In vitro release studies on drugs suspended in non-polar media II. The release of paracetamol and chloramphenicol from suspensions in liquid paraffin

Abstract

The release of paracetamol and chloramphenicol (water solubility 13 and 3.6 mg · g−1, respectively), suspended in liquid paraffin, to an underlying aqueous layer was investigated as a function of particle size (10–60 μm), concentration (0.5–6% m/m) and the presence of additives (DOSS-Na: di-(2-ethylhexyl) sodium sulphosuccinate and/or water) in the liquid paraffin. A hypothesis was formulated predicting the release to be independent of particle size, concentration and degree of coverage of the interface by particles, if the mass flow of the interface would exceed the dissolution rate of the particles at the interface. This limiting rate would approximate the intrinsic dissolution rate. The experimental results showed that for low concentrations the release was determined by the settling mass flow. With more concentrated suspensions the release was dissolution controlled and in general a good agreement with the proposed hypothesis was found.

Addition of water (0.01 or 0.05% m/m) to the suspensions increased the degree of agglomeration and reduced the degree of interfacial coverage, but did not change the release rate. The presence of 0.2% m/m DOSS-Na in the paracetamol suspensions did not influence the rate either, but in combination with water (0.01 or 0.05% m/m) an increase was observed; the particles did not stay at the interface during dissolution, but they fell through it as such. With chloramphenicol this happened already in the presence of 0.2% m/m DOSS-Na. Water addition enhanced this effect dramatically.