Tags

Type your tag names separated by a space and hit enter

In vivo in vitro correlations for a poorly soluble drug, danazol, using the flow-through dissolution method with biorelevant dissolution media.
Eur J Pharm Sci. 2005 Mar; 24(4):305-13.EJ

Abstract

The purpose of the study was to design dissolution tests that were able to distinguish between the behaviour of danazol under fasted and fed conditions, by using biorelevant media. In vitro dissolution of 100mg danazol capsules was performed using the flow-through dissolution method. Flow rates were 8, 16 or 32 ml/min, corresponding to total volumes dissolution medium of 960, 1920 and 3840 ml, respectively. The media used contained bile salt and phospholipid levels relevant for either fasted or fed conditions in vivo. Crude and inexpensive bile components, Porcine Bile Extract and soybean phospholipids, were used as the bile source. The effect of adding different concentrations and molar ratios of monoglycerides and fatty acids to the fed state media was investigated. In vivo release profiles under fasted and fed conditions were obtained from a previous study by deconvolution [Sunesen, V.H., Vedelsdal, R., Kristensen, H.G., Christrup, L., Müllertz, A. 2005. Effect of liquid volume and food intake on the absolute bioavailability of danazol, a poorly soluble drug, Eur. J. Pharm. Sci. 24, 297-303]. In the fasted state, the physiologically most relevant correlation with in vivo results was achieved with a medium containing 6.3 mM bile salts and 1.25 mM phospholipids (8 ml/min). A medium containing 18.8 mM bile salts, 3.75 mM phospholipids, 4.0 mM monoglycerides and 30 mM fatty acids (8 ml/min) gave the closest correlation with fed state in vivo results. By using the flow-through dissolution method it was possible to obtain correlations with in vivo release of danazol under fasted and fed conditions. Both hydrodynamics and medium composition were important for the dissolution of danazol. In the fed state an IVIVC could only be obtained by including monoglycerides and fatty acids in the medium.

Authors+Show Affiliations

Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen O, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15734297

Citation

Sunesen, Vibeke Hougaard, et al. "In Vivo in Vitro Correlations for a Poorly Soluble Drug, Danazol, Using the Flow-through Dissolution Method With Biorelevant Dissolution Media." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 24, no. 4, 2005, pp. 305-13.
Sunesen VH, Pedersen BL, Kristensen HG, et al. In vivo in vitro correlations for a poorly soluble drug, danazol, using the flow-through dissolution method with biorelevant dissolution media. Eur J Pharm Sci. 2005;24(4):305-13.
Sunesen, V. H., Pedersen, B. L., Kristensen, H. G., & Müllertz, A. (2005). In vivo in vitro correlations for a poorly soluble drug, danazol, using the flow-through dissolution method with biorelevant dissolution media. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 24(4), 305-13.
Sunesen VH, et al. In Vivo in Vitro Correlations for a Poorly Soluble Drug, Danazol, Using the Flow-through Dissolution Method With Biorelevant Dissolution Media. Eur J Pharm Sci. 2005;24(4):305-13. PubMed PMID: 15734297.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo in vitro correlations for a poorly soluble drug, danazol, using the flow-through dissolution method with biorelevant dissolution media. AU - Sunesen,Vibeke Hougaard, AU - Pedersen,Betty Lomstein, AU - Kristensen,Henning Gjelstrup, AU - Müllertz,Anette, Y1 - 2005/01/06/ PY - 2003/07/25/received PY - 2004/09/28/revised PY - 2004/11/17/accepted PY - 2005/3/1/pubmed PY - 2005/7/29/medline PY - 2005/3/1/entrez SP - 305 EP - 13 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 24 IS - 4 N2 - The purpose of the study was to design dissolution tests that were able to distinguish between the behaviour of danazol under fasted and fed conditions, by using biorelevant media. In vitro dissolution of 100mg danazol capsules was performed using the flow-through dissolution method. Flow rates were 8, 16 or 32 ml/min, corresponding to total volumes dissolution medium of 960, 1920 and 3840 ml, respectively. The media used contained bile salt and phospholipid levels relevant for either fasted or fed conditions in vivo. Crude and inexpensive bile components, Porcine Bile Extract and soybean phospholipids, were used as the bile source. The effect of adding different concentrations and molar ratios of monoglycerides and fatty acids to the fed state media was investigated. In vivo release profiles under fasted and fed conditions were obtained from a previous study by deconvolution [Sunesen, V.H., Vedelsdal, R., Kristensen, H.G., Christrup, L., Müllertz, A. 2005. Effect of liquid volume and food intake on the absolute bioavailability of danazol, a poorly soluble drug, Eur. J. Pharm. Sci. 24, 297-303]. In the fasted state, the physiologically most relevant correlation with in vivo results was achieved with a medium containing 6.3 mM bile salts and 1.25 mM phospholipids (8 ml/min). A medium containing 18.8 mM bile salts, 3.75 mM phospholipids, 4.0 mM monoglycerides and 30 mM fatty acids (8 ml/min) gave the closest correlation with fed state in vivo results. By using the flow-through dissolution method it was possible to obtain correlations with in vivo release of danazol under fasted and fed conditions. Both hydrodynamics and medium composition were important for the dissolution of danazol. In the fed state an IVIVC could only be obtained by including monoglycerides and fatty acids in the medium. SN - 0928-0987 UR - https://www.unboundmedicine.com/medline/citation/15734297/In_vivo_in_vitro_correlations_for_a_poorly_soluble_drug_danazol_using_the_flow_through_dissolution_method_with_biorelevant_dissolution_media_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928-0987(04)00294-5 DB - PRIME DP - Unbound Medicine ER -