Iranian Journal of Pharmaceutical Research
Volume:8 Issue: 4, Autumn 2009

The purpose of this study was to design and optimize an oral controlled release acyclovir mucoadhesive tablet, in term of its drug release and mucoadhesive strength. A 32 full factorial design was employed to study the effect of independent variables like Carbopol-934P and hydroxypropyl methylcellulose K100M, which significantly influence characteristics like swelling index, ex-vivo mucoadhesive strength and in-vitro drug release. Tablets were prepared by direct compression and evaluated for mucoadhesive strength and in-vitro dissolution parameters. In all the nine formulations studied, the exponent (n) varied between 0.5266 and 0.7110, showing non-fickian release behavior corresponding to coupled diffusion or polymer relaxation, resulting in a controlled and complete drug release up to 12 h. Both these polymers had a significant effect on the mucoadhesive strength of the prepared tablets, measured as the force of detachment against sheep gastric mucosa. Besides unraveling the effect of the two factors on the various response variables, this study helped in finding the optimized formulation with excellent mucoadhesive strength and controlled drug release. It can be concluded that by formulating mucoadhesive tablets of acyclovir, its complete release can be ensured prior to absorption window and hence the problem of incomplete drug release and erratic absorption could be solved by increasing the retention of drug in GIT for a longer duration.

The aim of this study was to develop an extended-release tablet formulation using a new in situ cross-linking method. The effects of polyvalent cations on theophylline release from tablets made with the polyanionic polymers sodium alginate and sodium carboxymethylcellulose, were investigated. Different miliequivalents of the di and tri-valent cation, Ca2+ and Al3+, were added to tablet formulations. The results of the dissolution study showed that incorporation of cations sustained the drug release. This is due to an in situ cross-linking between the polyanionic polymers and the added cation in tablet formulation. The drug release prolongation and the release kinetics were dependent on the nature of the polymers and the cations’ concentrations and valences. The drug release rate decreased by an increase in cation concentration. The combination of the two investigated polymers decreased the drug release rate to a higher extent in comparison with formulations containing each polymer alone. A zero-order drug release kinetic was observed in formulations containing 1:1:1 ratio of drug: Na alginate: NaCMC, and the investigated cations. These results showed that the in situ cross-linking by polyanionic polymers can be used for controlling the drug release rate.

Isosorbide dinitrate (ISDN) is an effective drug in treatment of angina pectoris. In this study a new generation of electron capture detector (non-radioactive) with a short, non-polar and wide-bore column was used for analysis of ISDN in human serum. ISDN was extracted from serum by a mixture of ether and ethyl acetate and concentrated at room temperature. The method was linear between 5-50 ng/mL. Recovery and accuracy were 99-108% and greater than 90%, respectively, and inter-day precision was lower than 13%. Pharmacokinetic parameters were analyzed after oral administrations of Isocor 40 mg sustained release tablet in comparison with Isoket Retard 40. The statistical results obtained from comparison of Cmax, Tmax and AUC parameters showed no significant difference between these two products and therefore they were reported to be bioequivalent. Further more, the method used was found to be sensitive and accurate in pharmacokinetic studies.

Four conformationally restricted analogues of pentamidine were prepared. Then, different concentrations (0.039, 0.078, 0.156, 0.312 and 0.625 mg/mL) of each compound and two positive controls (amphotericin B and pentamidine, 0.625 mg/mL), one negative control (culture medium) and one solvent control (DMSO) were prepared and placed in 24-well plates containing 50000 parasite per well. Promastigotes of Leishmania major were incubated over a period of 2 days at 25°C; subsequently, percent of viable parasite in each well determined spectrophotometrically using MTT assay. The average EC50 for compounds 4a,b and 8a,b in DMSO was 0.098, 0.410, 0.150, 0.720 mg/mL, respectively. The average EC50 for positive controls pentamidine and amphotericin B was found to be 0.062 and 0.026 mg/mL. The control solvent had no significant effect on L. major promastigotes. All compounds had significant effect compared to DMSO and were less potent than positive controls.

In the present work, the antinociceptive action was assayed in several experimental models in mice: writhing, formalin and hot plate tests. The crude alkaloid fraction (25, 50, 100 mg/kg) and in a dose-dependent manner significantly reduced the nociception by acetic acid intraperitoneal injection (P < 0.001). In the formalin test, the extract (50 and 100 mg/kg) also significantly reduced the painful stimulus in both phases of the test (P<0.001). Treatment with the extract (25, 50, 100 mg/kg) when given i.p. or pentazocine (5 mg/kg, s.c.) produced a significant increase of the reaction time in hot plate test. These result showed that the alkaloid extract of Solanum trilobatum contains active analgesic principles acting both centrally and peripherally.

Phytochemical investigation of the dichloromethane extract of the dried roots of Ferula badrakema resulted in the identification of one new and six known compounds. Known compounds were sesquiterpene coumarins: mogoltacin, feselol, badrakemin acetate, ferocaulidin, conferone and conferol acetate. The new compound was a sesquiterpene, named badrakemonin. The structures of these compounds were elucidated by extensive NMR spectroscopic methods including 1D-(1H and 13C) and 2D-NMR (HSQC, HMBC, and ROESY) as well as MS experiments.

