International Journal of Pharmaceutical Sciences and Drug Research

133-140

Authors: Priti Girotra, Shailendra Kumar Singh*

Katira gum, a natural polysaccharide resembles guar gum in chemical composition and is susceptible to degradation by colonic microflora. Azathioprine is used in the treatment of inflammatory bowel disease, ulcerative colitis and Crohn’s disease. Present investigation was undertaken to design Katira gum oral colon targeted matrix tablets containing azathioprine, in order to maximize its therapeutic efficacy. Central composite design (software design expert v. 8.0.7.1) was employed to optimize the formulation for maximum drug release in colon. The optimized batch tablets obtained were further coated by Eudragit S100 to minimize the drug release in upper part of GIT. The uncoated matrix tablets released around 20-50% of the drug in the physiological environment of stomach and small intestine but released all its contents in the colon. The coated optimized formulation exhibited a release of only 5-35% in stomach and small intestine and almost all drug in simulated colonic dissolution media. The drug release kinetics followed Korsmeyer-Peppas model, indicating the drug release mechanism through combined diffusion and erosion mechanism. The results suggested that Katira gum can be a good carrier for colon targeting owing to its moderate viscosity, biocompatibility and biodegradability which could be successfully degraded by the microbial flora in the colon.

146-151

Authors: Preethi N*, Sujatha S

A novel type of elementary osmotic pump [EOP] tablet for efficient delivery of poorly water-soluble drug, glipizide has been designed. Drug release from the system, called Swellable Elementary Osmotic Pump [SEOP], is through a delivery orifice in the form of a very fine dispersion, ready for dissolution and absorption. SEOP tablets were prepared by compressing the mixture of micronized drug and excipients into convex tablet. The effect of wetting agent, swelling agent, osmotic agent and hydrophobic plasticizer on the release rate were investigated. The release behavior of glipizide from different formulations of this dosage forms were studied at pH 6.8 for a period of 24 hours. The drug release profile from osmotic devices showed that the type of polymer in the core formulation can markedly affect the drug release. When the amount of HPMC E50-LV was increased from 30 to 60 mg, decrease in drug release was observed. Increasing the amount of wetting agent to an optimum level of 45 mg significantly increased the release rate and improved zero order release pattern of glipizide. Increasing the concentration of Dibutylphthalate [DBP-30%] in the semi permeable membrane of the device retarded the release rate of glipizide but gave best results at the 20% concentration. Based on the SEM studies, optimized orifice diameter was found to be 500µm. Compared with the marketed Glipizide extended release tablet; GF2 gave the best release rate for 24 hours. The bioavailability studies for glipizide SEOP and Glipizide extended release tablet was carried out in albino rabbits and there was a good in-vivo and in-vitro correlation for GF2 as shown by the higher Cmax and AUC values. Thus a novel SEOP was successfully formulated for glipizide to achieve zero order drug release over a period of 24 hours.

158-164

Authors: Phyllis Elsie Dadzeasah, Charles Ansah*

Spathodea campanulata, well known for its traditional medicinal uses was investigated for hepatoprotective activity against acetaminophen-induced hepatic damage in mice. Six groups of mice were pre-treated with 100, 300 and 625 mg/kg of the aqueous extract of Spathodea campanulata stem bark, N-acetyl cysteine (300 mg/kg; p.o) or distilled water for 5 days before they were intoxicated with a single dose of acetaminophen (600 mg/kg; p.o). Alanine aminotransferase, Aspartate aminotransferase and total protein levels were measured in serum, glutathione peroxidase, superoxide dismutase and total cytochrome P450 levels were measured in liver homogenate and liver histology was also observed on liver sections. Total liver cytochrome P450 levels in Spathodea campanulata extract, distilled water, ketoconazole or phenobarbital-treated animals were also measured. Significant hepatoprotection was obtained against liver damage induced by acetaminophen as evident from decreased serum levels of Aspartate transaminase, Alanine transaminase and increased levels of total protein in the combined acetaminophen and extract treated groups and the acetaminophen and N-acetylcysteine-treated groups compared to the acetaminophen only controls. The decrease in serum antioxidant enzymes; glutathione peroxidase and superoxide dismutase levels caused by acetaminophen was significantly reversed by the extract. The results correlated well with the histopathology of liver from treated and control animals. The extract also caused considerable inhibition of total CYP450, the enzymes involved in the activation of acetaminophen. The present results indicate that Spathodea campanulata protects the liver against acetaminophen-induced hepatotoxicity by enhancing antioxidant protection capacity and interfering with the bio-activation of acetaminophen.

