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The present investigation deals with the formulation, optimization and evaluation of sodium alginate based In situ gel of Clarithromycin and Metronidazole Benzoate. Sodium alginate used as a polymer and CaCO 3 was used as a cross-linking agent. The In situ formulation exhibited well, viscosity, drug content and sustained drug release; this study reports that oral administration of aqueous solutions containing sodium alginate results in formation of In situ gel, such formulations are homogenous liquid when administered orally and become gel at the contact site. The results of a 3 2 full factorial design revealed that the concentration of sodium alginate and concentration of CaCO 3 significantly affected the dependent variables Q 1 , Q 12 and T 80 . These In situ gels are, thus, suitable for oral sustained release of Clarithromycin and Metronidazole Benzoate.

The oral bioavailability of many lipophilic drugs is known to increase when coadministered with fatty meals. Although such a phenomenon is typically ascribed to increased solubilization and absorption of drug, in some cases this increase in systemic exposure may be in part due to the influence of lipids on the presystemic metabolism of the affected drug. Oral lipids on their absorption may interfere with the drug metabolizing enzymes expressed in the small intestine and/or liver. Fatty acids incorporated in dietary triglyceride can modulate the expression and activity of drug metabolizing enzymes within the small intestine. Lipoproteins, which are the major carriers of lipids in the systemic circulation, can become associated with lipophilic drugs. Such a combination may influence the metabolism of lipophilic drugs through limiting their uptake into the cells thereby decreasing their metabolism. In a contrary manner, an increased uptake and metabolism of lipoprotein-bound drug may be facilitated by lipoprotein receptors mediated uptake. The components of lipoproteins may also modulate the expression or activity of hepatic and extrahepatic drug metabolizing enzymes.

Experimental hyperlipidemia has shown to decrease cytochrome P450 3A4 and 2C11 expression and to increase liver concentrations and the plasma protein binding of halofantrine (HF) enantiomers. The present study examined the effect of hyperlipidemic (HL) serum on the metabolism of HF enantiomers by primary rat hepatocytes. Hepatocytes from normolipidemic (NL) and HL (poloxamer 407 treated) rats were incubated with rac-HF in cell media with or without additional rat serum (5%). In those incubations with rat serum, the hepatocytes were preincubated or coincubated with serum from NL or HL rats. Rat serum-free hepatocyte incubations served as controls. Stereospecific assays were used to measure HF and desbutylhalofantrine (its major metabolite) enantiomer concentrations in whole well contents (cells + media). Concentrations of desbutylhalofantrine were not measurable. The disappearance (apparent metabolism) of (-)-HF exceeded that of antipode, but HF metabolism did not differ between hepatocytes from NL and HL rats. Coincubation of HL rat serum with NL hepatocytes caused a significant decrease in the disappearance of (-)-HF, whereas in HL hepatocytes, a substantially decreased apparent metabolism was noted for both enantiomers. Compared with NL serum, (-)-HF disappearance was significantly lowered upon preincubation of NL hepatocytes with HL serum. A combination of factors including diminished drug metabolizing or lipoprotein receptor expression, and increased plasma protein binding in the wells, may have contributed to a decrease in apparent metabolism of the HF enantiomers in the presence of lipoproteins from HL rat serum.