Drugs poorly water-soluble

Etoposide (XV) is a semisynthetic gylcoside derivative of podophyllotoxin, which is one of the most extensively used anticancer drugs in the treatment of various types of tumors [64,65]. The anticancer activity of this drug is mainly due to its ability to inhibit an ubiquitous and essential enzyme human DNA topo II [66,67]. Despite its extensive use in the treatment of cancers, it has several limitations, such as poor water solubility, drug resistance, metabolic inactivation, myelosuppression, and toxicity [68]. In order to overcome these... 

Pouton, C. Formulation of poorly water-soluble drugs for oral administration Physicochemical and physiological issues and the lipid formulation classification system. Eur. J. Pharm. Sci. 2006, 29, 278-287. 

These mixing motions will tend to improve drug absorption for two reasons. Any factor that increases rate of dissolution will increase the rate (and possibly the extent) of absorption, especially for poorly water-soluble drugs (BCS Classes II and IV). Since rate of dissolution depends on agitation intensity, mixing movements will tend to increase dissolution rate and thereby influence absorption. As rate of absorption depends directly on membrane surface area, and since mixing increases the contact area between drug and... 

Dressman, J. B. Reppas, C., In vitro-in vivo correlations for lipophilic, poorly water-soluble drugs, Eur. J. Pharm. Sci. 11 (Suppl. 2), S73-S80 (2000). 

SS Kornblum, JO Hirschorn. Dissolution of poorly water-soluble drugs I. Some physical parameters related to method of micronization and tablet manufacture of a quinazolinone compound. J Pharm Sci 59 606-609, 1970. 

S. Yokohama. Common solubilizers to estimate the Caco-2 transport of poorly water-soluble drugs., Int. J. Pharm. 2002, 246, 85... 

Orally administered dosage forms are absorbed into the systemic circulation following dissolution in the GI tract. Because substances must be in solution for the absorption from the GI lumen, the absorption rate of poorly water-soluble drugs is limited by their rate of dissolution. The dissolution rate is affected by the unique physicochemical properties of the drug and by physiological factors the pH, composition, and hydrodynamics of the GI medium. 

Reduction of particle size increases the total specific surface area exposed to the solvent, allowing a greater number of particles to dissolve more rapidly. Furthermore, smaller particles have a small diffusion boundary layer, allowing faster transport of dissolved material from the particle surface [58]. These effects become extremely important when dealing with poorly water-soluble drugs, where dissolution is the rate-limiting step in absorption. There are numerous examples where reduction of particle size in such drugs leads to a faster dissolution rate [59-61], In some cases, these in vitro results have been shown to correlate with improved absorption in vivo [62-64]. 

Araya H, Tomita M, Hayashi M (2006) The novel formulation design of self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion III The permeation mechanism of a poorly water soluble drug entrapped O/W microemulsion in rat isolated intestinal membrane by the Ussing chamber method. Drug Metab Pharmacokinet 21 45-53. 

Watanabe E, Takahashi M, Hayashi M (2004) A possibility to predict the absorbability of poorly water-soluble drugs in humans based on rat intestinal permeability assessed by an in vitro chamber method. Eur J Pharm Biopharm 58 659-665. 

Kataoka M, Masaoka Y, Yamazaki Y, Sakane T, Sezaki H, Yamashita S (2003) In vitro system to evaluate oral absorption of poorly water-soluble drugs Simultaneous analysis on dissolution and permeation of drugs. Pharm Res 20 1674-1680... 

Serajuddin, A.T., Solid dispersion of poorly water soluble drugs early promises, subsequent problems, and recent breakthroughs, J. Pharm. Sci., 88,1058,1999. 

Serajuddin, A.T.M., Sheen, P.C., Mufson, D., Bernstein, D.F., and Augustine, M.A., Preformulation study of a poorly water soluble drug, alpha-pentyl-3-(2-quinolinyl-methoxy) benzenemethanol selection of the base for dosage form design, /. Pharm. Sci., 75, 492, 1986. 

Hasegawa A, Kawamura R, Nakagawa H, Sugimoto K. Physical properties of solid dispersions of poorly water-soluble drugs with enteric coating agents. Chem Pharm Bull 1985 33 3429-3435. 

Portero A, Remunanlopez C, Vilajato JL. Effects of chitosan and chitosan glutamate enhancing the dissolution properties of the poorly water soluble drug nifedipine. Int J Pharm 1998 175 75-84. 

Sertsou G, Butler J, Hempenstall J, Rades T. Solvent change co-precipitation with hydro-xypropylmethylcellulose phthalate to improve dissolution characteristics of a poorly water-soluble drug. J Pharm Pharmacol 2002 54 1041-1047. 

The lipidic vehicles and nanosuspensions described above are also used for increasing the loading of poorly water-soluble drugs, particularly in volume-constrained injections. 

Two-point specificationsFor slowly dissolving or poorly water soluble drugs (BCS Class II), a two-point dissolution speciLcation, one at 15 min to include a dissolution range (a dissolution window) and the other at a later point (30, 45, or 60 min) to ensure 85% dissolution, is recommended to characterize the quality of the product. 

Takano, R. et al., Oral absorption of poorly water-soluble drugs computer simulation of fraction absorbed in humans from a miniscale dissolution fgb rm. Res., 23, 1144, 2006. 

Dressman, J. B. and Reppas,l6yitro in vivocorrelations for lipophilic poorly water-soluble drugs,... 

Emulsions are either oil phase dispersed in water phase, an oil-in-water (o/w) emulsion, or water phase dispersed in oil phase, a water-in-oil (w/o) emulsion. If a poorly water-soluble drug substance is soluble in oil, it can be solubilized in an emulsion where it partitions into the oil phase. The total solubility in an emulsions, is the summation of concentrations in the aqueous and oil phases (Strickley, 2004). The total solubility of the emulsion system is the sum of the drug concentration in the aqueous phaseSv, and the concentration in the oil phase, which can be approximated by the product of the drug s solubility in the pure oi i, multiplied by the fraction of the oil in the emulsion ... 

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