170-174

Authors: N. Shruthila, Priya Narayan, D. Jagadeesh Kumar, H. G. Nagendra*

The aggregation of Amyloid beta peptides is considered as one of the causative events in the pathogenesis of Alzheimer’s disease (AD). Polyphenols present in different plant sources, which have acclaimed therapeutic values, are known to inhibit the formation of Amyloid fibrils. Hence, docking studies with different polyphenols were carried out to appreciate their binding modes and plausible molecular interactions. The results reveal a consensus pattern of association, exhibiting that all the ligands preferentially dock to the metal coordinating residues in the peptide fragments. In fact, the metal interacting geometries in the Aβ segments are known to be implicated in aggregation events. Further, due to non-specific binding, these polyphenols are expected to have a competitive inhibitory efficacy over a range of amyloid peptide fragments. Thus, these findings suggest that the polyphenolic compounds could become promising lead molecules that aid in the development of inhibitors and neuroprotectors towards prevention of amyloid fibril formations and AD.

179-183

Authors: S. Dhanure, A. Savalia, S. K. Nayak*, A. K. Das, S. K. Kotha, A. K. Patra

The bioequivalence between test and reference Tramadol and Paracetamol (37.5 + 325 mg) tablets was determined in 36 healthy subjects after a single dose in a randomized crossover study under fasting condition. Plasma concentrations were monitored over a period of 24 hour after the drug administration by validated LC/MS/MS analytical method. The pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞, AUC0-t / AUC0-∞, Tmax, Kel and t½ were determined from plasma concentration time profile of both formulations and found to be acceptable. The calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the test and reference products. The analysis of variance did not show any significant difference between the two formulations and 90 % confidence intervals for the ratio of Cmax (92.29 -104.18 %), AUC0-t (99.52 - 104.11 %) and AUC0-∞ (99.05 - 104.22 %) for tramadol and Cmax (93.56 - 110.27 %), AUC0-t (96.37 - 102.70 %) and AUC0-∞ (97.22-103.28 %) for paracetamol test and reference products were within the 80 – 125 % interval, satisfying the bioequivalence criteria the US Food and Drug Administration Guidelines. These results indicate that the test and the reference products of Tramadol and Paracetamol are bioequivalent.

187-193

Authors: OO Johnson1*, GA Ayoola1, T Adenipekun2

The synergistic effect in the antimicrobial activity of the volatile oil blend from Garlic clove (Allium sativum) and tangerine fruits (Citrus reticulata) were investigated and compared to antimicrobial activity when the individual volatile oils were used alone. The volatile oils were extracted by steam distillation using Clevenger hydrodistillator apparatus and each oil was tested for antimicrobial activity, while equal volume of these oils were blended and tested for antimicrobial activity. The microorganisms used include, Staphylococcus aureus isolate, Escherichia coli isolate, Pseudomonas aeruginosa, Salmonella typhi, Candida albicans isolate, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Candida albicans ATCC 90028. The Minimum Inhibitory Concentrations (MICs) ranged from 9.31×10-13 – 7.88 mg/ml for garlic oil, 0.16 – 2.66 mg/ml for tangerine oil and 5.95×10-31 – 1.24 mg/ml for the essential oil blend. Minimum Inhibitory Concentration indicated that the Garlic oil and Tangerine oil blend was better at inhibiting the tested microorganisms than the individual oils except for Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. The Gas Chromatography-Mass Spectrometry revealed Trisulphide, di-2-propenyl (30.32%) as the major component in the garlic oil extract and 3-Cyclohexene-1-methanol, alpha 4-trimethyl (33.38%) in the tangerine oil. While the equal volume of the oil blend also revealed Trisulphide, di-2-propenyl (15.92%) and 3-Cyclohexene-1-methanol, alpha.4-trimethyl (12.02%) as the major constituents though in lower concentrations. Hence, the more potent antimicrobial properties demonstrated by the oil blend can be exploited further with a view to generate new effective antimicrobial compounds.