Isolation of some potent anti-tumor compounds from medicinal plants has motivated researchers to screen different parts of plant for their anti-tumor effects. It has been reported that several species of conifers posses’ cytotoxic activities on some tumor cell lines. Here branchlets and berries of Juniperus foetidissima and J. sabina were collected, dried and ethanol extracts of them obtained using percolation. Extracts were dried in reduced pressure and cytotoxic effects of different concentrations (5, 10, 20 µg/ml) were evaluated by MTT assay against three tumor cell lines (Hela, KB, MDA-MB-468), using ELISA at 540 nm. The extracts of the branchlets of male and female of J.foetidissima and berries extract of J. sabina showed inhibitory activities against KB cells. Extracts of male branchlets of J. foetidissima and berries extract of J. sabina were cytotoxic (cell survival less than 50%) against Hela cell line. Regarding to MDA-MB-468, only the extract of male branchlets of J. foetidissima was cytotoxic. Extracts of J. sabina were not cytotoxic at tested concentrations. According to the results obtained by MTT assay, KB cells seem to be much more sensitive than the other cell lines.

Studies have demonstrated that plant extracts possess various biological characteristics, including immunomodulatory activity. Heracleum persicum Desf. (Apiaceae), a medicinal plant native to Iran, was studied for its immunomodulatory activity. Immunomodulatory activity of different doses of an aqueous extract of H. persicum, was evaluated in female Swiss albino mice. Mice were treated with three doses (50, 100 and 200 mg/kg body weight) for 5 days. Body weight, relative organ weight, delayed type hypersensitivity (DTH) response and haemagglutination titre (HT) were studied in various groups of animals. No significant body weight gain differences were recorded in various groups of animals. The results obtained show a significant increase (P < 0.05) in relative organ weight of spleen and liver, at doses of 50 and 100 mg/kg. No elevation in the levels of liver function test (LFT) enzymes and kidney relative weight was observed with the plant doses examined. The H. persicum extract elicited a significant increase (P < 0.05) in the DTH response at doses of 100 and 200 mg/kg. In the HT test, the plant extract showed a stimulatory effect at all doses, however these changes were significant at doses of 50 and 100 mg/kg. No mortality occurred with the tested doses. Overall, H. persicum showed a stimulatory effect on both humoral and cellular immune functions in mice.

Plants used for traditional medicine contain a wide range of substances which can be used to treat various infectious diseases. Hence, antibacterial activities of ethanolic extracts of 19 plant species were studied against multi-drug resistant clinical isolates using agar well diffusion method. Extracts of Liquidambar orientalis, Vitis vinifera, Rosmarinus officinalis, Punica granatum, Cornus sanguinea, Euphorbia peplus, Ecballium elaterium, Inula viscosa and Liquidambar orientalis showed broad-spectrum antibacterial activity with inhibition zones ranging from 8 to 26 mm. The most resistant organisms were Escherichia coli (E. coli) (Ampicillin-, amoxycillin- and sulfamethoxazole-resistant), Stenotrophomonas maltophilia (S. maltophilia) (Amoxycillin- and nalidixic acid-resistant) and Klebsiella pneumoniae (K. pneumoniae) (Ampicillin-, amoxycillin- and aztreonam-resistant), and the most susceptible species were Staphylococcus aureus (S. aureus) (Penicillin G- and oxacillin-resistant), Streptococcus pyogenes (S. pyogenes) (Penicillin G-, erythromycin- and clindamycin-resistant) and Pseudomonas aeruginosa (P. aeruginosa) (Sulfamethoxazole- and novobiocin-resistant), respectively. Minimum Inhibitory Concentrations (MIC) of crude extracts were determined for the seven highly active plants showing activity against methicillin resistant S. aureus (MRSA), E. coli, P. aeruginosa, S. pneumoniae and the reference bacteria (E. coli ATCC 11229 and Kocuria rhizophila ATCC 9341 NA). MICs of active extracts ranged from 8 to 14.2 mg/mL against one or other test bacteria.

Increased plasma cholesterol is known to be a major risk related to the development of coronary artery disease. The main purpose of this study was to determine possible effects of the ethanolic extract of aerial parts of Peucedanum pastinacifolium on the serum lipids in hypercholesterolemic rats. Experimental hypercholesterolemia was induced by feeding rats a cholesterol-enriched diet for 56 days. Hypercholesterolemic rats were classified into five groups. One group did not receive treatments and served as a control hypercholesterolemic group. The other four groups were fed the cholesterol-enriched diet in conjunction with 125, 250, 500 mg extract per kg of the body weight along with 20 mg atrovaststin per kg body weight, in a daily oral dose. A normal group of rats fed with a plain chow diet was also included in the study. After oral administration for 8 weeks, P. pastinacifolium extract produced significant decrease on serum total cholesterol, low-density lipoprotein cholesterol, triglyceride levels and atherogenic indices in hypercholesterolemic groups (P < 0.05). P. pastinacifolium extract had no effects on serum high-density lipoprotein cholesterol levels in these groups. It is concluded that the extract of aerial parts of P. pastinacifolium exhibits lipid lowering activity in hypercholesterolemic rats. However, further investigation would be necessary to evaluate the mechanism of action of the extract.