PHARMACEUTICAL SCIENCES
Year:2005 | Volume:- | Issue:2|Papers Count:13

The aim of this study was to prepare fusogenic liposome as a drug delivery carrier for CyA METHODS: In this study liposomes containing CyA were prepared by using dipalmitoylphosphatidylcholine (DPPC) and cholesterol via solvent evaporation method and for fusogenic liposomes dioleoylphosphatidylethanolamine (DOPE) was added to the formulation. For sizing of liposomes, polycarbonate filters with exact size of 1000, 400 and 100 nm was used. For liposome characterization, liposome size was determined by using particle size analyzer and encapsulation percent was evaluated during two months. Finally in vitro immunosuppressive effects of liposome's and aqueous solution of CyA were compared on human T-cells by MTT [3- (4, 5- dimethylthiazol- 2-yl)-2, 5-diphenyl tetrazolium bromide] test RESULTS: Light microscopic evaluation of the liposome formulations showed that the liposomes are multi lamellar vesicle (MLV). The sizes of non-fusogenic and fusogenic liposomes were 1.76±0.006 and 2.122±0.004 µm, and their percent of encapsulation were 79.7±3.00 and 85.67±9.46 %, respectively. In vitro immunosuppressive evaluation by T-cell culture was showed that fusogenic liposomes have more inhibitory effects on T-cell proliferation than non-fusogenic liposome and aqueous solution of CyA. IC50 of MLV, 1000,400 and 100 nm of fusogenic liposomes were 6.151x10-6, 4.123x10-5 1.461x10-4 and 1.276x10-4mM, respectively. CONCLUSION: In this study high encapsulation percent and fairly stable liposomes encapsulated with CyA were prepared and the results showed fusogenic liposomes could be a suitable delivery system for CyA.

OBJECTIVES: In the previous study it has been shown that adrenergic drugs have antinociceptive effect. Ephedrine (ephedrine sulfate) is both an a and a β adrenergic agonist; in addition, it enhances release of norepinephrine from sympathetic neurons. Opioids have different side effects, particularly respiratory depression and dependency. The purpose of the present study was to determine the possible action of ephedrine on morphine antinociception and tolerance induced to morphine antinociception. METHODS: To measure antinociception, different doses of morphine (3, 6 and 9 mg/kg, ip), ephedrine (10, 20, 30 mg/kg, ip) and ephedrine (10, 20, 30 mg/kg,ip)+morphine (3,6 mg/kg, ip) were injected. To develop a tolerance to morphine, antinociception animals received morphine (30 mg/kg, ip) once a day for four days. A test dose of morphine (9 mg/kg, ip) was tested on day 5 (24 h after the last dose of 50 mg/kg morphine). RESULTS: Intraperitoneal (ip) injection of different doses of morphine (3, 6 and 9 mg/kg, ip), ephedrine (10, 20, 30 mg/kg, ip) induced a dose dependent antinociception. The responses induced by morphine were increased by ephedrine. Morphine (3mg/kg, ip) in combination with ephedrine (10 mg/kg, ip) tended to elicit higher response (equal to morphine 6 mg/kg). Different doses of ephedrine (10, 20, 30 mg/kg, ip) showed a significant (P<0.001) decrease on morphinetolerance. CONCLUSION: It can be concluded that stimulation of adrenergic receptors are at least part of the ephedrine antinociception, and stimulation of these receptors attenuate tolerance induced to morphine antinociception.

