International Journal of Pharmaceutical Sciences and Drug Research

08-12

Authors: R. K. Maheshwari*, S. Jawade, A. Fouzdar

Furosemide is a high ceiling diuretic that exhibits antihypertensive activity and also used in treatment of edema associated with congestive heart failure, liver cirrhosis, renal disease, including nephrotic syndrome. It is practically insoluble in water. The effect of hydrotropes such as urea, sodium citrate, sodium benzoate, sodium acetate and blends on the solubility of furosemide was investigated. The enhancement in the solubility of furosemide was up to 200.46 fold in 40% sodium benzoate solution, 14.81 fold in 40% urea solution, 11.85 fold in 40% sodium citrate solution and 9.35 fold in 40% sodium acetate solution compared to its solubility in distilled water. The solubility of drug was raised up to 357.87 fold in blend BUC (containing sodium benzoate, urea and sodium citrate in the ratio of 13.3:13.3:13.3) which was about 1.35 times more than the solubility in the blend BU (containing sodium benzoate and urea in the ratio of 20:20). This proved a synergistic enhancement in solubility of a poorly water soluble drug due to mixed hydrotropy. Combination of hydrotropic agents giving synergistic solvent action can minimize the amount of hydrotropic agents employed, minimizing the chances of their individual toxicities. Aqueous injection of furosemide, using the mixed hydrotropic solubilization technique, was developed. The developed formulation was studied for physical and chemical stability. The prepared formulation was unaffected in respect of color stability. There was no color change or precipitate was found in the developed formulation. In the freeze thaw study there was no precipitation and no turbidity in the developed parenteral formulation at the end of the testing. Chemical stability showed that there was no appreciable loss of furosemide in the formulation stored for 30 days at different temperatures. So it can be assumed that the formulation will have sufficient chemical stability at room temperature.

22-26

Authors: Roopkishora1, Amit Singh2, Chhote Lal Singh2*

The objective of present study was to formulate and characterize the nanoparticles of hydroxyl chloroquine sulphate (HCQ). Nanoparticles were prepared by the w/o/w emulsion - solvent evaporation method using polymer Eudragit® RL-100, acetone, and surfactant poloxmer-188 solutions. Amount of polymer, organic solvent and surfactant was selected as formulation variable. Characterization of the nanoparticles was performed by measuring particle size, zeta potential, surface morphology, interactions, drug entrapment efficiency, in-vitro drug release, % yield and stability. The formulated nanoparticles were found to be spherical and uniform in particle size with less than one poly dispersity index. The zeta potential of nanoparticles was found -34 (mv) represent higher stability of colloidal dispersion. In another set of characterization the percentage yield and entrapment was found to be in the range of 55-68% and 63.14% respectively. The in-vitro release shows 87.93% at its maximum level in 24 hours of study. The suspension of formulation was found more stable in refrigerated environment. The release kinetics evaluation revealed the drug release was following Higuchi model, which ensures the possibility of long term release profile from the nanoparticles formulation so that its concentration maintained within therapeutic level for larger period of time so that safe and efficacious for malarial and rheumatoid patients.

33-39

Authors: Shiva Shanker Rai1*, Atanu Banik2, Ankit Singh2, Meenu Singh2

The objective of the present study was to evaluate antiulcer potential of aqueous and ethanolic extract Clitoria ternatea in different experimental induced ulcer models in rats. In the present study different extracts [ethanolic (200 mg/kg and 400 mg/kg) and aqueous (200 mg/kg and 400 mg/kg) extract of whole plant were examined in Pylorus ligation and Indomethacin induced gastric ulcer in rats. Various parameters like volume of gastric acid secretion, pH, total acidity, ulcer index and antioxidant parameters were determined and compared between extract treated, standard and vehicle control group animals following ulcer induction. Among different dose of alcoholic extract, high dose showed significant antiulcer activity in Pylorus ligation and Indomethacin induced ulceration. The result of present study concluded that the alcoholic extract of whole plant of Clitoria ternatea has antiulcer activity in Pylorus ligation and Indomethacin induced gastric ulcer model in rats. The extract containing flavonoids show antiulcer activity, indicating the flavonoids component of the extract to be responsible for the activity of the extracts.

