Danazol, solubility

Lomstein Pedersen B, Mullertz A, Brondstedt H, Gjelstrup Kristensen H (2000) A comparison of the solubility of danazol in human and simulated gastrointestinal fluids. Pharm. Res. 17 891-894. 

Table 17.2 illustrates the absolute oral bioavailability of several Danazol formulations nanoparticle dispersion, solubilized cyclodextrin oral formulation, and conventional suspension. Danazol represents a poorly water-soluble compound (H /mL) whose oral bioavailability is dissolution limited. 

Sunesen, V.H., et allp vivo-in vitro correlations for a poorly soluble drug, danazol, using the... 

Sunesen, V.H. Pedersen, B.L. Kristensen, H.G. Mullertz, A. 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), 305-313. 

Sunesen, V.H., Vedelsdal, R., Kristensen, H.G., Christrup, L. and Mullertz, A. (2005) Effect of liquid volume and food intake on the absolute bioavailability of danazol, a poorly soluble drug. European Journal of Pharmaceutical Sciences, 24, 297-303. 

Figure 5. The solubility of danazol as a function of the total surfactant concentration (R = 0.98) in the media listed in Table 4 (Sunesen et al., 2003).

Pedersen BL, Mullertz A, Brondsted H, and Kristensen HG. A Comparison of the Solubility of Danazol in Human and Simulated Gastrointestinal Fluids. Pharm Res 2000h 17 891-894. 

Sunesen VH, Pedersen BL, Kristensen HG, and Mullertz A. In Vivo in Vitro Correlations for a Poorly Soluble Drug, Danazol, Using the Flow-Through Dissolution Method With Biorelevant Dissolution Media. EurJPharm Sci 2005 24 305-313. 

Figure 14 Danazol is a drug with an aqueous solubility of 10 ttg/mL. Here danazol plasma levels are plotted as a function of time after administration of three forms of the drug including a nanoparticle dispersion and a hydroxypropyl-P-cyclodextrin complex, using a suspension with a mean particle size of 10 pm as a comparator. Source From Ref. 83.

Figure 14 demonstrates the advantage in the case of danazol of the use of nanoparticulate dispersions compared with conventional suspensions. The saturation solubility (25°C) of danazol in water has been found to range from 0.58 pg/mL to the lOpg/mL cited in reference 83. 

Jain AC, Adeyeye MC, Hydropho-bicity, phase solubility and dissolution of various substituted sulfobutylether-y -cyclodextrin (SBE) and danazol-SBE inclusion complexes, Int. J. Pharm. 2001 212 177-186. 

Liversidge and Cundy reported a dramatic increase in the oral bioavailabiUty of a nanoparticulate danazol composition relative to a micronized composition when administered to fasted beagle dogs. Danazol, sold under the ttadename Danocrine , is a synthetic steroid used to tfeat endometriosis. It has an aqueous solubility of approximately lOpg/mL and has the chemical sttucture shown in Fig. 3. 

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