Spectrophotometric studies of a novel Gedunin-2-Hydroxypropyl- ß-cyclodextrin binary system.

BACKGROUND: Gedunin, a limonoid, is linked with antimalarial, anticancer and anti-allergic activities. This study was aimed at preparing an inclusion complex of gedunin and 2-hydroxypropyl-p-cyclodextrin (HBD) to increase solubility of-gedunin in polar solvents which will increase absorption and bioavailability in vivo and thus enhance pharmacological effects. MATERIALS AND METHODS: Gedunin was obtained from the hexane extract of Entandrophragma angolense heartwood by column and preparative thin layer chromatography. The structure was previously confirmed by spectroscopic means (NMR). The electronic absorption spectra data of the complexes formed between gedunin. and HBD in various solvents was determined using the UV-VIS spectrophotometer. The stoichiometry of inclusion was determined by Job's method of continuous variation. RESULTS: Evidence of interaction was observed between gedunin and HBD in the various solvents but gedunin and its complex with HBD exhibited sharp absorption bands in acetate buffer (pH 3.5).The spectrophotometric titrations showed curves with a single point of inflexion when the experiment was carried'out at 25°C (298 K) and 37°C (310 K). A stoichiometric ratio of 1:1 for complex formation was obtained. The formation constants (K,) obtained at 25°C and 37°C.were 9.539 x.10³ M⁻¹ and .1.853 x 104 M⁻¹ respectively. Thermodynamic considerations revealed hydrophobic interaction between gedunin and HBD. CONCLUSION: A stable inclusion complex of gedunin and HBD was formed at room and body temperature. This complex formation involved trapping of poorly soluble gedunin into the hydrophobic core of the cyclodextrin and may enhance the pharmacological activity of gedunin in vivo.

Lipid profile in an apparently healthy Nigerian population.

AIMS AND OBJECTIVES: To describe the pattern of lipid profile of members of staff of a tertiary education institution in South-West Nigeria with a view to assessing risk of cardiovascular disease among them. MATERIALS AND METHODS: One hundred and ninety three (193) members of staff of the Institution were involved in the study. Questionnaires were administered to obtain information on demographic characteristics and medical history of respondents. Weight, height and blood pressure of participants were measured and the Body Mass Index (BMI) calculated. Fasting plasma lipid profile parameters--Total cholesterol (TC), High Density Lipoprotein cholesterol (HDL-C) , Low Density Lipoprotein cholesterol (LDL-C) and Triglycerides (TG)) were also determined in all the participants using standard assay methods. RESULTS: Mean TC, HDL-C, LDL-C and TG were 4.04 mmol/L, 1.63 mmol/L, 1.98 mmol/L and 0.92 mmol/L respectively . Mean BMI was 25.98 kg/m2. Twenty-eight (14.5%) participants had mean cholesterol values e" 5.2 mM/L, 19 men had HDL values<1.0 mM/L and 28 women had HDL values<1.3 mM/L (making a total of 24.3% of the study population). Twenty (10.4%) had LDL cholesterol e"3.3 mM/L, while 14 (7.3 %) had triglyceride valuese" 1.7 mM/L. One hundred and thirty one (67.8%) participants had values of all lipid parameters within reference range while 62 (32.8%) had abnormality in 1 or more of the parameters. Sixty two participants (32.1%) were overweight while 45 (23.3%) were obese. Statistically significant differences were found when TG and BMI levels of male participants were compared with those of their female counterparts. Abnormalities in lipid profile parameters were found mostly in participants who were 40 years and above. Age of participants correlated positively with total cholesterol and LDL cholesterol levels while LDL-C levels correlated negatively with HDL levels. CONCLUSION: A significant proportion of the population had abnormality in one or more Lipid profile parameters, the most common being low HDL cholesterol levels. A considerable number of participants were also either overweight or obese. Most of the abnormalities in lipid profile were found in participants e" 40 years. The study underscores a need to sensitise members of the community to regular lipid profile check up .

