Chloroquine-induced pruritus remains one of the most common side-effects in the use of chloroquine in the prophylaxis and treatment of uncomplicated malaria before the advent of artemisinin-based combination therapies. It has been reported to vary from a tolerable to intolerable intensity among susceptible individuals resulting in disruption of treatment and development of resistance to the drug thus leading to therapeutic failures as reported. This scourge is quite challenging due to the complex physiologic mechanism that has not been fully elucidated. Factors observed to be responsible in the induction of pruritus such as age, race, heredity, density of parasitaemia; impurities in formulations, plasmodial specie, dosage form and metabolites have been discussed in this review. Efforts to ameliorate this burden have necessitated the use of drugs of diverse pharmacological classes such as antihistamines, corticosteroids and multivitamins either alone or as a combination. This review is to look into the use of chloroquine retrospectively, and consider its re-introduction due to its safety. Efficacy can be attained if the pruritic effect is resolved.

Cyclin-dependent kinases are most extensively studied targets for cancer chemotherapy since the tumor cells exhibit false checkpoints and can proliferate even if the genome is compromised. Cyclin-dependent kinases ensure the tight regulation of the cell cycle execution by mediating phosphorylation of cellular proteins. Deregulation of the cyclin-dependent kinase 2 activity by cellular and external factors leads to many diseases like cancers. Different methods like radiolabeled, fluorescence and luminescence are available for screening of library of compounds against kinases. However, bioluminescent methods offer several advantages like low background and no effect of fluorescent compound interference. Present study is focused on development, optimization and validation of cyclin-dependent kinase 2 assay which is suitable for identification potent and selective, ATP competitive and non-competitive inhibitors of cyclin-dependent kinase 2. The aim of present investigation was to optimize the assay for cyclin-dependent kinase 2/cylin A and cyclin-dependent kinase 2/cyclin E with use of bioluminescence based biochemical reaction. Both cyclin-dependent kinase 2 which are cyclin-dependent kinase 2/cyclin A and cyclin-dependent kinase 2/cyclin E complexes, have different affinity for ATP. Therefore, both isoform analogs of cyclin-dependent kinase 2 were optimized separately. Optimum cyclin-dependent kinase 2/cyclin A and cyclin-dependent kinase 2/cyclin E concentration were found to be 250 ng/well and 200 ng/well, respectively. Optimum substrate (histone H1) concentration was found to be 2.5 mg/ml for both cyclin-dependent kinase 2 analogs. Optimum reaction time was found to be 20 min for both cyclin-dependent kinase 2/cyclin complexes.

The microcrystalline cellulose is an important ingredient in pharmaceutical, food, cosmetic and other industries. In this study, the microcrystalline cellulose, obtained from the stalk of Sorghum caudatum was evaluated for its physical and tableting characteristics with a view to assessing its usefulness in pharmaceutical tableting. The microcrystalline cellulose, obtained from the stalk of Sorghum caudatum, obtained by sodium hydroxide delignification followed by sodium hypochlorite bleaching and acid hydrolysis was examined for its physicochemical and tableting properties in comparison with those of the well-known commercial microcrystalline cellulose grade, Avicel PH 101. The extraction yield of this microcrystalline cellulose, obtained from the stalk of Sorghum caudatum was approximately 19%. The cellulose material was composed of irregularly shaped fibrous cellulose particles and had a moisture content of 6.2% and total ash of 0.28%. The true density was 1.46. The flow indices showed that the microcrystalline cellulose, obtained from the stalk of Sorghum caudatum flowed poorly. The hydration, swelling and moisture sorption capacities were 3.9, 85 and 24%, respectively. Tablets resulting from these cellulose materials were found to be without surface defects, sufficiently hard and having disintegration time within 15 min. The study revealed that the microcrystalline cellulose, obtained from the stalk of Sorghum caudatum compares favourably with Avicel PH 101 and conformed to official requirement specified in the British Pharmacopoeia 1993 for microcrystalline cellulose.

A selective and sensitive liquid chromatographic method has been developed for simultaneous determination of zonisamide and its four related substances in pharmaceutical dosage forms. The assay involved an isocratic elution in perfectsil Target C18 column using a mobile phase composition of disodium hydrogen phosphate buffer, acetonitrile and methanol (650:150:200 v/v, pH adjusted to 3±0.05) with flow rate 1.2 ml/min and analyte monitored at 240 nm. Also a simple and precise spectrophotometric method was developed for dissolution studies. These proposed methods are sensitive, accurate, reproducible and useful for the routine determination of zonisamide in pharmacy.