84-87

Authors: Ruchika Nandha*

Lidocaine, a known local anaesthetic agent has been demonstrated to possess significant efficacy in managing asthma due to its anti inflammatory and direct spasmolytic actions. Various clinical studies have been conducted to assess the role of Lidocaine in asthma management with convincing results showing reduction in steroid dose or discontinuation of steroid therapy associated with improvement in quality of life, marking this old drug as a novel efficacious, fast and safe addition in armamentarium of anti asthma drugs. Inhaled Lidocaine when given alone causes biphasic effect on bronchi with initial bronchoconstriction followed by bronchodilatation. Treatment with combination inhalers, containing Lidocaine and a long-acting β2- agonist seems the safer and more reliable alternative to minimise adverse effects of initial reflex bronchoconstriction caused by inhaled Lidocaine. This review elucidates the available evidence on efficacy and safety of inhaled Lidocaine after analyzing various clinical studies. Searches of pubmed, Cochrane database, Medscape, Google and clinicaltrial.org were made for terms like Lidocaine and bronchial asthma.

96-100

Authors: Sunakar Panda*, D. L. Singh, S. K. Nayak

Some 1-Nicotinoyl-4-aryl-3-methyl 3a, 4-dihydropyrazole [3, 4c] pyrazoles were synthesised and their inclusion complexes were prepared with β-cyclodextrin. The compounds and their inclusion complexes were characterised by the study of their physical and spectral properties. The determination of stability constant of inclusion complexes and other thermodynamic parameters such as change in free energy, change in enthalpy and change in entropy, suggested the inclusion complex formation to be thermodynamically allowed. Further, the compounds and their inclusion complexes were screened for antibacterial activities against Escherichia coli (MTCC 40), Bacillus subtilis (MTCC 441), Staphylococcus aureus (MTCC 87) and Proteus vulgaris (MTCC 426). It was found that that the formation of inclusion complex causes an increase in antibacterial activity.

105-107

Authors: Singh Sunil*, Choudhary Nisha, Rai Jyoti, Inamullah, Sharma Surabhi, Yadav Ajit Kumar, Gautam Hemendra, Chaturvedi Shashank, Agrawal Vipin Kumar

A simple, sensitive and precise isocratic ultra performance liquid chromatographic method for the analysis of Lansoprazole has been developed, validated and used for the determination of compounds in commercial pharmaceutical products. The separation was carried out isocratically on a C18 column utilizing a mobile phase consisting of methanol: water (80:20 v/v) at a flow rate of 1.0 mL/min with UV detection at 284 nm. The retention time of Lansoprazole was found to be 3.905 min. The described method was linear over a concentration range of 50-30 μg/ml (r2 =0∙998) for the assay of Lansoprazole. Results of analysis were validated statistically. The results of the study showed that the proposed RP-UPLC method is simple, rapid, precise and accurate, which is useful for the routine determination of Lansoprazole in tablet dosage form and in its pharmaceutical dosage forms.

