Oral solution drug delivery solubility

Water-soluble polymers can also be used as aqueous solutions for drug delivery. Although the polymer is already dissolved, its increase in viscosity of the drug solution causes the drug to be retained somewhat longer in the desired application. This technique is common with ocular, nasal, and oral applications of drug solutions. 

Amphiphilic poly(ethylene glycol)-alkyl dextran ethers are emerging as vehicles in the oral delivery of poorly water soluble drugs [251,268,269]. They form polymer micelles of low critical association concentrations (CAC) and small micelle sizes in aqueous solution. Particulate delivery systems lead to an enhancement of the absorption efficiency and bioavailability of highly hpophihc drugs orally applied, and provide the drug with some level of pro-... 

Surfactants are employed in nanoparticle suspensions. Chen et al. (2002) evaluated the pre paration of amorphous nanoparticle suspensions containing cyclosporine A using the evaporative precipitation into aqueous solution (ERAS) system. The effect of particle size was studied varying the drug surfactant ratios, type of surfactants, temperature, drug load, and solvent. Acceptable particle sizes suitable for both oral and parenteral administration were also studied. Additional articles in the nanoparticle delivery of poorly water-soluble drugs include Kipp (2004), Perkins et al. (2000), Young et al. (2000), and Tyner et al. (2004). 

In this chapter we will provide a brief overview of the early approaches to bioavailability enhancement by use of simple lipid-based delivery systems (lipid solutions, emulsions etc), and then describe recent progress in the application of self-emulsifying- and microemulsion-based formulations. The effects of lipids on the oral bioavailability of co-administered poorly water-soluble drugs may also be classified from a mechanistic (and to a degree, historical) perspective as physicochemically mediated effects (solubility, dissolution, surface area) and biochemically mediated effects (metabolism, transport related events), and these will be approached separately. It is readily apparent, however, that in many cases physicochemically and biochemically mediated mechanisms will operate side by side. In some instances, bioavailability may also be enhanced by the stimulation of intestinal lymphatic transport, and these studies will be addressed in a separate section. 

Ionization, pKa, and Aqueous Solubility Most drugs are weak acids or bases. It is important to note the relationship between the pKa of the compound and the absorptive environment. Delivery systems that are dependent on diffusion or dissolution will likewise be dependent on the solubility of drug in the aqueous media. Since drugs must be in solution before they can be absorbed, compounds with very low aqueous solubility usually have the oral bioavailability problems because of limited GI transit time of the undissolved drug particles and they are limited at the absorption site. Unfortunately, for many of the drugs and bioactive compounds, the site of maximum absorption occurs at the site where solubility of these compounds is least. 

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