Miscellaneous formulations and the influence of surfactants

Evidence for increased transport of C-labelled nitrogen mustard N-oxide through rat ascites hepatoma cell membranes by polysorbate 80 [164] and the recent observation that this surfactant can increase methotrexate uptake into the brain [82a] gives rise to hope that surfactants can play a useful role in modification of drug action in specialized forms of treat- 

The manner in which the formulation of THC affects the biological performance has been examined by two groups [168, 169]. Polysorbate 65-sorbitan monolaurate mixtures appeared to confer a longer duration of action by the intraperitoneal or subcutaneous route when compared with a PVP suspension and polysorbate 80 dispersion. Contrary to these findings, Sofia et al. [169] find 1 % polysorbate 80 to be a poor vehicle for oral, s.c., i.p. or i.v. administration producing inadequate results when compared to a PVP dispersion or a dispersion in propylene glycol. The most suitable vehicle did, however, contain 1 % polysorbate. The divergent opinion no doubt arises from the fact that the preparations are dispersions or emulsions and their mode of manufacture differs from laboratory to laboratory. Particle size and stability will thus vary. 

Propylene glycol and 20 % Cremophor EL have been compared as vehicles for diazepam [170] in view of the number of reports of thrombophlebitis associated with intravenous diazepam. The Cremophor vehicle caused significantly less postinjection thrombophlebitis possibly because it prevents the precipitation of the drug substance at the site of injection by its solubilizing effect. Ease of injection 

It is often assumed that drug solutions must be the most bioavailable form of the drug, but solutions of drugs poorly soluble at tissue pH will precipitate at the site of injection and subsequently release from the site might be slow. Precipitation may also occur if the drug is solubilized in a mixed solvent. In the presence of surfactant, as solubility is in most cases a linear function of surfactant 

Complication (right hand) (right hand) (left hand) 

---