The Metabolic Syndrome in an Elite African Community

Metabolic syndrome is a combination of metabolic disorders which increase the risk of developing cardiovascular disease and type 2 diabetes; two common causes of morbidity and mortality all over the world; with increasing incidence in sub-Saharan Africa. This study was carried out to determine the prevalence of metabolic syndrome in an elite Nigerian community and determine independent predictors of the condition. A cross-sectional study was designed involving 200 members of the community. They responded to a structured questionnaire on their demographic parameters as well as medical and drug histories. Fasting blood glucose; triglycerides; LDL-cholesterol; HDL-cholesterol and Total cholesterol were measured. Blood pressure; BMI and waist circumference were also measured. Using the IDF definition i.e presence of central adiposity and two of raised TG (?1.7 mm/L); reduced HDL (1.03 mm/L in men and 1.29 mm/L in women); raised blood pressure (130 mmHg systolic or 85 mmHg diastolic; or an antihypertensive drugs); and raised fasting blood glucose (5.6mm/L or previously diagnosed type 2 diabetes); a total of 35 persons were found to have metabolic syndrome. The commonest lipid abnormality found was reduced HDL levels. Raised BMI was a strong predictor (18). The study shows that while the prevalence of metabolic syndrome is low in the community; a large number of people have central obesity and high BMI. It is important for stakeholders to create awareness on the need to keep fit. There is also a need to carry out more studies on independent determinants of metabolic syndrome and seek to understand the pathways by which it develops; so as to be able to address it's far reaching implications

Experimental determination of the physicochemical properties of lumefantrine.

BACKGROUND: The physicochemical properties of lumefantrine, a first line combination medicine for the treatment of uncomplicated falciparum malaria have been determined experimentally rather than theoretically as a guide to understanding its disposition in human. METHOD: The solubility of lumefantrine in various organic solvents was evaluated by estimating the volume of solvent that completely dissolved 15 mg of the drug. Melting point determination was carried out using a melting point apparatus. Dissociation constant of the drug was determined potentiometrically in 0.1M perchloric acid and partition coefficient was by the method of Leo Hansch, using ratio of the concentration of organic to aqueous phase. RESULT: Lumefantrine has a melting point of 128-131 degrees C. Its solubility in selected solvents range from 0.013% in acetonitrile (very slightly soluble) to 7.5% in chloroform and dichloromethane (soluble), and it is practically insoluble (0.002%) in water. The ionization constant (pKa), determined in 0.1 M perchloric acid was found to be 9.35. The Log P lies in the range 2.29-3.52, confirming the lipophilicity of lumefantrine. CONCLUSION: The physicochemical properties of lumefantrine reveal that it is highly lipophilic, weakly basic and readily dissolves in non-polar and/or aprotic organic solvents. While these properties will favour its distribution across cellular membranes, the rate-limiting step will be at the dissolution-absorption stage which will require biopharmaceutical modifications.

Evaluation of antioxidant activity of Tetracarpidium conophorum (Müll. Arg) Hutch & Dalziel leaves.

This study evaluated the antioxidant activity as well as bioflavonoid content of the methanol and ethanol-water extracts of the fresh and dried leaves of Tetracarpidium conophorum. Antioxidant activity was determined by spectrophotometric methods using DPPH free radical, nitric oxide radical inhibition and ferric reducing antioxidant power assays. In addition, total phenolics, flavonoids and proanthocyanidin content were also determined. The ethanol: water extract of the dried leaves had the highest antioxidant activity with a 50% inhibition of DPPH at a concentration of 0.017 mg/mL compared to the standards, Vitamin C and Vitamin E with inhibition of 0.019 and 0.011 mg/mL, respectively. This extract also showed nitric oxide radical inhibition activity comparable to that of rutin, 54.45% and 55.03% for extract and rutin, respectively, at 0.1 mg/mL. Ferric reducing power was also comparable to that of ascorbic acid (281 and 287 µM Fe (11)/g, resp.) at a concentration of 1 mg/mL. The methanol extract of both the dried and the fresh leaves had higher phenolic, flavonoids and proanthocyanidin content than the ethanol:water extract. The study reveals that T. conophorum can be an interesting source of antioxidants with their potential use in different fields namely food, cosmetics and pharmaceuticals.

Hepatitis B viral markers in surface antigen negative blood donors: the need to look beyond antibody negativity.