OBJECTIVES: The aim of this study was to evaluate the role of central serotonergic system on the development of tolerance to morphine antinociception. METHODS: Experiments were performed on adult male wistar rats weighing between 200 and 250g. The control rats (n=8) had daily i.p. injection of morphine (5mg/kg) and the Hot-Plate test for 30 and 60 min subsequently and record in time (latency time). In the sham and test rats following induction anaesthesia, rats were secured in a stereotaxic frame with ear and incisor bars. Then a guide cannula was implanted into the DRN or MRN separately in rats (n=8). Coordinates for the DRN and MRN were taken according to Paxinos and Watson rat brain atlas. In the sham groups, 30 minutes after i.p. Injection desipramine (10mg/kg), 1µl/2min of 5, 7- dihydroxytryptamine vehicle (saline + oscorbic acid 10%) was injected into the nuclei. In test groups after the injection of desipramine, 4µg/1µ1/2 minof 5, 7-DHT was injected into the nuclei. Daily injection of morphine and Hot-Plate test was performed 5 days after the recovery of the rats. At the end of the experiments in the all rats methylen blue (1%) was injected into the nucleuses, the brains were removed and were fixed in the formalin solution (5%). Thereafter the injection sites were studied histologically. RESULTS: The results of this study showed that the tolerance to analgesic effect of morphine in the intact and control groups began almost 10 days after the daily injection of morphine but in DRN and MRN-lesioned rats it occurred at 19th and 21st days respectively. Data was analyzed and statistically significant differences were found between the test and control (P<0.001) or the sham groups (P<0.05). But there were no significant differences between the intact and the control groups. CONCLUSION: In conclusion these findings findings show that the serotonergic nerves lesion delay development of tolerance to morphine analgesia and decline the need for increasing analgesic dose of morphine to obtain the early effects of morphine.

OBJECTIVES: Streptokinase is a protein produced by β-hemolytic Streptococci. It has no intrinsic enzymatic activity, but it forms a stable complex with plasminogen, which converts plasminogen to plasmin. It is administrated in the management of deep vein thrombosis, arterial thrombosis and embolism, pulmonary embolism, acute evolving transmural myocardial infarction and occluded AV (Atrial-Ventricular) cannula. The common allergic reactions include urticaria, itching, headache, musculoskeletal pain, flushing, nausea, fever, bronchospasm, and anaphylactic reactions. The hematological side effects are bleeding (involving the GI tract, GU tract), unstable tension, atrial or Ventricular disarrhythmias. METHODS: In this retrospective study, the questionnaires were completed for all 332 inpatients that had received streptokinase during 1999-2001. According to data from patient's files the questionnaire were filled. RESULTS: Among 332 patients received streptokinase, 76.81% was male and 22.89% was female, that 18.97% of males and 4.21% of females showed side effects. Incidence of side effects was 10.47% in 1999, 10.74% in 2000 and 50% in 2001. The incidence of side effects in 2001 was varied and high. Most of the side effects were allergic reactions. The source of streptokinase during that time was Cuba under trade name of Heberkinase. CONCLUSION: These results may indicate that the used batches in 2001 were different from previous and probably contained more impurities.

OBJECTIVES: Urinary Tract Infections (UTIs) occur commonly in pediatric population. Ciprofloxacin is a fluoroquinolone antibacterial agent and an attractive alternative for the treatment of UTI in children. Although Ciprofloxacin is widely used for treatment of UTI in adults, few data is available regarding the use of Ciprofloxacin in children. This report describes the in vitro antibacterial effect of Ciprofloxacin on common strains of urinary tract infections and compares it with other drugs. METHODS: In a prospective study, 213 bacteria were collected from patients with urinary tract infections in Microbiology Laboratory of Tabriz Pediatric Medical Center during 2003-2004. Then a suseptibility test was carried out with the use of standard disks (Kirby-Bauer method) for Ciprofloxacin and was compared with Co-trimoxasol, Nalidixic acid, Nitrofurantoin, Amikacin, Gentamicin and Ampicillin. The Mean age of patients was 4.5 years old. During 9 months 213 patients with UTI were admitted (59% female and 41% male). The number of the cultures belonging to E.coli were 169 (79%), Klebsiella pneumonia 19, Enterobacter cloacae 11, Pseudomonas aeruginosa 9, Klebsiella oxitoca 3, Proteus mirabilis 2. RESULTS: It was shown that 4.3%, 18.3%, 22.5%, 26.7%, 40%, 64.7% and 95% of the bacteria were resistant to Ciprofloxacin, Amikacin, Nalidixic acid, Nitrofurantoin, Gentamicin, Co-trimoxasol and ampicillin, respectively. According to the inhibitory effect ofCiprofloxacin on the bacterial isolations and in comparison with the other antibiotics, this study demonstrated a highly broad spectrum of Ciprofloxacin. CONCLUSION: Since the tested strains proved to be highly sensitive-to Ciprofloxacin and also based on some data about safety use of this antibiotic in children, it is possible to consider Ciprofloxacin, as a drug of choice in etiotropic therapy of children with UTI. Ciprofloxacin Resistant E.coli (4.3 %) have been developed against this antibiotic in this area.

