Drug solubility effect

Hileman GA, Upadrashta SM, Neau SH. Drug solubility effects on predicting optimum conditions for extrusion and spheronization of pellets. Pharm Dev Tech 1997 2(l) 43-52. 

It is not only the solid state of a drug that suffers from ambiguities, but also the aqueous state. The state relevant for the intrinsic solubility is the state of the saturated solution of the neutral species. Since most aqueous drug solubilities are small, direct interactions of the drug molecules are usually rare. Hence, this state is usually very similar to the state of the drug at infinite dilution in water. Most computational methods disregard saturation effects. Usually this is a good approximation, but one should keep in mind that this approximation may result in some moderate, but systematic errors at the upper end of the solubility scale. 

Fig. 6 Solubility effects on drug stability curve A, drug formulated as lOmg/mL solution (q/2 = 1 year) curve B, drug formulated as a suspension with a saturated solubility of 1 mg/mL (ti/2 = 7.3 years). 

The role of lipids on absorption has been extensively reviewed by Porter and Charman [29, 30]. The influences are diverse and include effects on luminal drug solubility, altering the metabolic and barrier function of the intestinal wall, stimulating lymphatic transport and a reduction in gastric transit, thereby increasing the time available for dissolution. 

The effect of drug solubility on the release from PDADMAC is shown in Figure 5. The slightly soluble diclofenac (2.5 wt%) was released over a... 

Figure 5 Effect of drug solubility on drug release from drug-PDADMAC complex tablets at pH 7.0 (0.2 M NaCl). 

Figure 13 Effect of drug solubility on water required for 80% and 85% yields of pellets containing MCC. Source From Ref. 39.

Richardson, P. J., D. F. McCafferty, and A. D. V foolfson. 1992. Determination of three-component partial solubility parameters for temazepam and the effects of change in partial molal volume on the thermodynamics of drug solubility J. Pharm. 78 189-198. 

Serajuddin, A.T.M. et al. (1986) VWter migration from soft gelatin capsule shell to II material and its effect on drug solubility.J. Pharm. Sci., 75 62-64. 

Watari, N., Flanano, M., and Kaneniwa, N. (1980) Dissolution of slightly soluble drugs. VI. Effect of particle size of sulfadimethoxine on the oral bioavailabilifjtiem. Pharm. Bull., 28 2221-2225. 

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