Quantitative analysis of in vitro compatibility of binary and ternary mixtures of nitroimidazole and macrolides in combination with omeprazole using a calorimetric technique.

In the present study, in vitro interactions between nitroimidazoles, macrolides and omeprazole in binary and ternary mixtures were examined by measuring their enthalpy of solution (delta(sol)H) using a calorimetric technique. A comparison of the enthalpy of solution of the pure drugs with those of binary and ternary mixtures at pH 2 and 6 was made to indicate the magnitude of interaction between them. The delta(sol)H for all the nitroimidazoles is endothermic at pH 2 and 6 but both the macrolides show exothermic behavior, whereas the enthalpy of solution of omeprazole changes from -40.52 to 4.35 kJmol(-1) as the pH changes from 2 to 6. The results have been quantified by determining the excess enthalpy of solution for both binary and ternary systems. The small deviations from ideality for all the binary systems are attributed to various non-bonding interactions between different functional groups on both the drug molecules. The results suggest compatibility of drug pairs in their binary mixtures. However, ternary mixtures show somewhat larger interactions. The magnitude of interaction enthalpy of a ternary mixture comprising tinidazole, clarithromycin and omeprazoles which are available as a marketed kitshas been calculated to be significant, suggesting that the three drugs cannot be co-formulated.

Microcalorimetric evaluation of the in vitro compatibility of amoxicillin/clavulanic acid and ampicillin/sulbactam with ciprofloxacin.

Solution calorimetric technique has been used to determine the compatibility of binary and ternary systems of ampicillin trihydrate (AMP), sulbactam sodium (SS), amoxicillin trihydrate (AM), potassium clavulanate (PC) and ciprofloxacin hydrochloride (CP). The enthalpy of solution (DeltasolH) were obtained over a wide range of composition in the pH range 2-9. For all the pure drugs the DeltasolH is endothermic in nature. The molar enthalpies of interaction of binary (DeltaHbi.E) and ternary (DeltaHter.E) mixtures of the drugs in aqueous buffers have been determined. The DeltaHbi.E for all binary systems is negative and pH dependent (maximum pH 6-8) indicating the interaction among charged species of the drugs. In case of binary systems with CP the magnitude of DeltaHbi.E indicate strong interactions. The variation and magnitude of DeltaHbi.E for the systems is discussed in terms of hydrogen bonding and van der Waal's interaction in the solution. The interaction parameter for ternary systems (A) is positive indicating repulsive interaction among the drugs. The coefficients hi's calculated from Redlich-Kister equation for binary systems (DeltaHbi.E) and ternary interaction parameter (A) were used to predict the compatibility of the marketed formulations in pH range studied.

Ion chromatographic determination of cyanide released from flaxseed under autohydrolysis conditions.

Flaxseed is increasingly being used in some food products because of its high content of alpha-linolenic acid and dietary fibre. However, flaxseed contains cyanogenic glycosides which release toxic hydrogen cyanide in the presence of water (autohydrolysis). A method for estimation of cyanide in flaxseed under these conditions is described. The determination is carried out by homogenizing the sample with water, letting it stand, filtering it through a membrane and then injecting the filtrate into an HPLC system consisting of an anion exchange column and an electrochemical (amperometric, oxidation) detector. The homogenate is analysed at various intervals until a maximum value of cyanide is observed. The cyanide content of ten cultivars of flaxseed, when analysed by this method, was found to range from 124 to 196 micrograms/g. The release of cyanide showed a maximum at about 3 h of hydrolysis. Virtually no cyanide was detected on boiling the homogenate or the flaxseed before determination.

Mammary transfer and metabolism in the rat of halogenated fatty acids of halogenated olive oil.

To assess possible incorporation of halogenated fatty acids into the neonate via the milk, a 4-day study was carried out in which lactating Wistar rats were orally dosed with either brominated olive oil (BOO) (0.6 g/kg body wt/day) or chlorinated olive oil (COO) (0.4 g/kg body wt/day) for the first 4 days. On days 1-5 inclusive 2 pups per litter were sacrificed and the stomach curd and livers analyzed for halogenated fatty acids by gas liquid chromatography (GLC). On day 5 all dams also were sacrificed and their livers and adipose tissue similarly analyzed. With BOO, brominated fatty acids (bfa) accumulated in both the milk lipids and neonate liver lipids, and appeared to plateau on day 4 at levels of 2% and 5% respectively. In contrast to the BOO in which approximately 100% of the bfa was dibromostearic (DBS), the milk bfa comprised 79% (DBS), 9% dibromopalmitic (DBP) and 12% dibromomyristic (DBM) acids, suggesting maternal metabolism to the shorter chain brominated acids. In the neonate liver lipids the bfa composition was 47% (DBS), 12% (DBP) and 41% (DBM), suggesting either further metabolism in the neonate and/or preferential accumulation of the shorter chain brominated acids. The analysis of maternal tissue indicated very low bfa residues, contrary to previous studies in non-lactating rats. Similar results were obtained with COO.