PHARMACEUTICAL SCIENCES
Year:2001 | Volume:- | Issue:1|Papers Count:12

Cardiovascular diseases are the main cause of mortality in most countries Comparing with age matched men the incidence of these diseases in fettling women and menopause women who take estrogen is low. This suggests a protective effect for estrogen in cardiovascular system. However the exact mechanism of this protective effect is not elucidated and is controversial. One of the possible mechanisms is the direct relaxing effect of es1rogen on vascular smooth muscle. The present study aims to identity the possible mechanism(s) of the vasorelaxant effect of 17B-estradiol on rat aorta. Rings of aorta 3-5 mm wide were prepared from male Wistar rats (250-350 g) and equilibrated in Krebs' solution under 2g tension (37°C; 95% O2, 5% CO2) for 60 min. Rings were contracted with. PGF2 (10 µM), an approximately EC80 concentration. When contraction was stable 17 B-estradiol was applied for 40 minutes. Relaxation was expressed as % reversal of contraction. For studying the possible effect of endothelium, prostaglandins, nitric oxide and classic estrogen receptors in the vasorelaxant effect of 17B-estradiol, the relaxant effect was assayed again in the absence of endothelium, and in the presence of indomethacin. N-nitro-L-arginine methyl ester (L-NAME). methylene blue, puromycin, actinomycin-D, cyclohexamide and tamoxifen. Denuding the endothelium of aortic rings or incubating them with indomethacin, L-NAME, methylene blue, puromycin, actinomycin-D, cyclohexamide and tamoxifen did not alter the vasorelaxant effect of 17B-estradiol significantly (P>0.05). Therefore, it would suggest that this acute relaxing effect of estrogeil is independent of endothelium, prostaglandin production, NO synthesis and genomic pathways. Further studies are needed to clarify the mechanism(s) by which 17B-estradiol relaxes vascular smooth muscle.

Methylcellulose, MC, initially increased slightly chemical stability of ampicillin, AM, in aqueous suspensions prepared nom pure drug powder and commercial drug powder for oral suspension which contained sucrose as well as other formulation ingredients when compared with the corresponding simple aqueous suspensions (without MC). After termination of this initial period the length of which was longer for the pure powder than the commercial powder, the drug stability was not affected significantly in pure powder suspensions by MC. However, MC increased considerably the rate of drug degradation in suspensions prepared from the commercial powder following the initial period. Degradation rate of AM in these suspensions which contained large amount of sucrose as sweetening agent depended on MC concentration. The higher the concentration the higher was the rate of AM decomposition. Because of the complexity of the situation, the stability data did not obey the zero order kinetics which is usually employed for linearization of the suspensions stability data. In an attempt to clarify the effect of MC on degration of AM, the apparent solubility of AM was measured in presence of MC. The result showed that MC increased aqueous solubility of AM indicating a soluble complex formation between AM and MC. The complication was also confirmed by a subtraction spectrophotometric method. Since, the degradation of drugs in suspensions usually occurs in the solution phase and according to previous findings sucrose catalysed the decomposition of AM, therefore, the increase in solubility of AM by MC in suspensions of the commercial powder might increase sucrose catalysed degradation of this antibiotic. MC could also enhance the viscosity of the suspensions and could decrease the decomposition rate of the drug through the reduction in collision rates of reacting molecules as it was evident in the initial periods. But, in AM suspensions prepared of the commercial powder which contained sucrose, during the post initial period the degrading effect of MC seemed to overweigh its stabilizing effect.

Phenol with its application in the preparation of many chemical compounds, drugs and sanitate agents is used. Therefore during pregnancy contact with phenol it can absorbe and produce, maternal toxicity and affect on embryonic evolution. The aim of this investigation was to study the teratogenic effects of phenol in the developing mouse. For this study 14 virgin mice balb/c were mated. The pregnant mice were divided to experimental and control group. Between 7 to 11 postmating days, 50 mg/kg phenol (merk) interaperitonealy injected daily in experimental and the same manner control group received physiological serum. At the last day of pregnancy, all of cases (experimental and control) were anestetised, sacrificed and their fetuses collected, coded and all of malformations examined. The results show a decrease of population and high incidence of various abnormalities (such as exencephaly, limbs and skeletal defects) in experimental fetuses in comparison with control group.

Suspensions are an important class of pharmaceutical dosage forms. These disperse systems present much formulation, stability, manufacturing and packaging challenges. For evaluation of excipient's effect on suspension stability, different formulations were prepared. These preparations composed of 5.22 g/100cc chloramphenicol palmitate (as drug model) and different amounts of NaCMC, propylene glycol, Tween 80, polyvinyl pyrrolidolle (PVP), Bovine serum albumin (BSA) and preserved water (Qs). The results showed a critical amount of suspending agent (0.4%), surfactant (0.4-0.5%) and vehicle (20-22.5%) for preparing a stable suspension. PVP and BSA showed an inhibition effect on crystal growth after freeze-thaw cycling technique.

