Drug solubilization surfactants

A. T. Florence, Drug Solubilization in Surfactant Systems, in Techniques of Solubilization of Drugs (S. H. Yalkowsky, ed.), Marcel Dekker, New York, 1981, pp. 15-89. 

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

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. 

Florence, A. T. 1981. Drug solubilization in surfactant systemiebhniques of Solubilization of Drqcpdited by S. H. Yalkowsky. New York Marcel Dekker, Inc. 

Any enhancing effect of surfactants on drug absorption appears to be related to increased drug solubilization, modification of mucosal permeability, or reduction of resistance of the unstirred water layer at the GI membrane surface. In general, unionic surfactants have little effect on membrane structure but cationic surfactants have been associated with reversible cell loss and loss of goblet cells. These effects must limit consideration of surfactants as absorption promoters, particularly for long term treatment. 

Elorence, A.T. Drug solubilization in surfactant systems. In Techniques of Solubilization of Drugs Yalkowsky, S.H., Ed. Marcel Dekker, Inc. New York, 1981 15-89. 

The choice of solubilization method will depend upon how efficiently the drug can be solubilized, stability in the system, and upon the biocompatibility of the vehicle for a given delivery route. For solid dosage forms, it may be possible to alter the solid phase to enhance dissolution. For parenterals, the four most commonly used techniques for solubilization are pH adjustment cosolvent addition micelle inclusion through surfactant addition and complexation. The following chapter is designed to summarize the theoretical as well as practical use of each of the above techniques. More extensive discussion on techniques for drug solubilization can be found in books dedicated to the subject. ... 

The main formulation challenge with HFA pMDI has been the poor solubility of the surfactants that were used in CFC products. Most pMDI formulations are suspensions of fine powder in propellant, and in order to obtain acceptable dose uniformity these suspensions usually require surfactants to stabilize them. The inability to use conventional surfactants has therefore led to a range of diverse formulation approaches. These encompass drug solubilization using cosolvents (Qvar is an example), new surfactants, coating particles with surfactant, and particle engineering (Fig. 3). However, as is the case with most... 

Co-solvents in metered dose inhalers were commonly used in CFG formulations to aid in drug solubilization. In HFA formulations, co-solvents continue this same function, but have additional benefits in the new systems, such as solubilization of other excipients. Vervaet and Byron discuss water solubility in the various propellants addressed here, where the addition of ethanol to the HFA system considerably increases the solubility of water (Vervaet and Byron, 1999). Likewise, ethanol was found to increase the solubility of several surfactants in HFA (Vervaet and Byron, 1999 Stein and Stefely, 2003). Suspension formulations using this technique (surfactant plus ethanol) must be made with caution however, as ethanol can also increase the solubility of the drug substance, potentially causing increased particle growth via Ostwald ripening. Nonetheless,... 

For liquid dosage forms of water-insoluble drugs, solubilization is an important tool in preformulation studies for the selection of surfactants. When... 

Drug Solubilization with Organic Solvents, Surfactants and Lipids 633... 

Cosolvents are often nsed in the formnlation of microemulsions to increase the solnbility of drug by cosolvency and to stabilize the dispersed phase. In addition to making the environment more hydrophobic by redncing the dielectric constant of water, cosolvents also increase the amount of molecularly dispersed snrfactant in the aqueous phase. Availability of free surfactant aids in drug solubilization by creating pockets of hydrophobic regions within the aqueous phase. " ... 

Recent years have witnessed an unceasing interest and substantial progress in drug solubilization by different techniques, such as complexaiion, use of surfactants and cosolvents, etc. (77). Hius, novel and more efficient ocular delivery systems for scarcely soluble drugs might be in store for the future. 

---