Solubilized drug

Yalkowsky, S.H. andValvani, S.C. Precipitation of solubilized drugs due to injection or dilDtvag,... 

Paclitaxel Tarretal. (1987) Triacetin emulsion to solubilize drug, alternative to surfactants, and cosolvents... 

It should be realized that if emulsions are used strictly to solubilize drug, the use of this formulation approach brings the following challenges ... 

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... 

One practical use of a buffer is to simply maintain the pH of the system over time. For pH solubilized drugs, another practical use of a buffer is to reduce or eliminate the potential for precipitation of the drug upon dilution. It has been shown that drug precipitation upon intravenous injection has been linked to phleb-itis.f As shown through the previous discussion, the solubility of a drug can be increased exponentially with pH alteration. However, it also then follows that the solubility can decrease exponentially with pH alteration. If a pH solubilized formulation is diluted with a medium by one half, then the drug concentration will... 

Cosolvents can be a powerful tool by which to solubilize drugs. For a given cosolvent selected, it is clear that the degree of solubilization attained for any solute is directly proportional to the octanol/water partition coefficient of that solute. However, as with pH solubilization, solubilization through cosolvents is logarithmic, and as a result there is the potential for precipitation upon dilution. 

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... 

One of the most important applications of micellization in the context of pharmaceuticals is their ability to solubilize drugs of poor aqueous solubility. 

Kubis A, Jadach W, Malecka K. Studies on the release of solubilized drugs from ointment bases. Pharmazie 1984 39 168-170. 

Calculate the amount of cyclodextrin-solubilized drug spectro-photometrically, by measuring its absorption at 256 nm, and constructing an appropriate calibration curve, ftom solutions of known drug concentration. 

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... 

Figure 17 (A). A two-dimensional representation of an amphipathic dendrimer, with both carboxylic acid groups and alkyl chains, resulting in a hydrophilic and hydrophobic hemisphere each. In solution, this feature will encourage self-association. (B). An amphipathic polyalkyl dendron prepared by Al-Jamal et al. (97), which forms dendrisomes, vesicular structures, shown in (C), capable of solubilizing drugs. In the diagram the hydrophilic interior comprising branched lysine chains is shown. The bar represents 200 nm.

The different chemical solutions to solubilizing problems discussed in this chapter reveal that in many cases the chemical transformation used also improves the activity profile of the parent molecule. This can be due to purely pharmacokinetic factors such as a better resorption from the organism and faster transport and diffusion. These factors explain also why solubilized drugs are generally faster eliminated and therefore show fewer symptoms of toxicity. But the pharmacological profile also can be affected. Chlorpromazine, for example (Figure 38.26), has neuroleptic properties, whereas the parent phenothi-azine possesses anthelminthic properties. In this example, the attachment of the basic moiety has totally modified the pharmacological profile. However, the replacement of the basic moiety by its carboxylic counterpart yielded a compound totally inactive as neuroleptic (C. G. Wermuth, unpublished result). 

TABLE 39.5 Compositions of Cosolvent-Solubilized Drug Products... 

TABLE 39.8 Compositions of Surfactant-Solubilized Drug Products Containing Phytomenadione... 

Stable in the blood to alter the pharmacokinetics of the solubilized drug. They are able to circulate for prolonged periods and to deliver more of the drug to tumor tissue when compared with administration of the drug in solution. 

Solubilizers (e.g., organic solvents, detergents, Pluronics) are often used to solubilize drugs in aqueous solution without considering their effects on biological systems, such as (i) lipid membranes and (n) multidrug resistance (MDR) efflux transporters (e.g., Pgp or MDRl). 

Villiers MM, Tiedt LR. An analysis of fine grinding and aggregation of poorly solubile drug powders in a vibrating ball mill. Pharmazie 1996 51 564-567. 

Therefore, micelle-forming surfactant molecules (e.g., SDS) will be present in three different forms, namely, on the lipid surface, as micelles, and as monomeric surfactant molecules in solution. Lecithin will form liposomes, which have also been detected in nanoemulsions for parenteral nutrition [77], Mixed micelles have to be considered in glycocholate/lecithin-stabilized and -related systems. Micelles, mixed micelles, and liposomes are known to solubilize drugs, and are therefore attractive alternative drug-incorporation sites (especially with respect to the low incorporation capacity of lipid crystals). 

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