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The kinetics of alkaline hydrolysis of benzocaine (ethyl p-aminobenzoate), n-butyl p-aminobenzoate, and ethyl p-n-butylaminobenzoate in the presence of a nonionic surfactant (polyoxyethylene 24 monocetyl ether) were investigated. The influence of the nonionic surfactant on the solubility and on the wavelength of maximum absorbance in the UV portion of the spectrum of the three compounds was also studied. At surfactant concentrations above thecmC, the rate of hydrolysis of the esters is decreased, the solubility is enhanced, and there is a bathochromic shift in the wavelength of maximum absorbance. As a result of the investigation, the partition coefficients of the compounds between the micellar phase and the aqueous phase, the location of the compounds within the micellar phase, and the hydrolytic rate constants within the two phases were determined. It was concluded that benzocaine and the homologs are probably associated with the polyoxyethylene portion of the micelle and that the observed change in the rate of hydrolysis can be attributed to both a decrease in the rate of hydrolysis and an increase of solubility within the micellar phase.

p-Aminosalicylic acid, which exists in four ionic forms and whose decarboxylation is well known, was used as a model drug to investigate the effects of surfactants with different charges on its stability. The greatest reduction in the rate of decarboxylation at 50 °C occurred when the charge on the micelles was opposite to that of the charge on the drug or when both the drug and the micelle had a neutral charge. Thus, at the highest surfactant concentration, 3 or 5% (w/v), there was a 59% reduction in the rate at pH 2.68 in the presence of the nonionic surfactant polyoxyethylene 24 monocetyl ether, 69% reduction in the rate at pH 4.88 in the presence of the cationic surfactant hexadecyl trimethylammonium bromide, and a 43% reduction at pH 1.01 in the presence of the anionic surfactant sodium cetyl sulfate. The decrease in the rate of decarboxylation was attributed to the partitioning of the drug into the micelles, which provided a phase for improved stabilization. Partition coefficients and rate constants for decarboxylation of the drug inside the micelles were calculated.

Phase diagrams were prepared to indicate the region of microcapsule formation for the following system: cellulose acetate phthalate, light mineral oil, acetone: 95% ethanol solvent, and sorbitan monooleate. The microencapsulation of pharmaceuticals having widely different solubility properties was carried out. Various factors affecting microencapsulation, namely trituration, order and time of addition of the pharmaceutical, core size, and the core to coat ratio, were investigated. The evidence for a mechanism of microencapsulation is also presented. The phase diagrams showed that microcapsules readily formed when the cellulose acetate phthalate concentration was in the 0.93–3.85% range and the polymer solvent concentration was in the 7–16% range. Aggregation of microcapsules was minimized at low solvent concentrations. Pharmaceuticals could be microencapsulated regardless of their solubility in the polymer solvent or hardening liquid. The size of the microencapsulated pharmaceutical increased as the coreicoat ratio increased to a maximum of 1.5:1. There is an upper size limit of the pharmaceuticals which can be coated.