Benzocaine, solubilization

Hamid, I.A. and Parrott, E.L (1971). Effect of temperature on solubilization and hydrolytic degradation of solubilized benzocaine and homatropidepharm. Sci, 60, 901-906. 

Rubino, J.T., Blanchard, J., and Yalkowsky, S.H. Solubilization by cosolvents IV benzocaine, diazepam and phenytoin in aprotic cosolvamiter mixturesj. Parent. Sci. Technpl41, 172-176,... 

Fig. 7 Solubilization of benzocaine by dimethylaceta-mide, A, PEG-400, , PEG-200, , ethanol, x, methanol, propylene glycol and o, glycerin.

In aqueous alcoholic solutions, it very readily solubilizes essential oils. Aqueous solutions of hydrophobic drugs (e.g. miconazole, hexetidine, clotrimazole, benzocaine) can also be prepared with Cremophor EL. Cremophor EL has also been used as a solubilizing agent for drugs like cyclosporin A, paclitaxel, and cisplatin. Cremophor LLP is manufactured by purifying Cremophor EL and is therefore suitable for parenteral applications, e.g. Taxol preparations. In oral formulations, the taste of polyoxyl 35 castor oil (Cremophor EL) can be masked by a banana flavor. 

Rubino JT, Yalkowsky SH. Solubilization by cosolvents. Part 3. Diazepam and benzocaine in binary solvents. Bull Parenteral Drug Assoc 1985 39 106-111. 

Sheth and Parrott [244], in their study on the hydrolysis of esters, measured the solubility of benzocaine in a range of non-ionic surfactants including poloxamer 188. It was the least efficient, a Tetronic co-polymeric surfactant (Tetronic 908) having twice the solubilizing capacity. Tetronic is the proprietary name for the poloxamine series with the general structure,... 

Current interest in radiation sterilization of pharmaceuticals led Fletcher and Davies [142] to investigate the sensitivity of benzocaine to irradiation in aqueous solution. Cetrimide and polysorbate 80 protect the drug from the deleterious effects of a Co source at doses up to 0.3 M rad. However, ethanol, glycerol and polyoxyethylene glycol 200 when used as co-solvents at concentrations up to 40% were more effective [142] (Fig. 11.23) (equal concentrations of surfactant and co-solvent were not compared). These results emphasize the need to compare critically the different approaches to both solubilization and stabilization. High concentrations of surfactant, even non-ionic surfactant, are usually impracticable on the grounds of toxicity and thus the choice of solubilization technique cannot always be made on the basis of the physical chemistry of the competing methods. 

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