A rapid, sensitive and specific reversed-phase high performance liquid chromatographic method with diode-array detection has been developed and validated for the determination of hydroxybenzene (0.494%, w/w) in a commercially available cream pharmaceutical formulation. Isocratic chromatography was performed on a C18 column with methanol-water 60:40 (v/v) containing 0.1% phosphoric acid (v/v) as mobile phase at a flow rate of 1.0 ml/min. UV detection was at 254 nm. Linearity of the method was excellent (r ² = 0.9999). The relative standard deviation values for intra- and inter-day precision studies were < 1% and the recovery of hydroxybenzene was >99%. The limit of detection and quantitation for hydroxybenzene was found to be 13.5 η g/ml and 2 μg/ml, respectively. The method was also validated for specificity and robustness. The method was found to be robust and can be reliably used to determine the hydroxybenzene content of marketed formulations.

A new and simple reversed-phase liquid chromatographic method has been developed and validated for the determination of 2-phenoxyethanol preservative (0.3%, w/w) in senselle lubricant formulation. The separation was achieved with acetonitrile-tetrahydrofuran-water (21:13:66, v/v/v) as mobile phase, a C ₈ column, and UV detection at 258 nm. The calibration curve is linear (r ² = 0.9999) from 20-140% of the analytical concentration of 0.75 mg/ml. The mean percent relative standard deviation values for intra- and inter-day precision studies are <1%. The recovery of 2-phenoxyethanol ranged between 99.76 and 100.03% from lubricant formulation. The limits of detection and quantitation are determined to be 0.094 and 0.15 mg/ml, respectively. The method was found to be robust and can be successfully and reliably used to determine the 2-phenoxyethanol preservative content of marketed formulations.

Fexofenadine is a selective histamine H ₁ receptor antagonist, used for relief of the symptoms of allergy. However its aqueous solubility is very poor. Solid inclusion complexes of fexofenadine and β-cyclodextrin were prepared at the molar ratios of 1:1 and 1:2 by kneading, and coprecipitation methods to improve its solubility. Characterization of the complexes was performed using infrared spectroscopy, X-ray diffractometry, and in vitro dissolution studies. Fexofenadine was found to exhibit interaction with β-cyclodextrin both in solid and liquid state. Phase solubility studies indicated that fexofenadine forms a stable complex with β-cyclodextrin. Both IR spectroscopy and X-ray diffractometry studies indicated interaction of fexofenadine with β-cyclodextrin. Kneading method at 1:1 and co-precipitation method at 1:1 and 1:2 molar ratios showed significant interaction. In vitro dissolution studies confirmed the same results.

A molecular docking study was carried out on 28 compounds belonging to 2,4-diaminoquinazoline and 2,4-diaminopteridine analogs using Glide, FlexX and GOLD programs and the X-ray crystallographic structures of the quadruple mutant (1J3K:pdb) and wild type (1J3I:pdb) Plasmodium falciparum dihydrofolate reductase enzyme. The experimental conformation the bound ligand WR99210 was precisely reproduced by the docking procedures as demonstrated by low (<2.00 Ε) root-mean-square deviations. The results indicated that most of the compounds dock into the active sites of both the wild type and quadruple mutant P. falciparum dihydrofolate reductase enzymes. Visual inspection of the binding modes also demonstrated that most of the compounds could form H-bond interactions with the key amino acid residues (Asp54, Ile14 and Leu/Ile164) and with better docking scores than the bound compound (5). Their long side chains orient in the hydrophobic portion of the active site which is occupied by trichloro aryloxy side chain of WR99210 (5). Thus, avoid potential steric clashes with Asn108 (mutated from Ser108). Such a clash is known to be responsible for the resistance of the P. falciparum to pyrimethamine and cycloguanil.

The effects of the methanol extract of the stem bark of Prosopis africana (Guill., Perrott. and Rich.) Taubert (Fabaceae) on bleeding/clotting and coagulation time, excision and dead space wounds were studied in rats. Also, the extract was subjected to antibacterial, and acute toxicity and lethality (LD ₅₀ ) tests. The extract significantly (P<0.05) reduced bleeding/clotting and coagulation time in rats. It also reduced epithelialization period of excision wounds in rats and inhibited the growth of laboratory strains of Staphylococcus aureus, Bacillus subtilis, Salmonella typhi, Pseudomonas aeruginosa and Klebsiella pneumoniae to varying extents. Acute toxicity and lethality (LD ₅₀ ) test on the extract established an LD ₅₀ of 774 mg/kg (i.p) in mice while phytochemical analysis gave positive reactions for alkaloids, saponins, tannins, flavonoids, steroids, terpenoids and carbohydrates. The results of this study demonstrate the beneficial effects of the stem bark of P. africana in wound care.