46-51

Authors: Renu Kadian*, Milind Parle

The present study was undertaken to evaluate the antipsychotic potential of Ocimum sanctum in experimental animal models. Male Wistar rats (180-220 g) and albino mice (25-30 g) were used for the study. The antipsychotic effect of the Ocimum sanctum was evaluated on haloperidol induced catalepsy, cooks pole climbing apparatus, locomotor activity on actophotometer, ketamine induced stereotype behavior. Different groups of rats were fed orally with a specially prepared diet containing various concentrations (2% w/w, 4% w/w and 8% w/w) of Ocimum sanctum leaves paste (OCLP) for 15 consecutive days. Further, the biochemical estimations were done by estimating brain dopamine levels. The OCLP produced significant dose dependent potentiation of haloperidol (1mg/kg, i.p.) induced catalepsy in rats, significantly increased the time taken by the rat to climb the pole in dose dependent manner, significantly decreased the locomotor activity. The OCLP significantly decreased ketamine (50 mg/kg, i.p.) induced stereotyped behavior in a dose dependent manner. Ocimum sanctum leaves paste (OCLP) significantly decreased the brain dopamine levels. The results suggest that OCLP posse’s antipsychotic activity. Further neurochemical investigation can explore the mechanism of action of the plant drug with respect to anti-dopaminergic functions and help to establish the plant as an antipsychotic agent.

59-62

Authors: C. C. Ekwealor*, C. A. Oyeka

The present study was carried out to investigate the in vitro anti dermatophyte activities of crude methanol and aqueous extracts of Lawsonia inermis leaves. The anti dermatophyte activities was tested against Microsporum audouinii, Microsporum ferrugineum, Trichophyton megninii, Trichophyton tonsurans and Trichophyton rubrum, recovered from rice farmers with fungal skin infections in Anambra State, Nigeria. From the result obtained, growth of dermatophytes was inhibited at the varied concentrations of crude methanol extract with the diameter zone of inhibition increasing with the increase in concentration. At the lowest concentration of 10 mg/disc, diameter zone of inhibition range of 8.0 mm-16.8 mm was recorded against the different dermatophytes. At 80 mg/disc, T. rubrum showed the highest diameter zone of inhibition (18.8 mm), followed by M. audouinii (18.0 mm) while T. megninii was the least inhibited (12.0 mm). Water extract of L. inermis also inhibited all the test dermatophyte. M. audouinii was the most susceptible with diameter inhibition zone of 14.5 mm. Minimum inhibitory concentration was recorded at 25 mg/ml for all dermatophytes while fungicidal action was recorded at concentrations of 50 mg/ml for M. audouinii and T. rubrum, 100 mg/ml for M. ferrugineum and 200 mg/ml for T. megninii and T. tonsurans. These results demonstrated that L. inermis has anti dermatophyte activities and could be a good source for the production of plant based antifungal drugs.

68-72

Authors: T. Saldanha, D. Kaspate*, B. Karmarkar, K. Shah, S. Narkhede

The aim of the present study was to investigate the antidepressant activity of Momordica charantia in swiss albino mice. In this study ethanolic extract of unripen fruit along with seeds of this plant was investigated by using animal models like Despair Swim Test (DST) and Tail Suspension Test (TST) along with 100, 300 and 500 mg/kg (p.o.) doses and distilled water as a vehicle for 14 days of treatment and imipramine as a standard drug was administered orally on the test days. During dosing period test was carried out on 1st, 7th and 14th day of treatment. The results showed a significant decrease in immobility time of treated mice as compared to control group.

