Solubilization techniques

When delivered parentally or orally, a drug in solution is more rapidly bioavailable compared to a solid dosage form. The cosolvent approach also has some limitations as pointed out for other solubilization techniques. When solubilization of a drug is achieved by use of cosolvent, it must meet certain requirements, such as nontoxicity, compatibility with blood, nonsensitizing, nonirritating, and above all physically and chemically stable and inert. 

In some cases, low drug solubility may make some delivery platforms better candidates than others. Application of solubilization techniques enables design and development of oral MR dosage forms for poorly water-soluble drugs and can provide more choices and options in designing such a delivery system. 

Acceptable precision in most instances, reported as RSDs, usually range from 0.1 percent to slightly higher than 20 percent, with the most frequent value centered at 5DIO percent. RSD is only an informative value and does not allow the solubilization techniques to be distinguished. 

The solubilization technique should be used more frequently in combination with atomic spectrometric methods. Further research to improve its analytical performance in terms of LoDs, precision, and accuracy is required. 

With respect to selecting cosolvents, one should consider drug polarity and solvent polarity. Usually the solvents include glycerol, propylene glycol, and ethanol. Other solubilization techniques such as complexation and surfactants can also be used to enhance the solubility of the drug [36]. However, the solubilization techniques used in preclinical testing may not be same as the final formulation used in clinical studies and marketing. 

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. 

Table 4 shows comparison of the magnitude of solubility increases associated in general with various solubilization techniques. 

The solubilization techniques for injectable formulations are similar to those in oral formulations and include pH adjustment, mixed aqueous/organic cosolvents, organic solvent mixtures, cyclodextrin com-plexation, emulsions, liposomes, polymeric gels, and combinations of techniques. " Molecules that are non-ionizable, lipophilic, and non-polar are challenging to formulate owing to their low water solubility and no effect of pH on solubility. Examples include paclitaxel, docetaxel, cyclosporin A, etoposide, loraze-pam, tacrolimus, testosterone enanthate, and halo-peridol decanoate, and they are all solubilized in non-aqueous solutions composed entirely of organic solvent(s), which are usually but not always diluted prior to administration. 

Winnike R. Solubility Assessment in Pharmaceutical Development, Practical Considerations for Solubility Probling and Solubilization Techniques. AAPS Short Course on Fundamentals of Preformulation in Pharmaceutical Product Development, Nashville, TN, Nov. 5, 2005. 

In addition to their use in the in situ induction of conformational transitions, switch-peptides (O-acyl isopeptides) may serve as alternative solubilizing technique in peptide synthesis [207-214]. The elaboration of these concepts, notably the rational design of dynamic pharmacophores as new type of therapeutically useful compounds, is the subject of our current research. 

L. Lilge, C. O Carroll, B.C. Wilson (1997). A solubilization technique for photosensitizer quantification in ex vivo tissue samples. Journal of Photochem. and PhotobioL, B39, 229-235. 

Solid dispersion is defined as the dispersion of drug molecules in a solid matrix consisting of either a small molecule or polymer. It is an established and well-explored solubilization technique for poorly water-soluble drugs. Solid dispersions are mainly used to enhance the solubility and bioavailability of poorly water-soluble drugs. 

Solubility is of great importance in pharmaceutical systems since a drug must be dissolved before it is absorbed. When the drug absorption process is limited by dissolution, enhancing solubility can increase dissolution rate and in this way improve bioavailability.In addition to the dissolution rate, the ability to dissolve the therapeutic dose of the drug and the selection of solubilization techniques are critical for product development. 

For low molecular weight surfactants, the CMC, as well as the CMT, can be determined by various scattering techniques (SLS, SAXS,...) by fluorescence or dye solubilization technique, by... 

In general, reactions in which at least one of the reacting compounds is insoluble in water can be either homogenized by the addition of as much as possible of a suitable water-miscible cosolvent, or carried out in heterogeneous systems, using, as was noted above, (i) phase-transfer, (ii) phase-separation, or (iii) solubilization techniques. 

Lilge L et al, A solubilization technique for photosensitizer quantification in ex vivo tissue samples. 

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