Urinary stones are one of the oldest and the most common afflictions in humans. This disease has tormented humans since the earliest records of civilization. Ten percent of men and 3 % of women have a stone during their adult lives. Calcium containing stones are the most common comprising about 75 % of all urinary calculi, which may be in the form of pure calcium oxalate (50 %) or calcium phosphate (5 %) or a mixture of both (45 %). A number of plants have been mentioned in the Indian ayurvedic system, which plays a vital role in the inhibition of kidney stones. In the present study, the inhibitory potency of crude extracts or fractions of successive solvent extractions of Terminalia arjuna bark was evaluated on various stages of formation of calcium phosphate and on the growth of calcium oxalate monohydrate crystals in vitro. Results obtained indicated that Terminalia arjuna bark has the potential to inhibit the formation of both calcium phosphate and calcium oxalate crystals in vitro. Butanol fraction of Terminalia arjuna extract was the most effective in inhibiting formation of calcium phosphate and calcium oxalate crystals in vitro.

The objective of the present study was to prepare and characterize in vitro and in vivo performance of a sustained release microsphere formulation of 4-chlorocurcumin, a novel curcumin analogue. A spray dried technique with ethylcellulose as the polymer was used in the preparation of these microspheres. Microspheres were characterized for drug content, particle size and shape, in vitro drug release and the drug-polymer interaction. To assess in vivo performance, both pharmacokinetics and hepatoprotective activity were investigated. Results were compared with an equivalent i.v. solution. The microspheres of 4-chlorocurcumin with ethylcellulose were successfully prepared using a spray-dried technique. These microspheres were able to sustain the release of the drug both in vitro as well as in vivo. Microspheres offered better pharmacokinetic and hepatoprotective properties to the drug compared to its solution form.

The extracts of Anacardium occidentale have been used in the management of different cardiovascular disorders in Nigeria. These have necessitated the assessment of the toxicity of this plant extract in sub-chronic administration. The inner stem bark of Anacardium occidentale was extracted with 80 % methanol and quantitatively analysed for antinutrients and some heavy metals. The phytochemical compositions and acute toxicity of the extract were determined also. Toxicity profiles of the extract on some liver function parameters were evaluated following a sub-chronic oral administration at doses of 1.44 and 2.87 g/kg. The phytochemical screening of extract revealed the presence of high amount of tannins, moderate saponins and trace of free reducing sugars. The antinutrient levels were 5.75 % (tannins), 2.50 % (oxalates), 2.00 % (saponins), 0.25 % (phytate) and 0.03 % (cyanide). The quantity of iron detected from dried crude was 8.92 mg/100 g, while lead and cadmium were non-detectable. The extract had LD ₅₀ of 2.154 g/kg p.o. in mice. Sub-chronic administration of the extract significantly increased the serum levels of alanine aminotransaminase and aspartate aminotransaminase, which are indicative of liver damage. The serum levels of alkaline phosphatase and total protein of the treated animals were not significantly increased. The effects of sub-chronically administered extract on hepatocytes were minimal as the serum alkaline phosphatase; total bilirubin and total protein levels in treated animals were not significant (p< 0.05). Thus, sub-chronic administrations of Anacardium occidentale inner stem bark extract did not significantly (p< 0.05) depress the function of hepatocytes in Wistar rats.

A series of new 3-(4-methylcoumarinyl-7-oxymethyl)-6-substitutedphenyl-5,6-dihydro-s-triazolo (3,4-b)(1,3,4)-thiadiazoles 2(a-j) have been synthesized by reacting 5-(4-methyl coumarinyl-7-oxymethyl)-4-amino-3-mercapto(4H)-1,2,4-triazole with various aromatic aldehydes by microwave assisted organic synthesis. The structure of the compounds 2 (a-j) has been confirmed by IR, ¹ H NMR and mass spectral data. All the compounds were screened for antimicrobial and antioxidant activity. Among the compounds tested, compounds 2d (4-dimethyl amino phenyl derivative) and 2h (3,4-dimethoxy phenyl derivative) showed better antimicrobial and antioxidant activity than rest of the compounds in the series.

A new process impurity was detected during the HPLC analysis of Tizanidine hydrochloride (I) batches. The impurity (II) was isolated by preparative HPLC and characterized by NMR and Mass spectral analysis as 5-S-ethyl-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine hydrochloride.

