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.