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Abstract

The role of a bile salt (sodium taurocholate) and lipolysis products (monoglyceride and fatty acid) in the intestinal absorption of a poorly water-soluble drug, diazepam, was investigated. Absorption rates and bioavailabilities were determined with the in situ rat gut technique of Doluisio et al. and analyzing the diazepam concentrations in the luminal solution, intestinal membrane, blood and lymph. The absorption rate constant of diazepam decreased with the increase in bile salt concentration. Thus, although the bile salt increased the solubility of diazepam, the net effect was a decrease in apparent diazepam absorption rate. On the other hand, the lipolysis products incorporated in the bile salt micelles increased the solubility of diazepam without affecting the absorption rate constant, and as a result the apparent absorption rate of diazepam increased. In addition, the solubilized diazepam was absorbed almost uniformly throughout the small intestine. The drug solubilized in mixed micelles of bile salt-lipolysis products was not absorbed through the lymphatic system along with the lipolysis products, rather it was absorbed directly into the blood. The possible mechanism of the effect of dietary fat in the absorption of drug is discussed.

Solubilities and intrinsic dissolution rates of sulphamethoxazole and trimethoprim

“…1). Somewhat similar experimental data have been found recently for papaverine hydrochloride (Serajuddin & Rosoff 1984) and phenazopyridine hydrochloride (Serajuddin & Jarowski 1985). 1).…”

“…A simple relationship between solubility and dissolution rate was not observed.There has been interest in the solubilities and dissolution profiles of weak bases and their hydrochloride salts in the presence of buffers and in hydrochloric acid solutions (Miyazaki et a1 1979: Serajuddin & Rosoff 1984Serajuddin & Jarowski 1985). Sulphamethoxazole was evaluated in buffers of ionic strength 0-5 mol dm-3 over the pH range 0.45-7.8 and at 25, 32 and 37 "C. The minimum solubility of sulphamethoxazole was 28-1 mg/100 mL at pH 3-22 and 25 "C. Solubilities increased significantly with both increased and decreased pH.…”

“…There has been interest in the solubilities and dissolution profiles of weak bases and their hydrochloride salts in the presence of buffers and in hydrochloric acid solutions (Miyazaki et a1 1979: Serajuddin & Rosoff 1984Serajuddin & Jarowski 1985). Those studies have reported unusual pH solubility characteristics, frequently associated with large changes in measured solubilities over a narrow pH range.…”