Several studies have been shown that surfactants are able to increase release rate of drugs from HPMC matrices. The present study investigates the effects of various surfactants )nonionic surfactants e.g. Tween 80 with HLB=15 and Arlacel60 with HLB=4.7, sodium lauryl sulphate as an anionic surfactant and cetyl trimethyl ammonium bromide as a cationic surfactant) with different concentrations ranging from 0-10% w/w on the release rate of propranolol hydrochloride from HPMC matrices. The results showed that an increase in the concentration of the surfactant with opposite charge to the drug resulted in a reduction in the release rate of propranolol from HPMC matrices. It was also found that the surfactant with the same charge as the drug had not considerable effect on the release rate of propranolol. The use of nonionic surfactant with high HLB caused an increase in the release rate of the drug, whereas using the low HLB. surfactant produced a reduction in release rate. The increase in release rate of the drug in presence of surfactant is attributed to an increase in wettability of tablet surfaces, reduction in surface tension, micellar solubilization and increase in drug solubility. The reduction in release rate of the drug could be due to the formation of insoluble complex between the drug of gel layer around matrix and lipophilicity of the matrix surfaces. Studies on the release kinetic of the drug from HPMC matrices showed that both diffusion and erosion mechanisms are responsible for the release of propranolol.

Ethyl cellulose (EC) is a widely used polymer in the production of sustained release dosage form. This polymer has been used mostly in process of micro encapsulation and also in film coating of pellets and granules in order to control drug release rate. Recently the application of EC in the production of hydrophobic and inert matrices has been investigated and the factors affecting drug release from these matrices have been evaluated. The purpose of this study was to investigate the effect of polymer viscosity, polymer particle size and compaction force on the release of sparingly soluble drug (Diclofenac sodium) from ethyl cellulose matrices. The results showed that matrices prepared from higher viscosity grade of EC released their drug content in faster rate than matrices prepared from lower viscosity grade. All matrices disintegrated during dissolution test but the time taken for complete disintegration was dependent on viscosity of the polymer, being longer for lower viscosity grades of polymer. This was attributed to the decrease in tablet crushing strength with increasing viscosity of the polymer which facilitated the diffusion of dissolution medium into the matrices. Investigation of the effect of polymer particle size on drug release showed that matrices prepared from coarser particles released their drug content slower than those prepared from smaller particles. This effect was due to more rapid disintegration of matrices prepared from smaller particle size of polymer. The results of this study also showed that compaction force has greatly affected drug release rate from EC matrices. Increasing the compaction force increased the crushing strength of matrices and subsequently the rate of drug release decreased. In all matriecs the main mechanism controlling drug release rate was found to be erosin.

Background: Thiopentone is one of the most frequently used drugs for induction of anesthesia. Concerning to it's induced hemodynamic changes, especially in patient's with IHD and hypertension, we did this research to evaluate the decrement in E050 and find an effective dose of pre-induction Anesthesia to reduce the amount of thiopentone. Method: 96 adult patient (class AsAI) have been studied by single blind method. Changes of thiopentone ED50 in relation to pre-inductional fentanyl was determined. These findings was compared to control group. Results: Based on these findings fentanyl in doses of 2.5 µg/kg or more, can produce a clear decreased in ED50 of thiopentone. This would be so beneficial cardiovascular patients. in stability of hemodynamic state of Conclusion: To avoid the adverse effects of thiopentone especially in highdoses. It will be better to decrease the induction dose of drug by using the pre-induction of fentanyl.

Nowadays thera are a lot of reports on literature about modern techniques to change the bitter taste of chewable adults and children cold tablets, and methods of evaluating these products, such as: wet granulation and solid dispersion. By using solid dispersion method, chewable tablets were made with a sweet taste, and all physical experiments on tablets were carried out The suggested tablets were compared with some Persian made tablets, via some taste evolution method. In comparison it becomes clear that the bitter taste of the suggested tablets changed noticialaly.

Naproxen (NP) a potent non-steroidal anti inflammatory drug is used in most musculoskeletal disorders such as rheumatoid arthritis. Since NP can damage the mucous of gastrointestinal tract, suppository dosage form can be useful in circumventing this side effect. In this research NP suppositories were formulated using different oleogineous and water soluble bases. After performing different physicochemical controls, the dissolution studies were accomplished. The time for the release of total drug from suppositories were 180 and 200 minutes for oleoginous and water soluble bases respectively. To optimize the release rate of drug from suppositories, different surfactants, (nonionic, anionic and cationic), were included in bases in concentration of 0.5% and 1% w/w. the results showed that Tween 80 (0.5%w/w) in witepsol H.15 base and cetyl pyridinium chloride (0.5%w/w) in witepsol W35 caused the decrease in time for total release of drug respectively to 45 and 60 minutes, However, non of surfactants had pronounced effect on the release of drug from the water soluble bases.

There is much evidence indicating that the serotonergic system involves in the central regulation of nociceptive sensitivity. Several drugs are able to produce analgesic effect through serotonin re uptake inhibition or effect on it's receptors. Studies show that antidepressants such as desipramine, amitriptyline, clomipramine, citalopram and zimelidine have analgesic effect in experimental pain models; however, there isn't any report concerning analgesic effect of chronic and acute administered fluoxetine. The aim of this study was to investigate the effect of chronic and acute injected fluoxetine on hot plate test. Results of this study showed that chronic (0.16, 0.2 and 0.24 mg/kg, i.p. for 5 days) and acute (0.2 and 0.24 mg/kg, i.p.) administration of fluoxetine, as a serotonin re uptake inhibitor, produced significant analgesia. Fluoxetine (0.24 mg/kg, i.p.) increased analgesic effect of morphine (1 mg/kg, i.p.) significantly. Furthermore, analgesic effect of fluoxetine (0.24 mg/kg, i.p. and 0.24 mg/kg, i.p., for 5 days) was reversed by naloxone (2 mg/kg, i.p.). Results obtained from this study showe that chronic and acute injection of fluoxetine induce analgesic effect on hot plate test through activation of opioidergic neurons. The exact mechanism of interaction between serotonergic and opioidergic system is not clear and remains to be elucidated.