Stability of drugs in surfactant systems

Many of the investigations carried out on mechanisms of catalysis and inhibition in surfactant systems have employed model compounds. Such is the observed specificity of reactions that whatever understanding is gained from the work there can be little confidence in extrapolation of the results to complicated drug structures. This section of the chapter surveys some of the work which has been carried out with pharmaceuticals. A later section will consider the stability of surfactant molecules themselves. 

The aim in pharmaceutical formulations will be to reduce rates of degradation by appropriate choice of surfactant system, and to avoid surfactants which catalyse reactions. Cetomacrogol 1000 reduces the rate of hydrolysis of aspirin in its unionized state but does not stabilize the ionized form of the drug. Above a pH of about 3 it seems that only drug in the aqueous phase undergoes hydrolysis, so considering the micellar solution as a two-phase system [131] one can write 

If the reaction partially takes place in the micellar phase an additional term must be added as the total rate constant is now the sum of and the rate constant in micellar phase, km This leads to equations of the form. 

Relatively small increases in stability of chloramphenicol in polysorbate 80, Myrj 59, polysorbate 20 and Brij 35 have been observed on autoclaving [134]. Selection of a suitable concentration of polysorbate 80 and adjustment of solutions to pH 4.6 reduced to half the autoxidative degradation of methyl-prednisolone even in the presence of oxygen [135]. Contrary to electrostatic theories of stabilization the base-catalysed hydrolysis of procaine was inhibited by non-ionic, anionic and cationic micelles as shown in Table 11.10. The order of inhibition of hydrolysis was NaLS CTAB PLE NDB the order of partition coefficients (P ) was found to be NaLS CTAB NDB PLE (see table for abbreviations). 

The observed rate constants for hydrolysis of procaine in various surfactant 

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