Biomedical subjects

A M Molokhia

Publications and source records attributed to A M Molokhia.

6 recordsLinked to original sources

PubMed1984

Effect of storage on the bioavailability of cephalexin from its capsules.

Three brands of locally available cephalexin capsules were stored in paper bags at 40 degrees C/90% relative humidity. Samples were taken at different time intervals and tested for the effect of storage on disintegration, dissolution and drug content for up to 70 days. Bioavailability testing was carried by administering the capsules to four volunteers before storage and after 70 days of storage. Two brands (A and B) showed increase in disintegration time associated with decrease in the rate of dissolution. The third brand (C) showed similar effect but later on irregular disintegration and dissolution were observed. Such behavior was found to be a result of storage effect on the capsule shell. No effect on drug content was observed for brands A and B but significant loss of activity was observed with some samples of brand (C). Bioavailability testing based upon urine analysis for excreted drug indicated that the rate but not the extent of drug absorption for brands A and B decreased by storage. The results with brand C showed serious fluctuations in absorption after storage for more than 25 days. These findings point out to the importance of proper formulation and protection of solid dosage forms handled in places where high temperature and humidity conditions are likely to exist.

Biological Availability↗

PubMed1981

Phenobarbital solubility in propylene glycol-glycerol-water systems.

Phenobarbital solubility in various binary and ternary propylene glycol-glycerol-water solvent systems was determined. Phenobarbital concentrations several times those of the ethanol-containing USP and BPC elixirs were obtained. From log solubility-solvent composition plots, a general equation was developed for phenobarbital solubility prediction in propylene glycol-water, glycerol-water, and propylene glycol-glycerol-water solvent systems. Solubility predictions using another equation, based on linear log solubility-dielectric constant relationships, were limited by the need to use different constants for different solvent blends. Heats of solution for phenobarbital determined in selected solvent blends as well as in USP and BPC elixirs varied within a very narrow range, suggesting similar solute-solvent interactions.

Glycerol↗

PubMed1977

Dissolution kinetics of cholesterol in simulated bile I: Influence of bile acid type and concentration, bile acid-lecithin ration, and added electrolyte.

A physical model approach was utilized to investigate cholesterol monohydrate dissolution kinetics in simulated bile. The static pellet method and the Berthoud theory were employed to assess the contributions of the diffusion-convection mass transfer resistance and those of the interfacial resistance to the overall kinetics. For almost all situations studied, the interfacial resistance was the dominant rate-determining factor. The effects of four bile acids and their concentrations, the bile acid-lecithin ratio, and the added electrolytes and their concentrations on the interfacial resistance were examined. The results were correlated with those obtained with human bile samples, and the indications were that the kinetics of cholesterol dissolution in bile may be explainable on the basis of the principal bile acids, lecithin, and the electrolytes in the bile.

Bile↗

PubMed1977

Dissolution rates of model gallstones in human and animal biles and importance of interfacial resistance.

Cholesterol monohydrate dissolution kinetics in human gallbladder bile were studied to determine the magnitudes of the in vitro dissolution rates, the rate resistances in human gallbladder bile, and the extent that the interfacial resistance is the rate-determining factor. Dissolution rate studies also were conducted using human duodenal bile and animal bile for comparison. The dissolution rate resistance, R, ranged from 10(4) sec/cm for chicken bile to 10(4)-10(6) sec/cm for human bile. Interfacial resistance was the rate-determining factor for essentially all results. Where chemical composition data were obtained, the R values for the human bile samples were consistent with predictions made from the simulated bile studies. In two human gallbladder specimens having low bile acid-lecithin molar ratios (i.e., 2.9 and 2.3), very high R values of 1.9 X 10(5) and 4.1 X 10(5) sec/cm were found. These values were in good agreement with the findings in the simulated bile studies and suggest that stone dissolution in patients with low bile acid-lecithin ratios may proceed very slowly, even when the bile is highly undersaturated with respect to cholesterol.

Animals↗

PubMed1977

Cholesterol gallstone dissolution rate accelerators I: Exploratory investigations.

Various compounds that might function as cholesterol gallstone dissolution accelerators were studied. The dissolution rates of cholesterol monohydrate pellets in synthetic bile (116 mM sodium cholate-32 mM lecithin) containing the agent at various concentration levels were determined. In the absence of any dissolution rate accelerator, the dissolution kinetics for cholesterol previously were found to be interfacial resistance controlled, and the rates were around 20 times less than the diffusion-controlled rates in the present experiments. Primary, secondary, and tertiary amines and quaternary ammonium compounds were effective accelerators. When the alkyl chain lengths were long enough and/or when the agent concentrations were high enough, the dissolution rates generally approached diffusion-controlled rates. Steroidal amines generally had good activity. Anionic and nonionic surfactants had little or negative activity.

Amines↗

PubMed1976

Dissolution rate studies of cholesterol monohydrate in bile acid-lecithin solutions using the rotatingdisk method.

A physical model approach was used to investigate cholesterol gallstone dissolution kinetics in simulated bile. Critical experimental and theoretical investigations simulating in vivo conditions showed that, in the bile acid-lecithin solutions, there is a significant interfacial barrier for both cholesterol gallstone and cholesterol monohydrate pellet dissolution. In the present study, the rotating-disk dissolution method and the accompanying Levich theory were applied to assess the contributions of the diffusion convection mass transfer resistance and of the interfacial barrier to the overall kinetics. Cholesterol dissolution rates in bile acid solutions were about 2-20 times slower than diffusion-controlled rates depending upon the degree of agitation. As found in previous studies, these rates in the presence of sufficient concentrations of dissolution accelerators approached the theoretical diffusion-convection-controlled rates. To account for the much slower dissolution rates in bile acid-lecithin solutions, two possible kinetic interpretations were investigated. The first is based upon slow crystal-micellar solution interfacial kinetics, and the second is based upon a slow rate of cholesterol solubilization in the aqueous diffusion layer. For the latter, an analytical mathematical solution was obtained.

Benzoates↗