BACKGROUND: The presence of Hepatitis B Virus (HBV) in blood that is Hepatitis B Surface Antigen (HBsAg) negative is considered a potential risk for transmission of hepatitis B virus infection. OBJECTIVE: To determine prevalence of antibodies to markers of hepatitis B virus infection in HBsAg negative prospective blood donors. METHODS: A structured questionnaire to assess prospective donor's demographic data and past medical history was administered to 457 consenting HBsAg negative subjects. All the subjects were also negative for antibodies to hepatitis C virus (HCV), human immunodeficiency virus (HIV) and syphilis. Their serum samples were tested for the presence of anti-HBc, anti-HBe, anti-HBs and HBeAg. RESULTS: Of the 457 samples tested, 20 (4.37%), 58 (12.69%), 1 (0.22%), and 1 (0.22%) were positive to anti-HBc, anti-HBs, anti-HBe, and HBeAg antibodies, respectively. Ten (50%) of those who were positive for HBc antibody were also positive to anti-HBe and anti-HBs. Similarly, two (3.4%) donors who were positive for anti-HBs were also positive for HBeAg and anti-HBe. Of the 20 who were anti-HBc positive, seven had tattoo/traditional marks on their body and one had previous history of blood transfusion. CONCLUSION: This study has shown that some potential blood units containing HBV are being transfused to patients unknowingly by screening for HBsAg only. Screening for other markers of hepatitis B virus may increase the rejection rate, but will reduce HBV transmission.

Effects of water extract of Hibiscus sabdariffa, Linn (Malvaceae) 'Roselle' on excretion of a diclofenac formulation.

The effect of beverages prepared from the dried calyx of the flowers of Hibiscus sabdariffa on the excretion of diclofenac was investigated using a controlled study in healthy human volunteers. A high pressure liquid chromatographic method was used to analyse the 8 h urine samples collected after the administration of diclofenac with 300 mL (equivalent to 8.18 mg anthocyanins) of the beverage administered daily for 3 days. An unpaired two-tailed t-test was used to analyse for significant difference observed in the amount of diclofenac excreted before and after administration of the beverage. There was a reduction in the amount of diclofenac excreted and the wide variability observed in the control with the water beverage of Hibiscus sabdariffa (p < 0.05). There is an increasing need to counsel patients against the use of plant beverages with drugs.

Novel determination of nabumetone, a cox-2 inhibitor precursor via its 4-carboxyl-2,6-dinitrobenzene diazonium (CDNBD) derived AZO dye.

A novel colorimetric determination ofnabumetone in tablets has been developed. The assay is based on chemical derivatization (aromatic ring derivatization technique) using newly developed 4-carboxyl-2,6-dinitrobenzene diazonium (CDNBD) ion as the chromogenic derivatizing reagent and resultant formation of azo dye.Optimization studies established an optimal reaction time of 10 minutes at 30 degrees C after mixing the drug/reagent mixture in a vortex mixer for 10 sec. A new absorption maximum (ë(max)) was found at 470 nm, which was selected as analytical wavelength. The assays were linear over 1-6 microg/ml of nabumetone and the optimal reaction required a 2:1 reagent/drug stoichiometric ratio. The developed method has a low limit of detection of 0.39 microg/ml, and is reproducible (1.81% RSD). It has been applied successfully to the assay of nabumetone tablets and is of equivalent accuracy (p > 0.05) with the official (B.P) HPLC method. The new method is simple, has the main advantage of employing a more affordable instrumentation and could find application in routine in-process quality control of nabumetone tablets.

Determination of physicochemical properties of halofantrine.

The physicochemical properties of halofantrine hydrochloride (HF HCl)--a phenanthrene methanol antimalarial, were determined practically in this study since such experimental values are still unknown. The solubility in different solvents were determined and found to be 0.67%w/v in methanol (slightly soluble); 0.4%w/v in both n-octanol and acidified acetonitrile (slightly soluble); 0.09%w/v (very slightly soluble) and less than 0.002%w/v in warm water (50 degrees C) (practically insoluble). Halofantrine hydrochloride was found to be practically insoluble in water (at room temperature), n-hexane and phosphate buffer solution of pH 7.4. The partition coefficient between n-octanol and water gave a log p in the range of 3.20-3.26 (mean 3.20 +/- 0.04) and this was at variance with the log P of 8.5 estimated theoretically in literature. The value also confirms the lipophilicity of HF HCl. The ionisation constant (pKa) determined in partly aqueous solvent (40% methanol) ranged between 8.10 and 8.20 (mean 8.18 +/- 0.05) and confirms the monobasicity of halofantrine. This value also differed from the theoretical estimation of 9.6. The values obtained confirm the often unpredictable and erratic absorption of HF HCl, which bears direct relationship to the physicochemical properties and support the need for better formulations with improved drug delivery potentials.