Preventive Effects of Curcumin Against Drug- and Starvation-Induced Gastric Erosions in Rats.

Preventive effects of curcumin against drug- and starvation-induced gastric erosions in rats.

Sci Pharm. 2013 Jun; 81(2): 549-58
Haider S, Naqvi F, Tabassum S, Saleem S, Batool Z, Sadir S, Rasheed S, Saleem D, Nawaz A, Ahmad S

The present study was designed to investigate the gastroprotective, analgesic, and antipyretic effects of curcumin (Cur), the major constituent of turmeric. Acetylsalicylic acid (ASA) was used in this study as a standard drug for comparison. The analgesic activity was measured using the Hot-Plate Test. The antipyretic and antiulcer effects were assessed using yeast-induced pyrexia and gastric ulceration, respectively. Curcumin (100 mg/kg) injected intra-peritoneally 1 hr prior to the Hot-Plate Test showed significant analgesic activity expressed by both parameters: an increase in latency time and a reduction in paw licking as compared to the controls. In the animal model of pyrexia, curcumin (100 mg/kg injected intra-peritoneally) exhibited a significant reduction in the rectal temperature after 1 hr, 2 hrs, 4 hrs, and 5 hrs of treatment, indicating the antipyretic effect of curcumin. Rats with orally administered curcumin (200 mg/kg) did not show any lesions on the inner lining of the stomach after a 16 hr fast, indicating the gastroprotective effects of curcumin as compared to saline- and acetylsalicylic acid-administered rats. The significantly low ulcer index in curcumin-treated rats following starvation highlights the gastroprotective characteristics of curcumin. HubMed – drug


Combinatorial Effects of Thymoquinone on the Anticancer Activity and Hepatotoxicity of the Prodrug CB 1954.

Sci Pharm. 2013 Jun; 81(2): 519-30
Talib WH, Abukhader MM

One of the major causes of clinical trial termination is the liver toxicity induced by chemotherapeutic agents. Treatment with anticancer drugs like CB 1954 (5-(Aziridin-1-yl)-2,4-dinitrobenzamide) is associated with significant hepatotoxicity. Thymoquinone (TQ), extracted from Nigella sativa, is reported to possess anticancer and hepatoprotective effects. The aims of the present study were to use TQ to reduce hepatotoxicity associated with CB 1954 and to augment its anticancer activity against the resistant mouse mammary gland cell line (66 cl-4-GFP).Balb/C mice were transplanted with the 66cl-4-GFP cell line and in vivo antitumor activity was assessed for CB 1954 (141 mg/kg), TQ (10 mg/kg), and a combination of CB 1954 and TQ. Changes in tumor size and body weight were measured for each treatment. Histological examination of tumors and liver tissue samples was performed using the standard hematoxylin/eosin staining protocol, and serum levels of the liver enzymes AST and ALT were used as biomarkers of hepatotoxicity.Severe liver damage and elevated plasma levels of AST and ALT were observed in the group treated with CB 1954. Treatment of tumor-bearing mice with a combination of CB 1954 and TQ caused a significant regression in tumor size and induced extensive necrosis in these tumors. The combination also protected the liver from drug-induced damage and reduced the plasma levels of AST and ALT to their normal ranges.These results suggest that the use of TQ with CB 1954 can reduce CB 1954-induced hepatotoxicity and enhance its anticancer activity, indicating the potential use of this combination in clinical studies. HubMed – drug


Determination of Cefixime by a Validated Stability-Indicating HPLC Method and Identification of its Related Substances by LC-MS/MS Studies.

Sci Pharm. 2013 Jun; 81(2): 493-503
Talebpour Z, Pourabdollahi H, Rafati H, Abdollahpour A, Bashour Y, Aboul-Enein HY

Cefixime is an important cephalosporin antibiotic that easily decomposes and releases different related substances in preparation and storage steps. The objective of the current study was to develop a simple, precise, and accurate isocratic liquid chromatography (LC) method for the determination of cefixime in the presence of its related substances generated from thermal stress in the bulk drug. The chromatographic conditions were comprised of a reversed-phase C18 column (4.6 × 250 mm, 5 ?m) with a mobile phase composed of water: acetonitrile (85:15 v/v, with 0.5% formic acid) and ultraviolet detection (UV). Some thermal degradation products were identified using a proposed liquid chromatography-mass spectrometry method. Five peaks (A, B, C, D, and E impurities based on British Pharmacopoeia) were known and a few unknown peaks appeared in the thermal stress solution of cefixime. The linear regression analysis data for the calibration plot of the LC-UV method showed a good linear relationship in the concentration range 0.9-1000.0 ?g mL(-1). The recovery of the optimized method was between 94.6 and 98.4% and the inter- and intra-day relative standard deviations were less than 3.3%. The obtained results shown in the LC-UV proposed method can be conveniently used in a quality control laboratory for routine analysis of cefixime for the assay and related substances, as well as for the evaluation of stability samples of bulk drugs. HubMed – drug


Complexity in estimation of esomeprazole and its related impurities’ stability in various stress conditions in low-dose aspirin and esomeprazole magnesium capsules.

Sci Pharm. 2013 Jun; 81(2): 475-92
Reddy PS, Hotha KK, Sait S

A complex, sensitive, and precise high-performance liquid chromatographic method for the profiling of impurities of esomeprazole in low-dose aspirin and esomeprazole capsules has been developed, validated, and used for the determination of impurities in pharmaceutical products. Esomeprazole and its related impurities’ development in the presence of aspirin was traditionally difficult due to aspirin’s sensitivity to basic conditions and esomeprazole’s sensitivity to acidic conditions. When aspirin is under basic, humid, and extreme temperature conditions, it produces salicylic acid and acetic acid moieties. These two byproducts create an acidic environment for the esomeprazole. Due to the volatility and migration phenomenon of the produced acetic acid and salicylic acid from aspirin in the capsule dosage form, esomeprazole’s purity, stability, and quantification are affected. The objective of the present research work was to develop a gradient reversed-phase liquid chromatographic method to separate all the degradation products and process-related impurities from the main peak. The impurities were well-separated on a RP8 column (150 mm × 4.6mm, X-terra, RP8, 3.5?m) by the gradient program using a glycine buffer (0.08 M, pH adjusted to 9.0 with 50% NaOH), acetonitrile, and methanol at a flow rate of 1.0 mL min(-1) with detection wavelength at 305 nm and column temperature at 30°C. The developed method was found to be specific, precise, linear, accurate, rugged, and robust. LOQ values for all of the known impurities were below reporting thresholds. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation in the presence of aspirin. The developed RP-HPLC method was validated according to the present ICH guidelines for specificity, linearity, accuracy, precision, limit of detection, limit of quantification, ruggedness, and robustness. HubMed – drug