113-119

Authors: J Sojitra1, P Dave1, K Pandya2*, V Parikh2, P Patel2, G Patel2

Standardization of Ayurvedic formulations is an important step for the establishment of a consistent biological activity, chemical profile, or simply a quality assurance program for production and manufacturing of herbal drugs. WHO specifies guidelines for the assessment of the safety, efficacy and quality of herbal medicines as a prerequisite for global harmonization. Hence it is very essential to ensure that each packet sold in the market is standardized. In this research work, a polyherbal formulation (PHF), Caspa Drops has been taken to establish its standardization level using various physico-chemical parameters. For raw material various parameters such as pH, Moisture content, ash values, HPTLC fingerprinting, assays of marker compounds etc. were carried out to confirm their quality and potency. The presence of the raw materials in the finished product was carried out with the aid of sophisticated instruments. Study results revealed that product was well standardized at selected analytical parameters. All the tests were carried out in triplicates after which their SD was calculated. All the raw materials as well as finished product were found free from heavy metal and microbial contaminants.

125-128

Authors: Renjana P. K.*, John E. Thoppil

Cytotoxic and genotoxic effects of methanolic extract of the roots of Strobilanthes heyneanus Nees have been studied on the root meristem cells of Allium cepa. Roots of A. cepa were exposed to different concentrations (0.01%, 0.05%, 0.1% and 0.5%) of the extract for ½, 1, 2 and 3 h. Mitotic index and chromosomal aberrations in the treated cells were analysed. Distilled water has been used as control. Mitotic index val¬ues were decreased with increasing concentrations and longer treatment durations compared to the control (p < 0.05) in dose and time dependent manner. Additionally, different abnormal mitotic figures were observed in all treatments. Among these abnormalities were nuclear and chromosome lesions, anaphase bridges, C-mitosis, pulverization, stathmo-anaphases, diagonal orientation, chromosome fragments etc. The total percentage of aberrations generally increased with increasing concentrations of the extract and longer durations of exposure. The observations of the present study are a clear indication of clastogenic and non-clastogenic property of the extract, which is evident from the direct actions on the chromosomes and manifestation of spindle abnormalities.

41-44

Authors: Baby Joseph*, Jency George, Jeevitha Mohan

Mimosa belongs to the taxonomic group Magnoliopsida and family Mimosaseae. In Latin it is called as Mimosa pudica Linn. Ayurveda has declared that its root is bitter, acrid, cooling, vulnerary, alexipharmic. It is used in the treatment of leprosy, dysentery, vaginal and uterine complaints, and inflammations, burning sensation, asthma, leucoderma, fatigue and blood diseases. Decoction of root is used as gargle to reduce toothache. It is very useful in diarrhea (athisaara), amoebic dysentery (raktaatisaara), bleeding piles and urinary infections. This review gives a brief compilation of its phytochemical and pharmacological activities.

50-55

Authors: Mahananda Sarkar1, Prova Biswas1, Amalesh Samanta2*

The present study was designed to evaluate the hypoglycemic activity of the aqueous extract of Leucas indica Linn. on streptozotocin induced diabetic rats. The extract showed a significant dose depended (200 and 400 mg/kg b.w, orally) reduction in fasting blood glucose level, comparing with reference drug, glibenclamide (0.5 mg/kg b.w, orally). In addition, the changes in body weight, analysis of serum biochemical parameters like lipid profile, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, total proteins, bilirubin, urea and alkaline phosphatase were assessed for each group of animals and the significant differences were observed when compared with control groups. Finally, in case of histopathological investigation of pancreas, liver and kidney from each group of rats showed a significant protection and regeneration of earlier streptozotocin induced cellular necrosis. This finding proves that the extract exhibits sufficient hypoglycemic activity along with improves streptozotocin induced negative body weight as well as normalize serum biochemical parameters and protect from cellular necrosis significantly.

