Drug solubilization

Weiner, A. L. (1987). Lamellar systems for drug solubilization, in Liposomes From Biophysics to Therapeutics (M. J. Ostro, ed.), Marcel Dekker, New York, pp. 339-369. 

One potential risk that formulators run when using cosolvents as drug solubilizers is the possibility of vehicle toxicity. Each cosolvent is characterized by an acceptable concentration range, which cannot be exceeded without incurring biological damage. To avoid the requirement for in vivo testing, several in vitro models have been advanced to evaluate the relative safety of cosolvent excipients. The most useful in vitro procedure follows the hemolysis of red blood cells, which has been correlated with in vivo animal tests [87,88]. 

Wiedmann TS, Bhatia R, Wattenberg LW (2000) Drug solubilization in lung surfactant. J Control Release 65 43 47. 

Figure 6 Theoretical maximum drug solubilization by different CDs at their maximum water solubilities (assuming 100% 1 1 complexation). Abbreviations. CDs, cyclodextrin HP, hydroxypropyl SBE, sulfobutylether.

Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. I. Drug solubilization and stabilization. J Pharm Sci 1996 85(10) 1017. 

In order to overcome the main limitations of the impregnation processes, connected to the limited solubility of the compounds in the supercritical fluids, Perman [68] proposed an alternative method. A supercritical impregnation process was coupled with a liquid solvent (preferentially water) to enhance the drug solubilization. The system composed of a liquid drug solution and the polymeric support was pressurized with the supercritical fluid. Consequently, the swelled polymer allows rapid diffusional transport of the solute into the polymeric substrate. In different examples, bovine serum albumin microspheres were impregnated with insulin, trypsin and gentamicin (see Table 9.9-5). 

Loftsson, T. and M. Brewester(1996). Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilizationJ. Pharm. Sci., 85 1017-1025. 

Microemulsions, and Lipid-Based Drug Delivery Systems for Drug Solubilization and Delivery—Part I Parenteral Applications... 

Challenges with Emulsion Formulations for Drug Solubilization and Delivery. 215... 

Drug solubilization and delivery using emulsions does not lead to undesirable changes in its chemical stability, efLcacy, or toxicity. 

A Representative List of Experimental Studies Exploring Emulsion System for Drug Solubilization... 

All-trans-retinoicacid (ATRA) Hwang et al. (2004) Emulsion formulation enhanced drug solubilization and stabilization maintained antitumor activity... 

CHALLENGES WITH EMULSION FORMULATIONS FOR DRUG SOLUBILIZATION AND DELIVERY... 

Constantinides, P.P, Tustian, A., and Kessler, D.R. (2004)Tocol emulsion for drug solubilization and parenteral delivery.Adv. Drug Deliv. Rev., 56 1243-1255. 

Kaukonen, A.M. et al. (2004) Drug solubilization behavior durimgitro digestion of simple triglyceride lipid solution formulationsPharm. Res., 21 245-253. 

General Development Procedure for a Micellar Drug Solubilization System. 294... 

Florence (1983) provide a comprehensive reference for the use of surfactants in drug formulation development. The treatment by Florence (1981) of drug solubilization in surfactant systems is more focused on the question at hand and provides a clear description of surfactant behavior and solubilization in conventional hydrocarbon-based surfactants, especially nonionic surfactants. This chapter will discuss the conventional surfactant micelles in general as well as update the reader on recent practical/commercial solubilization applications utilizing surfactants. Other uses of surfactants as wetting agents, emulsiLers, and surface modiLers, and for other pharmaceutical applications are nc emphasized. Readers can refer to other chapters in this book for details on these uses of surfactant Polymeric surfactant micelles will be discussed in Chapter 13, Micellization and Drug Solubility Enhancement Part II Polymeric Micelles. 

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