Sparingly soluble drugs

Recent Improvements in the Potentiometric Method Applied to Sparingly Soluble Drugs... 

Fig. 3.3 Solubility profiles of sparingly soluble drugs, based on data taken from Avdeef et al. [20]. The solutions consisted of robotically adjusted universal buffers, based on a mixture of Good buffers (see text), and contained 0.2 M KCl. The dashed lines were calculated by the Henderson-Hasselbalch equation and, as can be seen, did not accurately describe the solubility profiles. The solid curves were...

P Stout, N Khoury, J Mauger, S Howard. Evaluation of a tube method for determining diffusion coefficients for sparingly soluble drugs. J Pharm Sci 75 65, 1986. 

E. K. Anderberg, M. Bisrat, C. Nystrom. Physicochemical aspects of drug release. VII. The effect of surfactant concentration and drug particle size on solubility and dissolution rate of felodipine, a sparingly soluble drug. Int. I. Pharm. 1988, 47, 67-77. 

Bisrat M, Anderberg EK, Barnett MI, Nystrom C. Physicochemical aspects of drug release XV. Investigation of diffu-sional transport in dissolution of suspended, sparingly soluble drugs. Int J Pharm 1992 80 191—201. 

Anderberg, E.K., Bisrat, M., and Nystrom, C. (1988), Physicochemical Aspects of Drug Release. VII. The Effect of Surfactant Concentration and Drug Particle Size on Solubility and Dissolution Rate of Felodipine, a Sparingly Soluble Drug, Intemat. J. of Pharma., 47, 67-77. 

Avdeef, A. (2007) Solubility of sparingly-soluble drugs. In Special issue. Dressman, J., Reppas, C. (eds) The importance of drug solubility. Advanced Drug Delivery Reviews, 59, 568-590. 

Depot injections Typically a sparingly soluble drug as a solid or and implants dispersed in an oil. Easier to administer in... 

Simultaneous Determination of the Ionization Constant and the Solubility of Sparingly Soluble Drug Substances 225... 

Sjokvist E, Nystrom C, Alden M, Caram-Lelham N. Physicochemical aspects of drug release. XIY. The effects of some ionic and non-ionic surfactants on properties of a sparingly soluble drug in solid dispersions. Int J Pharm 1992 79 123-133. 

Muller, B.W. and Albers, E. (1991). Effect of hydrotropic substances on the complexation of sparingly soluble drugs with cyclodextrin derivatives and the in uence of cyclodextrin complexation on the pharmacokinetics. Pharm. Sci., 80, 599. 

Shell, J. W., and Louie-Helm, J. Gastric-retentive oral drug dosage forms for the con-trolled-release of sparingly soluble drugs and insoluble matter. U.S. Patent 5,972,389, 1999. 

Water-soluble polymers conjugated with lipids can form micelles in aqueous media, and they can be used for the solubilization and enhanced delivery of a variety of sparingly soluble drugs. The basic structures of these polymer-lipid conjugates are similar to amphiphilic block copolymers except for the fact that hydrophobic parts are composed of lipids instead of hydro-phobic polymers. For example, a hydrophilic PEG block is conjugated with phosphatidylethanolamine. ... 

This effect of particle size on dissolution rate of sparingly soluble drug substances has been demonstrated in many instances by the superior dissolution rates observed after size reduction. Examples of compounds studied in such work include methylprednisolone (Higuchi et al., 1963), l-isopropyl-7-methyl-4-phenylquinazolin-2(lH)-one (Kornblum and Hirschorn, 1970), griseofulvin (Ullah and Cadawader, 1971), monophenylbutazone (Habib and Attia, 1985), nitrofurantoin (Eyjolfsson, 1999), and piroxicam (Swanepoel et al., 2000). 

Cyclodextrin complexation (See Chapter 40) can also represent a way to improve the stability and the solubility of sensitive drugs such as thalidomide. Thalidomide is currently in clinical use for the treatment and prevention of graft-versus-host disease in leukemia patients after bone marrow transplant. However, this drug is sparingly soluble in aqueous solutions (50 Kig/mL) and is readily hydrolyzed. Complexation with hydroxypropyl (3-cyclodextrin increases the solubility to 1700 Kig/mL and extends the half-life of a dilute solution from 2.1 to 4.1 h. Other vulnerable and sparingly soluble drugs stabilized by means of cyclodextrin complexation are the non-steroidal antiinflammatory drugs diclofenac, piroxicam, and indomethacin and the anthra-cycline antibiotic daunorubicin. ... 

Chaurel N, Lloyd DK, Levorse D, Nicoll-Griffith DA. Automated pKa determination of soluble and sparingly soluble drugs by capillary zone electrophoresis. Pharm Sci 1995 1 59-62. 

Johansson D, Abrahamsson B. In vitro evaluation of two different dissolution enhancement principles for a sparingly soluble drug administered as extended-release (ER) tablet. Proc 24th Int Symp Controlled Release Bioact Mater, 1997 363-364. 

FIGURE 3.22 DSC traces of griseofulvin (a) quenched, (b) quenched after 9 months storage under ambient conditions, (c) quenched followed by size reduction, (d) quenched (slower solidification), and (e) raw material. (Reproduced from Mosharraf, M., The Effects of Solid State Properties on Solubility and In Vitro Dissolution Behaviour of Suspended Sparingly Soluble Drugs, Ph.D. thesis, University of Uppsala, 1999. With permission.)... 

Mosharraf, M., The Effects of Solid State Properties on Solubility and In Vitro Dissolution Behaviour of Suspended Sparingly Soluble Drugs, Ph.D. thesis, University of Uppsala, 1999. 

The dissolution rate, rather than the saturation solubility, is most often the primary determinant in the absorption process of a sparingly soluble drug. Experimental determinations of the dissolution rate are therefore of great importance. The main area for dissolution rate studies is evaluation of different solid forms of a drug (e.g., salts, solvates, polymorphs, amorphous, stereoisomers) or effects of particle size. The dissolution rate can either be determined for a constant surface area of the drug in a rotating disc apparatus or as a dispersed powder in a beaker with agitation. 

The presence of physiological surface-active agents in the stomach and small intestine will influence the solubility and the dissolution of sparingly soluble drugs by improved wetting of solid particle surface areas and by micellar solubilisation. This has been reviewed in more detail by Gibaldi and Feldman (1970) and Charman et al. (1997). 

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