Solubilizers drug molecules

Water-miscible surfactant molecules contain both a hydrophobic and hydrophilic portion, and can solubilize many poorly water-soluble drugs. Surfactants can also self-assemble to form micelles once the surfactant monomer concentration reaches the critical micelle concentration. Thus surfactants can solubilize drug molecules by either a direct cosolvent elfect or by uptake into micelles. The non-ionic surfactants in commercially available solubilized oral formulations include polyoxyl 35 castor oil (cremophor EL), polyoxyl 40 hydrogenated... 

With the development of new dosage form technology in which control of drug release is achieved, it is conceivable that micellar systems will find some place because of the ability of the micellar phase to alter the transport properties of solubilized drug molecules. One can envisage the deliberate addition of surfactants to drug reservoirs to control the exit rate of drugs from polymeric devices. This will be explained in Chapter 7. 

The polar character of the liposomal core makes the encapsulation of polar drug molecules possible. Amphiphilic and lipophilic molecules are solubilized within the phospholipid bilayer according to their affinity toward the phospholipids. Participation of nonionic surfactants instead of phospholipids in the bilayer formation results in Niosomes . The term sphingosomes is suggested for vesicles from sphingolipids. However, the nomenclature is not consistent, and the term liposomes is used as a general term, although vesicles would be the better choice. 

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,... 

Nevertheless, solubilization still could be required for very insoluble molecules. Several approaches have been reported. Use of cyclodextrin as a complexation agent was shown to be effective and yielded both accelerated and pH-independent release.48 Further, in situ complexation between drug molecules and cyclodextrin in the matrix was encouraging because it would not require organic processing to render such complexation prior to matrix preparation. Recently, other approaches, such as incorporating... 

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. 

Not withstanding the use of nanoparticles for intravenous and topical applications, improvement in oral bioavailability is one of the most important contributions attained through nanotechnology. Molecules that are poorly water soluble may be poorly absorbed because of a lack of sufficient concentrations of solubilized drug. Formulations that are amorphous can overcome this by supersaturation of the dissolution medium allowing for greater absorption of the delivered dose. However, stability problems are significant for... 

Most oral formulations are solid tablets or capsules, but there are many solution formulations for oral administration that are filled into capsules, or are bulk solutions such as oral solutions, syrups, and elixirs. The reasons for pursuing a solubilized oral formulation include enhancing the oral bioavailability of a poorly water-soluble drug, a drug molecule that is an oil, a low dose drug (i.e., pediatric formulation, a measurable formulation for dose modification, a formulation for patients who cannot swallow tablets... 

Sulfobutylether-p-cyclodextiin (Captisol ) is one of newest excipients in pharmaceutical commercial formulations, is very safe, chemically stable, water-soluble, and is an excellent solubilizing drug delivery technology for molecules in which it forms an inclusion complex. An aqueous solution with 12%wt/v Captisol is isotonic, but formulations can contain as much as 30%wt/v Captisol. Ziprasidone mesylate, a rapid... 

Solubilization of a drug by incorporation into micelles may affect its stability.i In the micelle, the molecular environment of the drug molecules changes their proximity and orientation with respect to each other, which may affect activity. In a micelle, the drug molecules may be protected from attacking species such as hydronium or hydroxide ions and the stability of the drug may be increased. The difference in environment between the micellar and bulk aqueous phases may be such that reaction rates may be radically changed by the transfer of solute to micelles. Micellar systems may be used to deliberately alter the rates and directions of chemical reactions. ... 

It is well known that block copolymers in a selective solvent (a good solvent for one block but a non-solvent for the other) form a micellar structure through the association of the insoluble segments. In contrast with micelles formed from low molecular weight surfactants, block copolymer micelles dissociate slowly to free polymeric chains. They have a greater capacity for solubilizing aromatic molecules and express lower CMCs. The AB block copolymers are considered useful vehicles for hydrophobic drugs. 

Parenteral is defined as situated or occurring outside the intestine, and especially introduced otherwise than by way of the intestines —pertaining to essentially any administration route other than enteral. This field is obviously too broad for an adequate focus in one book, let alone one chapter. Many have nonetheless used the term synonymously with injectable drug delivery. We restrict ourselves to this latter usage. This would thus include intravenous, intramuscular, subcutaneous, intrathecal, and subdural injection. In this chapter we discuss the theoretical and practical aspects of solubilizing small molecules for injectable formulation development and will examine the role of surfactants and other excipients in more recent parenteral delivery systems such as liposomes, solid-drug nanoparticles and particulate carriers. 

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