Solubilized systems

Microemulsions or solubilized or transparent systems are very important ia the marketing of cosmetic products to enhance consumer appeal (32,41). As a rule, large quantities of hydrophilic surfactants are required to effect solubilization. Alternatively, a combination of a solvent and a surfactant can provide a practical solution. In modem clear mouthwash preparations, for example, the flavoring oils are solubilized in part by the solvent (alcohol) and in part by the surfactants. The nature of solubilized systems is not clear. Under normal circumstances, microemulsions are stable and form spontaneously. Formation of a microemulsion requires Httle or no agitation. Microemulsions may become cloudy on beating or cooling, but clarity at intermediate temperatures is restored automatically. 

AH Goldberg, WI Higuchi. Mechanisms of interphase transport II Theoretical considerations and experimental evaluation of interfacially controlled transport in solubilized systems. J Pharm Sci 58 1341-1352, 1969. 

AH Goldberg, WI Higuchi, NFH Ho, G Zografi. Mechanism of interphase transport I Theoretical considerations of diffusion and interfacial barriers in transport of solubilized systems. J Pharm Sci 56(11) 1432-1437, 1967. 

Excipients offer several possibilities and mechanisms. For microemulsions, Cremophor RH 40, Cremophor EL, and Solutol HS 15 act as surface active solubilizers in water and form the structures of micelles. The micelle that envelops the active substance is so small that it is invisible, or perhaps visible in the form of opalescence. Typical fields of application are oil-soluble vitamins, antimycotics of the miconazole type, mouth disinfectants (e.g., hexiditin), and etherian oils or fragrances. Solutol HS 15 is recommended for parenteral use of this solubilizing system and has been specially developed for this purpose. 

Solutol HS 15 is recommended for parenteral use of this solubilizing system and has been specially developed for this purpose. 

A drug molecule has to be water soluble to be readily delivered to the cellular membrane, but needs to be hydrophobic to cross the membrane (Thompson, 1997). Both properties can be utilized to develop various solubilization systems that can deliver water-insoluble drugs via various routes to the targets in humans. Through years of diligent and intelligent research by pharmaceutical scientists,... 

This is especially true for insoluble compounds in different solubilizing systems. The dependence of solubility on temperature will most likely change for different solubilizing systems, and therefore, needs to be studied carefully. 

SpeciLc problems exist with parenteral manufacture the most obvious being the need to ensure sterility. It is necessary to assess the effect that a heat sterilization process will have on a drug (e.g., pKg shift on heating) and on the formulation. Certain solubilization systems such as emulsions may not be suitable for autoclaving. 

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

Goto, A., R. Sakura, and F. Endo. 1980. Gel Jtration of solubilized systems. V. Effects of sodium chloride on micellar sodium lauryl sulfate solutions solubilizing alkylparabtfMsem. Pharm. Bull. 28 14-22. 

Leuenberger, H. and Kocova El-Arini, S., Solubilization systems-The impact of percolation theory and Fractal Geometry. InVWter-lnsoluble Drug Formulation, R. Liu (Ed.), Interpharm Press, Denver, Colorado, Chapter 16, 569-608 (2000). 

They are an attractive medium for polymerization a successful reaction of that kind retaining the structure would mean new and Interesting materials. Claims to such reactions have been made In several Instances from micellar structures to highly solubilized systems (9-13) with varied degree of success. 

In this paper, the results on solution and Interfaclal properties of a cationic celluloslcs polymer with hydrophobic groups are presented. Interaction of such polymers with added surfactants can be even more complex than that of "unmodified" polymers. In the past we have reported the results of Interactions of unmodified cationic polymer with various surfactants Investigated using such techniques as surface tension, preclpltatlon-redlssolutlon, viscosity, solubilization, fluorescence, electroklnetlc measurements, SANS,etc.(15-17). Briefly, these results showed that as the concentration of the surfactant Is Increased at constant polymer level significant binding of the surfactant to the polymer occurred leading to marked Increases In the surface activity and viscosity. These systems were able to solubilize water Insoluble materials at surfactant concentrations well below the CMC of polymer-free surfactant solutions. Excess surfactant beyond that required to form stoichiometric complex was found to solubilize this Insoluble complex and Information on the structure of these solubilized systems has been presented. 

During the last two decades, significant efforts have been made in the development of solubilization systems for poorly soluble drugs. As listed in Table 1, various methods have been explored to increase water solubilities of poorly soluble drugs. 

A preferred location of the solubilizate molecule within the micelle is largely dictated by chemical structure. However, solubilized systems are dynamic and the location of molecules within the micelle changes rapidly with time. Solubilization in surfactant aqueous systems above the critical micelle concentration offers one pathway for the formulation of poorly soluble drugs. From a quantitative point of view, the solubilization process above the CMC may be considered to involve a simple partition phenomenon between an aqueous and a micellar phase. Thus the relationship between surfactant concentration Cm and drug solubility Ctot is given by Eq. (3). 

At a concentration of 0.1 %, chlorocresol may be completely inactivated in the presence of nonionic surfactants, such as polysorbate 80. However, other studies have suggested an enhancement of antimicrobial properties in the presence of surfactants. Bactericidal activity is also reduced, due to binding, by cetomacrogol, methylcellulose, pectin, or cellulose derivatives. In emulsified or solubilized systems, chlorocresol readily partitions into the oil phase, particularly into vegetable oils and higher concentrations will be required for efficient preservation. ... 

In industry, several dendrimers are already being synthesized on a hundred kilogram scale. The hopes for effective solubilizing systems suitable for medical applications may, however, not be justified. Phenolic ether or polyamine compounds are both normally not biodegradable so that major problems are foreseeable. An alternative is the employment of hydrolysable polyesters. One such compound already reported, is the imperfectly hyperbranched dendrimer which is easily accessible via thermal self-condensation of 3,5-bis(trimethyl-siloxyjbenzoyl chloride. This one-step procedure leads to a dendritic polyester... 

Figure 22.1 Nanoparticulate-mediated drug delivery across the tight (a) and leaky (b) tissue barriers. In the case of nanocrystals and drug solubilization systems, the dissolution rate is increased and free drug permeates across the tissue barrier with the appropriate mechanism. The nanoparticulate-bound drug behaves differently. The nanoparticulates are too large for the direct transcellular permeation across the cells walls (I), for the paracellular diffusion through the tight tissue boundaries (a-l I), and for the active transport by membrane transporters...

Solubilizing Systems for Parenteral Formulation Development—Small Molecules... 

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