OBJECTIVES: Proxicam is a poorely soluble, high, lypermeable drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal. In this study we tried to improve the dissolution rate of a poorly water soluble drug, piroxicam, by solid dispersion systems using PEG2000, PEG4000, PEG6000 and PEG20000 as hydrophilic carriers. The goal was to investigate the effect of PEG molecular weight of carrier on the dissolution properties of piroxicam. METHODS: The solid dispersions were prepared by melting method. The evaluation of the dispersions properties was performed using solubility measurements, dissolution studies, FT-IR spectroscopy and powder X-ray diffractometery (PXRD).RESULTS: Solubility studies revealed a marked increase in the solubility of piroxicam with an increase in PEG molecular weight as well as concentration. This may arise from the modification of polarity of the medium, hence solubilizing effect of carriers. An increased dissolution rate of piroxicam at pH 1.2 and 7.2 was observed when the drug was dispersed in these carriers. The dissolution rate of piroxicam was markedly increased from solid dispersion of PEG2000, PEG4000, PEG6000, PEG20000 but dissolution rate was decreased as molecular weight or concentration of PEG increased, which may be attributed to the increased viscosity around the solid particles. Data from the X-ray diffraction and FT-IR spectroscopy showed that piroxicam crystallinity was decreased in the solid dispersions. CONCLUSION: Dissolution byhavior and hence absorption rate piroxicam can be considerably enhanced by solid dispersion technique.

OBJECTIVES: Improvement on the taste of liquid dosage forms has always been important in respect to the acceptance of patient. Many methods including the addition of flavoring agents can solve the problem of the unpatability of dosage forms making them acceptable to the patients, the objective which was followed at the present study. METHODS: The patability and acceptance of acetaminophen syrups prepared by three domestic factories using different flavoring agents (I, I, III) were evaluated in 50 healthy adult males and females in the age ranges of 20-25 years old. The tested samples were 120 mg 15ml acetaminophen syrups flavored by orange oil and raspoeny extract. RESULTS: Generally recommended procedures for taste test were followed and the results showed taste preference\for one of the factories (I), which had used raspbeny extract as flavoring agent. The significance of the results was checked with chi-square statistical analysis and type one error (a= 0.05). It may be needed to mention that the preferred flavor by volunteers was accorded with what B.P. used in this pharmacopoeia for flavoring acetaminophen liquid dosage form, which confirms the results of this study. CONCLUSION: The findings of the study showed that the acceptance for acetaminophen syrup flavored with raspbeny extract was better compared to those of flavored with orange oil. The raspbeny extract did not allow acetaminophen to have contact with taste buds on the tongue and the patients accepted dosage form made with this flavor. Taste improvement of oral liquid dosage forms with orange oil needs enough concentration of this flavor.

