized by differential scanning calorimetry and X-ray powder diffraction. Eutectic phase behaviour was obtained in which the relative distribution of the polyethylene glycol folding was dependent on UC 781 concentration. Drug release was markedly increased when formulated as a solid dispersion with Poloxamer 407 and TPGS 1000. Formulation of solid dispersions did however not further improve the drug dissolution rate compared to that of physical mixtures. Nonetheless, variability of dissolution results was considerably reduced upon solid dispersion formulation.

Authors+Show Affiliations

Laboratory of Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18644442

Citation

Goddeeris, Caroline, and Guy Van den Mooter. "Free Flowing Solid Dispersions of the anti-HIV Drug UC 781 With Poloxamer 407 and a Maximum Amount of TPGS 1000: Investigating the Relationship Between Physicochemical Characteristics and Dissolution Behaviour." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 35, no. 1-2, 2008, pp. 104-13.
Goddeeris C, Van den Mooter G. Free flowing solid dispersions of the anti-HIV drug UC 781 with Poloxamer 407 and a maximum amount of TPGS 1000: investigating the relationship between physicochemical characteristics and dissolution behaviour. Eur J Pharm Sci. 2008;35(1-2):104-13.
Goddeeris, C., & Van den Mooter, G. (2008). Free flowing solid dispersions of the anti-HIV drug UC 781 with Poloxamer 407 and a maximum amount of TPGS 1000: investigating the relationship between physicochemical characteristics and dissolution behaviour. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 35(1-2), 104-13. https://doi.org/10.1016/j.ejps.2008.06.010
Goddeeris C, Van den Mooter G. Free Flowing Solid Dispersions of the anti-HIV Drug UC 781 With Poloxamer 407 and a Maximum Amount of TPGS 1000: Investigating the Relationship Between Physicochemical Characteristics and Dissolution Behaviour. Eur J Pharm Sci. 2008 Sep 2;35(1-2):104-13. PubMed PMID: 18644442.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Free flowing solid dispersions of the anti-HIV drug UC 781 with Poloxamer 407 and a maximum amount of TPGS 1000: investigating the relationship between physicochemical characteristics and dissolution behaviour. AU - Goddeeris,Caroline, AU - Van den Mooter,Guy, Y1 - 2008/07/03/ PY - 2008/04/15/received PY - 2008/05/26/revised PY - 2008/06/18/accepted PY - 2008/7/23/pubmed PY - 2008/11/1/medline PY - 2008/7/23/entrez SP - 104 EP - 13 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 35 IS - 1-2 N2 - Solid dispersions and physical mixtures made up of the poorly water-soluble drug UC 781, a polymer and a surfactant were prepared to contribute to the understanding of the relationship between physicochemical characteristics and dissolution behaviour. In addition, to facilitate downstream processing while still favouring drug dissolution to a maximum extent, formulation conditions were investigated to obtain a free flowing powder which contains a maximum amount of surfactant. Poloxamer 407, a polyethylene-polypropylene glycol block copolymer, was selected as a suitable polymer based on UC 781 supersaturation results. d-Alpha-tocopheryl polyethyleneglycol succinate 1000 (TPGS 1000) was preferred as a surfactant since it increased UC 781 dissolution when formulated in a self-micro emulsifying drug delivery system (SMEDDS), as compared to TPGS 400, TPGS 4000 and TPGS 6000. Based on flow properties, a TPGS 1000/Poloxamer 407 ratio of 80/20 was used to prepare solid dispersions by spray drying. Pure drugs, physical mixtures and solid dispersions were characterized by differential scanning calorimetry and X-ray powder diffraction. Eutectic phase behaviour was obtained in which the relative distribution of the polyethylene glycol folding was dependent on UC 781 concentration. Drug release was markedly increased when formulated as a solid dispersion with Poloxamer 407 and TPGS 1000. Formulation of solid dispersions did however not further improve the drug dissolution rate compared to that of physical mixtures. Nonetheless, variability of dissolution results was considerably reduced upon solid dispersion formulation. SN - 0928-0987 UR - https://www.unboundmedicine.com/medline/citation/18644442/Free_flowing_solid_dispersions_of_the_anti_HIV_drug_UC_781_with_Poloxamer_407_and_a_maximum_amount_of_TPGS_1000:_investigating_the_relationship_between_physicochemical_characteristics_and_dissolution_behaviour_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928-0987(08)00299-6 DB - PRIME DP - Unbound Medicine ER -