In the present study, a series of 4-(4-substituted aryl) semicarbazones were synthesized from substituted anilines and subsequently evaluated for their anticonvulsant activities. The anticonvulsant activities were established by the anticonvulsant drug development (ADD) programme NIH, USA using experimental animal, adult male FCM mice (20-25 g) and adult Sprague-Dawley rats (100-150 g) and screened against electroshock seizure, subcutaneous metrazole and minimal neurotoxicity tests in mice. Compound 7 was found equipotent to carbamazepine in both MES and ScPTZ tests. This study has highlighted the importance of distal alkyl chain which influences the anticonvulsant activity.

The present study was designed to compare ulcer protective effect of proton pump inhibitors viz. omeprazole, rabeprazole and lansoprazole against dexamethasone plus pylorus ligation induced ulcer model. Dexamethasone (5 mg/kg) was used as an ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all the rats 15 min after the pylorus ligation. Omeprazole (20 mg/kg), rabeprazole (20 mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 min prior to ligation was used for ulcer protective studies, gastric secretion and mucosal studies. Effects of proton pump inhibitors were determined by the evaluation of various biochemical parameters such as ulcer index, free and total acidity, gastric pH, mucin, pepsin and total proteins. Oral administration of proton pump inhibitors showed significant reduction in gastric acid secretion and ulcer protective activity against dexamethasone plus pylorus ligation induced ulcer model. The % protection of omeprazole, rabeprazole and lansoprazole was 84.04, 89.36 and 79.78, respectively. Rabeprazole significantly inhibited the acid-pepsin secretion and increased the gastric mucin secretion. The observations made in the present study suggest that rabeprazole is the most effective gastric antisecretory and ulcer healing agent as compared to omeprazole and lansoprazole.

In the present study, the effect of essential oil of the root of Angelica archangelica Linn. was evaluated against electrically and chemically induced seizures. The seizures were induced in mice by maximal electroshock and pentylenetetrazol. The effect of essential oil of the root of Angelica archangelica on seizures was compared with standard anticonvulsant agents, phenytoin and diazepam. The essential oil of the root of Angelica archangelica suppressed duration of tonic convulsions and showed recovery in maximal electroshock induced seizures while it delayed time of onset of clonic convulsions and showed mortality protection in pentylenetetrazol induced seizures. The essential oil of the root of Angelica archangelica also produced motor impairment at the antiseizure doses. The study indicated that the essential oil exhibited antiseizure effect. The antiseizure effect may be attributed to the presence of terpenes in the essential oil.

Schiff bases (9a-l) of 3-amino-6,8-dibromo-2-phenyl-quinazolin-4-(3H)-ones (8) with various substituted aldehydes were obtained by refluxing 1:1 molar equivalents of the reactants in dry ethanol for 6 h. The aminoquinazoline (8) was inturn obtained from 3,5-dibromoantharlinic acid via intermediate (7). All the synthesized compounds (9a-l) were evaluated for their anticonvulsant activity on albino mice by maximal electroshock method using phenytoin as a standard. The compound (9l) bearing a cinnamyl function displays a very high activity (82.74 %) at dose level of 100 mg/kg b.w.

Rapid and efficient methods for the synthesis of an important intermediate of benazepril ethyl 3-phthalimido-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one-1-acetate under the influence of microwave irradiation are described. A comparative study of conventional and microwave assisted method is briefly discussed.

A simple, precise and accurate HPLC method has been developed and validated for assay of lercanidipine hydrochloride in tablets and for determination of content uniformity. An isocratic separation was achieved using a Chromasil YMC Pack C ₈ , 150 Χ 4.6 mm i.d., 5μm particle size columns with a flow rate of 1 ml/min and using a UV detector to monitor the elute at 240 nm. The mobile phase consisted of 0.02 M ammonium dihydrogen phosphate buffer:methanol (35:65, v/v) with pH 3.5 adjusted with phosphoric acid. The method was validated for specificity, linearity, pre­cision, accuracy, robustness and solution stability. The specificity of the method was deter­mined by assessing interference from the placebo and by stress testing of the drug (forced degradation). The method was linear over the concentration range of 20-80 μg/ml (r ² = 0.9992) with a limit of detection and quantitation of 0.1 and 0.3 μg/ml respectively. Intraday and interday system and method precision were determined and accuracy was between 99.3-101.9 %. The method was found to be robust and suitable for assay of lercanidipine hydrochloride in a tablet formulation and for determination of content uniformity. Degradation products resulting from the stress studies did not interfere with the detection of lercanidipine hydrochloride and the assay is thus stability-indicating.