62-66

Authors: Urvish H. Desai*, Arpit H. Patwari, Jaydeepkumar K. Maradiya, Mehul K. Sathawara, Bhanubhai N. Suhagia, Ishwarsinh S. Rathod

High performance liquid chromatography method was applied to the simultaneous determination of ciprofloxacin and dexamethasone. The chromatographic separation was achieved on reversed-phase C18 column(25 cm × 4.6 mm id, 5 µm) in the isocratic mode using methanol-water-triethylamine (55:45:0.6, v/v/v), pH adjusted to 3.0 ± 0.05 with orthophosphoric acid as the mobile phase at a flow rate 0.8 ml/min. Quantitation was achieved with UV detection at 254 nm. In the HPLC method, quantification was achieved over the concentration range of 3-18 and 1-6µg/ml, with mean recoveries of 99.94 ± 1.51 and 100.28 ± 1.25% for ciprofloxacin and dexamethasone respectively. The proposed methods were successfully applied for the analysis of synthetic mixtures and pharmaceutical formulations of ciprofloxacin and dexamethasone without any interference from common excipients.

70-77

Authors: T. K. Laha1*, G. Mishra2, S. Sen1

A simple and sensitive reverse phase high performance liquid chromatographic (RP-HPLC) method for determination of duloxetine and twelve of its metabolites, Sulfate conjugate of 4-hydroxy duloxetine (M1), N-desmethyl duloxetine (M2), Glucuronide conjugate of 4-hydroxy duloxetine (M3), Glucuronide conjugate of 6-hydroxy duloxetine (M4), Glucuronide conjugate of 4,6-dihydroxy duloxetine (M5), Glucuronide conjugate of 5-hydroxy-6-methoxy duloxetine (M6), 4-Hydroxy duloxetine (M7), 5-Hydroxy duloxetine (M8), 6-Hydroxy duloxetine (M9), Thienyl alcohol (M10), Glucuronide conjugate of 5-hydroxy duloxetine (M11), Glucuronide conjugate of dihydrodiol duloxetine (M12) in Wistar rat plasma, urine, feces and bile was developed. Analysis was carried out on a µ-Bondapak C18 column (250mm × 4.6mm, 5µm particle size) using methanol: phosphate buffer (pH 7.8, 50 mM) (7:3 v/v) as the mobile phase at a flow rate of 1ml/min. Detection was carried out at 221 nm with an UV detector. The above metabolites were characterized by retro-synthesis followed by 1H-NMR, 13C-NMR and M.S study for structure confirmation and finally injected separately into the HPLC system. All the twelve retention time matches with the metabolites present in the plasma, urine, feces and bile sample. This method has also been successfully applied in the pharmacokinetics study of duloxetine after orally administrating the duloxetine to Wistar rat.

01-13

Authors: Saurabh Srivastava, V. R. Sinha*

Injectable biodegradable polymeric microspheres of Stavudine were prepared using different viscosity grades of PLGA 50:50 (RESOMER® 504H and RESOMER® 502H) by solvent evaporation technique with different drug/polymer ratios. Tailored release of Stavudine facilitates reduction in symptoms of HIV infection and delay AIDS progression by reducing viral load to undetectable levels for extended period of time. The influence of formulation variables on microparticle characteristics like polymer type and concentration, vehicle type, polymer solution/vehicle volume ratio, surfactant concentration and drug to polymer ratios were evaluated. Microspheres were evaluated for yield, entrapment efficiency, particle size and in-vitro release behavior as well as characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), residual solvent analysis and confocal laser scanning microscopy (CLSM). Microspheres showed excellent surface topography with uniform distribution and structural integrity of the drug having the entrapment efficiency of 90.96 ± 1.09 and mean particle diameter below 65μm. Drug release kinetics data were obtained from various kinetic models and best explained by “Korsmeyer-Peppas equation” for both the polymers which depicted that drug release mechanism is anomalous transport, i.e. diffusion as well as polymer relaxation. Drug release from microspheres exhibited the characteristic release pattern of a monolithic matrix system with 90-100% drug release in 6-8 weeks demonstrating the feasibility of prolonged delivery of Stavudine using biodegradable microspheres for parenteral depot system.