78-82

Authors: Lasha Mskhiladze1*, David Chincharadze1, Monique Tits2, Jean-Noël Wauters2, Akeila Bellahcène3, Vincent Castronovo3, Ange Mouithys-Mickalad4, Thierry Franck4, Michel Frédérich2

The present study evaluates the in vitro anticancer, antiplasmodial and antioxidant activity of the ethanolic crude extract from the flowers of Allium gramineum growing in Georgia and of one flavonol and two steroidal glycosides which were isolated from this plant. The flowers were extracted with ethanol and this total extract was subjected to successive bioguided fractionations to provide glycosides 1-3. Their structures were elucidated on the basis of NMR and ESI-MS spectrometric data in comparison with the existing literature and have been identified as: isorhamnetin-3-O-β-D-glucopyranoside (1), diosgenin-3-O-α-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (Prosapogenin A of dioscin) (2), diosgenin-3-O-α-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)-]-β-D-glucopyranoside (Deltonine) (3). The ethanolic extract has been shown to strongly inhibit the growth of breast adenocarcinoma cell lines, with an IC50 of 4.5 ± 0.7μg/mL for MDAMB-231 and 4.8 ± 0.9μg/mL for MCF-7 cells. The cytotoxic activity was related to 2 and 3 which exhibited potent cytotoxicity, with an IC50 of ± 3μM. Concerning antiplasmodial activities, only weak activities were observed using the ethanolic extract and the two saponins. The flavonoid was almost inactive. Finally, the radical-scavenging activity of the ethanolic extract was tested in presence of ABTS•+ solution. A decrease of the absorbance intensity was observed, with an IC50 value of 22.1 ± 0.6μg/mLwhile trolox, used as Standard drug, showed a pronounced activity (IC50 = 12.7±0.5μM). The glycoside 1 showed the lowest IC50 value of 20.1 ± 0.8μM while both 2 and 3 exhibited very weak radical scavenging activity.

89-95

Authors: Pankaj Patil, Sanjay Nipanikar, Hanumant Bhusnar, Dheeraj Nagore*

Simple, accurate, precise, sensitive and validated HPLC method was developed for simultaneous determination of Guggulsterone E (GE), Guggulsterone Z (GZ), 11-keto-β-boswellic acid (KBA), 3- Acetyl 11-keto-β-boswellic acid (AKBA), Withaferin A (WA) and 6-Gingerol (GNRL) in Ariflex tablet. The gradient RP-HPLC analysis was performed on Inertsil ODS-3V C18 column (250 × 4.6 mm id), using a mobile phase consisting of 0.1% Ortho-phosphoric acid and mixture of acetonitrile: Methanol (50: 50 v/v) in solvent gradient elution for 60 min at a flow rate of 1.0 mL min−1. Quantification was carried out using a photodiode array detector at 225nm. The employment of diode array detector allowed selectivity confirmation by peak purity evaluation. The method was validated according to International Conference on Harmonization guidelines. No chromatographic interference from tablet excipients was found and hence this method is applicable for simultaneous determination of GE, GZ, KBA, AKBA, WA and GNRL in Ariflex Tablet.

100-104

Authors: Sharath Chandra Sollepura Purushothama1, Sharada Angatahally Chandrashekaraiah2*

The atypical antipsychotic drugs used in recent times for the treatment of chronic or acute psychotic (CNS) disorders, are found to cause Extrapyramidal side effects (EPS). Earlier studies have revealed that an enhanced oxidative stress accompanied with high glutamate transmission lead to extrapyramidal symptoms, thus limiting the use of established antipsychotic drugs. Therefore the current study investigates the effects of 6-fluoro-3-(piperidin-4-yl) benzo[d]isoxazole derivatives designated as S1, S2, S3, S4 as potent antipsychotics and to prove their efficacy in producing menial Extrapyramidal symptoms, by conducting biochemical, neurochemical and behavioural analysis. The behavioural studies on mice showed that chronic administration of standard antipsychotic drugs haloperidol (1 mg/kg i.p) and resperidone (1 mg/kg i.p) to animals have remarkably increased the vacuous chewing movements (VCM`s), VCM`s was noticeably inhibited in test compounds S2 and S3 (1 mg/kg i.p). Neurochemical analysis showed an increase in the concentrations of GABA, dopamine, and norepinephrine in the mice treated with synthesized molecules (S1-S4) compared to standard drugs. Alterations in the enzyme/protein levels of GSH, SOD, catalase and lipid peroxidation have further substantiated the role of free radicals as the underlying cause of EPS. Altogether it can be concluded that the study of synthetic molecules may yield a promising antipsychotic drug which can minimise EPS.