OBJECTIVES: For poorly soluble, highly permeable (Class II) drugs, such as indomethacin, the rate of GI absorption is often controlled by the dissolution rate in the gastrointestinal tract. There are several techniques to enhance the dissolution of poorly soluble substances. Among them, the technique of liquisolid compact is a promising technique to increase dissolution rate of poorly soluble drugs. The aim of this study was to asses the use of liquisolid technique in enhancing dissolution rate of indomethacin and evaluation of effect of various carriers and solvents on drug release from its liquisolid 'tablets. METHODS: In this study, the dissolution behaviors of indomethacin from liquisolid compacts were investigated at two different media Simulated Gastric Fluid (SGF, pH=1.2) and Simulated Intestinal Fluid (SIF, pH=7.2). To this end, several formulations of liquisolid compacts containing variety of carriers (microcrystalline cellulose, lactose, starch, sorbitol and manitol) and nonvolatile solvents in various ratios of drug: solvent (polyethylene glycol 400) were prepared and dissolution profile of them were studied, Results: The results showed that liquisolid compacts demonstrated a considerably higher drug dissolution rates than those of conventionally made capsules and directly compressed tablets. This was due to the increased wetting properties and surface of drug available for dissolution. The results showed that the dissolution rate of the drug in SIF is better than SGF medium. In the evaluation of the kind of solvents, there were not any significant differences between solvents in SIF medium but in SGF, the formulation containing propylene glycol as solvent had a better dissolution profile. Among the carriers, also microcrystalline cellulose had better liquid retention potential, but in both SGF and SIF media, there was no significant difference between the dissolution rates of formulations. CONCLUSION: It can be concluded that the liquisolid technique can be used to increase the dissolution rate of poorly water soluble drugs.

OBJECTIVES: Lorazepam is a practically insoluble drug which its oral absorption is limited by the dissolution rate, therefore, increasing lorazepam dissolution rate may increase its bioavailability. Solid dispersions with, hydrophilic carriers are the most effective techniques for improving dissolution rate of poorly water soluble drugs. Hydrophilic surface active agents are a group of compounds which can act as suitable carriers for solid dispersions of poorly water-soluble drugs. METHODS: In this study, solid dispersions of lorazepam and three types of surfactants (SLS, CTAB and Myrj 52 as anionic, cationic and nonionic surfactants respectively) were prepared with different drug- carrier ratios (1: 0.1, 1:0.25, 1;0.5. 1:1 1:2 and 1:5). Solid dispersions were prepared using solvent evaporation method and 75% hydroalcoholic solution was used as solvent. In-vitro dissolution rates of the solid dispersions were measured using dissolution rate apparatus (USP II) and compared with pure drug, treated drug and physical mixtures with the same drug- carrier ratios. FT-IR and XRD spectra were taken from samples for determining of any drug- carrier interaction and crystalline changes during co-evaporation process respectively. RESULTS: The results showed a significantly higher dissolution rate of solid dispersions in comparison with pure drug, treated drug and physical mixtures with the same drug- carrier ratios as solid dispersions. 1:0.5, 1:1 and 1:5 drug-carrier ratios were determined as the best ratios for lorazepam- SLS, lorazepam- CTAB and lorazepam-Myrj52 solid dispersions respectively. FT-IR and XRD did not show any drug- carrier interaction and significant crystalline changes in drug during the processes respectively. CONCLUSION: solid dispersion techniques are very effective methods for enhancing dissolution rates of poorly water soluble drugs, and surfactants can be suitable carriers for them in solid dispersions.

OBJECTIVES: Uritca dioica (stinging nettle) has been used in Irarian traditional medicine in the treatment of diabetes. In this study the blood glucose lowering effect of uritca dioica leaves extract was investigated in wistar rats. METHODS: wistar rats were allocated in two groups of normal and diabetic (induced by streptozotocin; ip). Animals in each group were subdivided into two groups of 5 that received hydroalcoholic extract of Uritca dioica either interaperitoneally (ip) or orally. The blood glucose was determined by using a Glucometer. RESULTS: Oral and ip administration of hydroalcoholic extract of the plant showed a strong glucose lowering effect only on streptozotocin (STZ) induced diabetic rats. In contrast, the extract did not show hypoglycemic effect in normal rats. Even the extract in high doses produced a mild but a significant hyperglycemia in early hours after ip injection. Orally administrated extract in doses of 500 and 1000 mg/kg produced 20.8 and 23.7 percent reduction, respectively, in the blood glucose level 24 hours after diabetes induction. The decrease of STZ-induced hyperglycemia has reached to 33 and 44% of the control value 24 hours after the induction of diabetes with 25 and 50 mg/kg of ip injected extract. These effects were persistent during 48 hours. CONCLUSION: The results indicate that nettle has a significant hypoglycemic effect on STZ-induced diabetic rats a type II diabetic model.