Soluble drugs, poorly

Mulye, N. 2002. Self-emulsifying compositions for drugs poorly soluble in water, US Patent 6436430-Bl. 

It is often assumed that drug solutions must be the most bioavailable form of the drug, but solutions of drugs poorly soluble at tissue pH will precipitate at the site of injection and subsequently release from the site might be slow. Precipitation may also occur if the drug is solubilized in a mixed solvent. In the presence of surfactant, as solubility is in most cases a linear function of surfactant... 

Besides the shortcomings noted above, some of the early sulfa drugs were poorly soluble in water. Since the drugs are excreted largely unchanged in the urine, crystals of the compounds sometimes formed in the kidneys and urine with attendant discomfort and tissue damage. Considerable attention was therefore devoted to preparation of agents with better solubility characteristics. ... 

Lipinski, C. A. (2000). Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Tox. Meth. 44 235-249. 

A large variety of drug delivery systems are described in the literature, such as liposomes (Torchilin, 2006), micro and nanoparticles (Kumar, 2000), polymeric micelles (Torchilin, 2006), nanocrystals (Muller et al., 2011), among others. Microparticles are usually classified as microcapsules or microspheres (Figure 8). Microspheres are matrix spherical microparticles where the drug may be located on the surface or dissolved into the matrix. Microcapsules are characterized as spherical particles more than Ipm containing a core substance (aqueous or lipid), normally lipid, and are used to deliver poor soluble molecules... 

It is poorly soluble in acetone, 2-butanone, ethyl acetate, acetonitrile, and DMF, and insoluble in alcohols, petroleum ether, and diethyl ether. The partition coefficients of a number of solutes between PCL and water have been measured and correlated with octanol-water partition coefficients (Fig. 9) (58,59). The linear correlation (Eq. 2) when combined with the water solubility of the solutes serves as a method of estimating the solubility of drugs in PCL from first principles. ... 

Lipinski CA. Drug-like properties and the causes of poor solubility and poor... 

Lipinski, C.A. (2000) Drug-like Properties of Poor Solubility and Poor Permeability. Journal of Pharmacological and Toxicological Methods, 44(1), 235-249. 

Where does Drug Poor Water Solubility Come From ... 

For drugs that are amines, the free base is frequently poorly soluble, and in this case the pK is often estimated by performing the titration in a solvent containing some organic solvent (e.g., ethanol). By doing this at different organic solvent concentrations (e.g., 5, 10, 15, 20%), extrapolation can be carried out to 0% solvent concentration to estimate the aqueous pK. 

Nanosuspensions for the Formulation of Poorly Soluble Drugs. Stuttgart Medpharm Scientific Publishers, 1998, pp 149-174. 

SH Klang, M Parnas, S Benita. Emulsions as drug carriers - possibilities, limitations and future perspectives. In RH Muller, S. Benita, BHL Bohm, eds. Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs. Stuttgart Medpharm Scientific Publishers, 1998, pp 31-78. 

RH Muller, K Peters. Nanosuspensions for the formulation of poorly soluble drugs I.Preparation by a size-reduction technique. Int J Pharm 160(2) 229-237, 1998. 

Another approach to improving the wettability of poorly soluble drugs is to treat the drug with a solution of a hydrophilic polymer. Lerk et al. [137] reported that both wettability of the powder and the rate of dissolution of hexobarbital from hard gelatin capsules could be greatly enhanced if the drug were treated with methylcellulose or hydroxyethylcellulose. In this process, called hydrophilization, a solution of the... 

Concentrated Oral Solutions. Presentation of a drug may be made in the form of a concentrated solution that allows the entire dose to be held within a volume of less than 5 mL (e.g., Intensol Concentrated Oral Solutions, Roxanne). This opens up another means of providing medication to the aged, infants, or any other patients experiencing difficulties swallowing. Such preparations can be mixed with food or drink. Taste and poor solubility are problems that may set limits on the number of successful formulations that can be prepared in this way. Also, small errors in the measurement of such preparations represent large errors in dosing. 

An interesting paper that attempted to relate dissolution of a poorly soluble acidic drug (naproxen) to simulated gastrointestinal flow in the presence of buffers was published by Chakrabarti and Southard [17]. In addition to showing that buffer type (citrate, phosphate, or acetate) had a significant impact on naproxen dissolution, these authors unexpectedly found that elevating a solid tablet into the flow channel of the flow-between-two-plates apparatus resulted in a substantial... 

VI. DISSOLUTION OF POORLY SOLUBLE DRUGS IN EMULSION SYSTEMS... 

As with micelle-facilitated dissolution, emulsion-facilitated dissolution has gained renewed interest due to its application to water-insoluble drug delivery and enhanced absorption. Over the years, emulsion systems have been developed and used to either model the in vivo dissolution process or mimic the intestinal surfactant system to enhance drug delivery of poorly soluble compounds [54-66], Emulsions have also been used as vehicles for drug delivery, e.g., to protect... 

S Chakrabarti, MZ Southard. Control of poorly soluble drug dissolution in conditions simulating the gastrointestinal tract flow. 1. Effect of tablet geometry in buffered medium. J Pharm Sci 85 313-319, 1996. 

---