18-22

Authors: A. B. Ruzilawati*, W. N. Wan Yusuf, N. Ramli, Z. Hussain, A. H. G. Rasool

A simple reverse-phase high-performance liquid chromatographic method has been developed for the determination of morphine in human urine using codeine as internal standard. After solid-phase extraction (SPE), the compounds were separated on a reversed-phase Acentis Express C18 column (150mm × 4.6mm, 2.7µm) equipped with a guard column (2.7 µm, 5 mm × 4.6 mm). The channel on the UV detector was configured to acquire data at 285 nm. The mobile phase was composed of acetonitrile-sodium acetate (pH 4; 0.01M) (10:90, v/v). The flow rate was 0.6 ml/min. Injection volume was 30 ml. The run time was set at 10 min. The retention time for morphine and codeine were approximately 3.4 min and 7.2 min, respectively. The calibration curve was linear over the concentration range of 150-2000 ng/ml with good linearity. Limit of detection (LOD) and quantification (LOQ) in urine were 50 and 150 ng/ml, respectively. Recovery was greater than 85%. The inter-day precision was from 9.27% to 12.53% and the intra-day precision ranged from 1.63% to 4.58%. The inter-day accuracy ranged 81.45% to 109.88% and intra-day accuracy ranged from 81.56% to 106.69%. The stability studies showed that morphine was stable up to one month in urine. This method was applied to determine morphine concentration in human urine for toxicology analysis.

28-31

Authors: Upadhyay Vipul, Sharma Neeru, Tiwari Kumar Amit, Joshi H. M., Malik Amreesh, Singh Brijpal, Kalakoti Singh Bahadur

Different extract of Convolvulus pluricaulis choisy, (Methanol, hydro-alcohol (50%) and water) were prepared and tested of scopoletin. The maximum scopoletin content was observed in 50% ethanolic extract followed by methanol and water extracts. It was 0.1738%, 0.0932% and 0.0435% in hydro-alcoholic, Methanol and water extract respectively. A simple HPLC (High Performance Liquid Chromatography) was developed for the determination of Scopoletin in Convolvulus pluricaulis choisy. Shankhpushpi is an astringent, hot aphrodisiac and a nervine tonic. It improves strength, digestive power, helpful in epilepsy, insomnia, heart disease and hemetemesis. Analyte separation and quantification were achieved by high-performance liquid chromatography (HPLC) and UV detection at 366 nm. The method involves the use of C18 column (Phenomenex, 250 mm × 4.6 mm, 5µm) with isocratic mixture of methanol and water containing 0.1% v/v formic acid in the ration of 30:70. Linearity was observed in the range of 20-100 ppm with correlation coefficient of 0.9961. Relative standard deviation of linearity of the method was found to be 1.29%. Detection limit was 5.0 ppm and quantification limit was 7.5 ppm. The repeatability of the method was found to be 0.71%. Recovery values from 99.10 to 100.1% indicate best accuracy of the method.

36-37

Authors: Kundan Kumar*, I. N. Mishra, Sandhya Jha

Escherichia coli strain ATCC 8739 is an important strain of pharmaceutical and biotechnological industries. We studied the viability of culture suspension of Escherichia coli strain ATCC 8739 at 2 to 8°C up to 360 days in 0.9% w/v NaCl. The culture suspension containing 10000 cfu/ml used in the study was stored at 2 to 8°C for 360 days in 0.9% w/v NaCl. Using 10µl of above culture suspension, the viable count was made by the pour plate technique using Soyabean Casein Digest Agar medium in fixed interval of time during the 360 days storage period. During the storage period, population of Escherichia coli strain ATCC 8739 decreased from 10000 cfu/ml to 9900 cfu/ml during the first 30 days, whereas the population decreased to 0 cfu/ml in 360 days. Findings emanate from the study indicates that 30 days storage period of Escherichia coli strain ATCC 8739 at 2 to 8°C in 0.9% w/v NaCl is suitable for laboratories testing purposes on account of fact that in 30 days storage period, population of Escherichia coli strain ATCC 8739 decreased from 10000 cfu/ml to 9900 cfu/ml which is very low.