Solubilization drugs water soluble compounds

For formulating poor water-soluble compounds, use of cosolvent(s) is one of the simplest and common approach. The approach is also widely used in the early development phase, as limited information is available for the molecule. The approach also allows overcoming dissolution rate limited drug absorption. In addition, solubilized formulations are greatly popular with pediatric, geriatric, and patients with swallowing difculties. 

Identification of pharmaceutically acceptable vehicles that afford sufficient solubilization while maximizing physiological compatibility for preclinical pharmacokinetic evaluation is critical. The most frequently used solubilization techniques include pH manipulation for ionizable compounds use of cosolvents such as PEG 400, ethanol, DMSO, and propylene glycol micellar solubilization with surfactants such as Tween 80 or SLS complexation with cylodextrins [40]. By using the solubilization techniques, the enhancement in solubility of poor water-soluble compounds can be significant compared to aqueous solubility and can facilitate the absorption of drug molecules in the gastrointestinal tract when delivered in solution form. 

Another important factor that may inLuence solubility, dissolution rate, and therefore absorption of water-insoluble compounds is the contents ofthe Gl Luids. The Gl Luids contain various materials, such as bile salts, enzymes, and mucin. Bile salts are surface active and as such could potentially enhance the rate or extent of absorption of water-insoluble drugs. Thus, the increased absorption of a water-insoluble compound, griseofulvin (GF), after a fatty meal may be facilitated by bile salt secretion into the gut resulting in solubilization [1,2],... 

The major benefit of the solubilization principle is the increased water solubility of water-insoluble drugs such as phenolic compounds, iodine, steroids, and vitamins. The solubilization of water-insoluble materials in micelles may have some effects on drug activity and absorption. In addition, drugs in the micelles may prefer to stay... 

On the other hand, highly lipophilic compounds, such as hormones, can be solubilized via the prodrug approach. For example, the rate of transdermal absorption of the highly lipophilic drug, testosterone, was enhanced over 50-fold by forming water-soluble, yet lipophilic, prodrug ester.f The prodrug testoster-onyl-4-dimethylaminobutyrate was found to penetrate human skin tissue, in vitro, 54 times faster than... 

Cyclodextrins have been used for enhancing the solubility of poorly water-soluble small molecules (Shimpi et ah, 2005). The mechanism of solubilization is formation of reversible complexes between the hydrophobic moiety of the drug molecule and the hydrophilic cyclodextrin that is highly water soluble. A similar observation has been made with some proteins and peptides (Brewster et ah, 1991 Johnson et ah, 1994 Flores et ah, 2001). Sulfated cyclodextrins and 2-hydroxypropyl-beta-cyclodextrins are approved excipients for parenteral administration, however, use of these compounds should take into consideration the cost involved. 

During the discovery phase, when availability of compound is at a premium, the formulation of a simple injectable product for use in animal studies can be problematical. If a drug candidate required for formulation as a parenteral product is non-ionizable, lipophihc or does not form a water-soluble salt with acceptable properties, solubilization by use of cosolvents should be considered as the next option. In cases... 

---