A new reverse phase high performance liquid chromatography method for the simultaneous estimation of frusemide and amiloride hydrochloride in tablet formulation is developed. The determination was carried out on a HIQ SIL, C18 (250Χ4.6 mm, 5 μm) column using a mobile phase of 50 mM phosphate buffer solution:acetonitrile (50:50 v/v, pH 3.0). The flow rate was 1.0 ml/min with detection at 283 nm. The retention time for frusemide was 3.038 min and for amiloride hydrochloride 10.002 min. Frusemide and amiloride hydrochloride showed a linear response in the concentration range of 20-200 μg/ml and 10-100 μg/ml, respectively. The results of analysis have been validated statistically and by recovery studies. The mean recoveries found for frusemide was 99.98% and for amiloride hydrochloride was 100.09%. Developed method was found to be simple, accurate, precise and selective for simultaneous estimation of frusemide and amiloride hydrochloride in tablets.

Organic extracts (ethanol, petroleum ether and chloroform) of two medicinal plants Lawsonia inermis L. and Mimosa pudica L. were proven for antibacterial properties against 15 Gram-positive and Gram-negative human pathogenic bacteria. Among the three types of extracts tested, ethanol extract was found to possess maximum antibacterial activity. The diameter of the zone of inhibition of bacterial growth showed that Gram-negative bacteria are more sensitive than Gram-positive bacteria to plant extracts. Between the two plants species studied, Lawsonia inermis extract showed more antibacterial activity compared to Mimosa pudica extract.

The aim of the present study was to explore the hepatoprotective activity of the ethanol extract of leaves of Gymnosporia montana (Roth) Bemth. (Family: Celastraceous) against paracetamol-induced hepatotoxicity. Hepatotoxicity in Wistar rats was induced by a single intraperitoneal dose of 500 mg/kg of paracetamol and studied by comparing parameters such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase and histopathological examination of liver. Pre and post-treatment with ethanol extract of Gymnosporia montana (Roth) Bemth. at doses of 50 and 100 mg/kg was studied by comparing the above mentioned parameters with silymarin (100 mg/kg) as standard. Both doses of ethanol extract of Gymnosporia montana (Roth) Bemth. were found to be hepatoprotective. Extract at the dose of 100 mg/kg produced effects comparable to those of silymarin. The present study indicates that alcohol extract of Gymnosporia montana (Roth) Bemth. possessed significant hepatoprotective activity.

Extracts of Aloe vera whole plant, Eucalyptus globulus leaves, Ficus infectoria bark, Ficus religiosa bark and Piper betel leaves were studied for antibacterial activity on resistant and sensitive strains, isolated from skin and soft tissue infections. A combination of hot alcoholic extracts of Ficus infectoria, Ficus religiosa and Piper betel were found to be more effective against all the isolates. The combined extract was formulated in different ointment bases such as polyethylene glycol, gelatin, sodium alginate, carbopol, cream base and honey. These were then evaluated to find a suitable base for preparation of an ointment. In vitro study of the release of antimicrobials and kill-time studies of the herbal ointments was carried out against multi-drug resistant isolate of Pseudomonas. The ointment showed bactericidal activity within 2 h against the resistant strain of Pseudomonas spp.

A forced degradation study on roflumilast drug substance was conducted under the conditions of hydrolysis, oxidation, thermal and photolysis. The method was developed and optimized by analyzing forcefully degraded samples. The best separation was achieved on a Zorbax SB C18 1.8 ΅m column with 0.005 M ammonium formate buffer pH 3.5 and acetonitrile as mobile phase in a 13 min run time. The proposed method was able to resolve all the possible degradation products formed during stress study. The drug was stable to neutral, thermal and photolytic conditions but unstable to acidic, alkaline and oxidative conditions at 80Ί for 24 h. The degradation products resulting from stress study did not interfere in assay and related substances of roflumilast and thus the method can be regarded as stability indicating. An alternate method was also developed on a conventional 250Χ4.6 mm, 5 ΅m column wherein runtime was 38 min. Thus rapid resolution high throughput column was able to reduce the run time from 38 min to 13 min.

A prescription audit was carried out among the outpatient attendees of 31 secondary level hospitals under Maharashtra Health Systems Development Project. Use of drugs and cost of treatment of diarrhoea were studied using the prescriptions for diarrhoea collected for the prescription audit. Average number of drugs prescribed per prescription for treatment of diarrhoea was 3.7. It was higher than average number of drugs per prescription in the Maharashtra Health Systems Development Project hospitals in general. About three fourths of the prescriptions contained oral rehydration salts. Furazolidone and metronidazole were prescribed in about half of the prescriptions. Cotrimoxazole was prescribed in about one fourth of prescriptions. About 60% of the prescriptions contained other drugs. The average cost of prescription for diarrhoea was Rs. 14 and increased with the number of drugs prescribed. Average cost of prescription was the highest for those written by general practitioners. Pathological tests were indicated only in case of 11%.