110-115

Authors: Usha Rani N*, Satya Priya B, Nagoor Ankani

A simple, specific and precise high performance liquid chromatographic method was developed and validated for Nebivolol HCl and Amlodipine besylate in a combined tablet dosage form. Nebivolol hydrochloride, a long acting, cardioselective β-blocker and Amlodipine besylate, a calcium channel blocker are considered in combination for the treatment of hypertension. The chromatographic separation was performed using Eclipse XDB plus C18 Column (4.6 × 150 mm, 5μm particle size). The mobile phase consisted of combination of 0.01 M Ammonium acetate buffer (pH 4.5) and Acetonitrile in the ratio of 50:50 v/v at a flow rate of 0.8 ml/min with the detection wavelength at 265 nm. Both the drugs showed good linearity in the concentration range of 10-50μg/ml and 5-25μg/ml respectively with a correlation coefficient of 0.999 for both drugs. The retention time for Nebivolol HCl and Amlodipine besylate were found to be 3.553 and 2.970 min respectively. The developed analytical method was validated for linearity, precision, accuracy, ruggedness, robustness, specificity and system suitability, which were within the acceptance limits according to ICH guidelines. The developed method can successfully be employed for routine quality control of Nebivolol HCl and Amlodipine besylate in combined tablet dosage forms.

120-122

Authors: Vipin Kumar Agrawal1*, Shashank Chaturvedi1, Amresh Gupta2

Albendazole is a class II drug in biopharmaceutical classification system, so its dissolution study is very difficult because of its low solubility and difficulty during estimation of drug in bulk. The present study deals with UV spectrophotometric method development and validation for estimation of albendazole in bulk form. Albendazole is a benzimidazole derivative with an oral broad spectrum of activity against human and animal helminthes parasites. The drug obeyed the Beer’s law and showed good correlation. It showed absorption maxima at 229nm in 0.1 N HCL with 0.05% sodium lauryl sulphate (SLS). The linearity was observed between 4-20μg/ml. The method was applied for the analysis of the drug in the pure, tablet and suspension forms. The slope and intercept of the equation of the regression line are 0.009 and 0.017 respectively. Correlation coefficient was found to be 0.9996. The results of analysis were validated by recovery studies. The recovery was more than 97%. The method was found to be simple, reliable, rapid, precise, specific and reproducible and can be applied for routine analysis of albendazole in different dosage form and dissolution studies.

126-128

Authors: Takayuki Sakurai1*, Ken Iesato1, Seiichiro Sakao1, Kengo Saito2, Koichiro Tatsumi1, Hiroshi Shirasawa2

Lysozyme hydrochloride, derived from Hen Egg Lysozyme, is one of classical anti-airway inflammatory drugs. It has been widely administered in Japan, but its molecular potential is unknown. To confirm this classical drug as anti-inflammatory agent, pro-inflammatory cytokines in Epithelial Cells infected by RSV with lysozyme hydrochloride were measured. Lysozyme hydrochloride suppressed the production of IL-6, IL-1β, G-CSF although IL-8 and IFN-γ was not changed. Lysozyme hydrochloride inhibits pro-inflammatory cytokines in Epithelial cells infected with Respiratory Syncytial Virus, and may affect to airway inflammation.