Iranian Journal of Pharmaceutical Research
Volume:2 Issue: 3, Summer 2003

Achieving a desirable percutaneous absorption of drug molecule is a major concern in formulating dermatological products. The use of penetration enhancers could provide a successful mean for this purpose. The aim of this study was to evaluate the effect of incorporating a few common penetration enhancers (in different concentrations) into a 0.5% w/w piroxicam (model drug) gel formulation, on the permeability rate of drug through rat abdominal skin in vitro. For this purpose various concentrations of oleic acid (OA), urea (UR), lecithin (LEC) and isopropyl myristate (IPM) were used as the penetration enhancer. In order to investigate the effect of penetration enhancers used in this study on the permeability rate of piroxicam through sections of excised rat skin, Franz-type diffusion cells were employed. The receptor phase was constantly stirring 0.9% w/v sodium chloride solution at 32°C. At set intervals up to 8h, 5ml samples were removed from the receptor compartment and the amount of piroxicam permeated through the skin calculated by determining the UV absorbance of drug at 353 nm. Results show that among the penetration enhancers used, the use of OA at a concentration of 1.0% w/w had the greatest effect on the permeability rate of piroxicam, and produced the highest enhancement ratio among all the penetration enhancers examined. The other penetration enhancers used were found to have a far smaller effect on the permeability rate of piroxicam through rat skin. The enhancement ratio of the penetration enhancers used in the formulation of piroxicam gel were found to increase in the order of OA>> IPM > LEC > UR

Deproteinisation with acetonitrile (along with methanol or other reagents) is a useful and rapid technique in analysis of drugs or their metabolites in human serum. In this paper application of this simple technique in biopharmaceutical analysis using capillary electrophoresis (CE) is evaluated. Some drugs with different ionic and protein binding properties were selected and dissolved in human serum. The efficiency of deproteinisation of spiked serum samples with acetonitrile and further analysis with CE was evaluated for each sample with special interest on the neutral drugs. The results showed that deproteinisation method is more efficient for charged molecules with low protein bindings. For neutral, relatively non-polar compounds (such as praziquantel), a MEKC method is preferred. For neutral, highly polar molecules (such as methimazole) other means of sample preparation must be considered.

Many properties of chemicals depend on their streochemistry. Among these, the effects of streoisomerism on percutaneous absorption of drugs, which is subject of the present investigation, is not well studied yet.In this study, tretinoin (TT) and isotretinoin (ITT) (geometric isomers) were chosen and their permeations (alone or in the presence of each other) through enhancer-treated excised rat skin were studied. These studies employed static diffusion cells, saturated solution of drugs in water:propylene glycol system as the donor phase and aqueous solution of Tween20 as the receptor phase. Aqueous solutions of sodium dodecyl sulfate (SDS) (2, 4, 6 and 8%, w/v) and ethanol (EtOH) (25, 50, 75 and 96%, v/v) were used as enhancers.Results showed that TT permeates SDS-treated skin by about 1.6-1.8 times faster than ITT (P<0.0001). Permeability coefficient (Kp) of TT through SDS-treated skin was also 1.1-1.3 times more than that of ITT (P<0.004). In ethanol-treated systems, while the flux of TT was significantly (P<0.0003) more than that of ITT (by about 1.4-1.7 times) for all ethanol concentrations, there was no difference between Kp of TT and ITT in 25 and 50% ethanol-treated systems. At higher ethanol concentrations, Kp of TT was significantly (P<0.046) more than that of ITT. When the retinoids were used together, flux ratios (TT/ITT) were almost twice of those observed in single-retinoid application studies. These data show that the isomers might affect permeation of each other, which might be due to competition of isomers for permeation through the skin.The present results clearly show that permeation of these isomers through enhancer-treated rat skin is stereoselective, and that the level of stereoselectivity depends on enhancer type and concentration.

Acebutolol (AC) is a chiral b-adrenergic blocking drug, which is useful clinically as the racemate in treating hypertension and is metabolized to an equipotent chiral metabolite, diacetolol (DC). In this paper we report a case of a 32 year old woman who was receiving AC during her pregnancy and lactating time for management of hypertension. The maternal plasma level and breast milk as well as cord blood collected to see whether the drug is transferred to the fetus through the mother stereoselectively. A stereospecific high-performance liquid chromatographic (HPLC) assay was used to measure the enantiomeric concentrations of AC and DC. AC and DC enantiomers are stereoselectively excreted into the milk, although the concentrations of DC enantiomers were higher than those of AC. AC concentrations were very low in both cord artery and vein samples four hours after taking the drug however, the stereoselective concentrations of metabolite, DC, was found in these samples. In conclusion, AC and DC enantiomers are excreted in human breast milk in concentrations much higher than that in maternal plasma. Furthermore, DC was found in the infant’s plasma indicating that accumulation of metabolite did occur in this infant.

This article describes a simple and fast high-performance liquid chromatography method for the determination of methotrexate (MTX) in plasma. Samples were collocted from children receiving high-dose MTX at shafa Hospital (Ahvaz University of Medical sciences, Ahvaz, iran) at various times after the end of eachinfusion. Plasma was deproteinized with trichloroacetic acid and the supernatant was injected into a 250×4.6 mm octadecylsilane column. Mobile phase was made of TRIS-phosphate buffer (pH 5.7): methanol: acetonitrile (82:11:7) with a flow rate of 1.8 ml/min. Ultraviolet detection was done at 313 nm and at ambient temperature. Para-aminoacetophenone was used as internal standard. Methotrexate and internal standard retention times were 4.4 and 6.5 minutes, respectively. Results showed that reproducibility (precision) of method within a day was 2.6 to 6 percent and between days was 5.5 to 9.5 percent. The recovery of the method was between 61.5 and 72.7 percent. The quantitation limit of the method for methotrexate was 0.1 µM. This method is suitable for quantitation of methotrexate after infusion of high doses of this drug and has good accuracy, precision and quantiatation limit.

The relative bioavailability of the test (generic) product 2 × 25 mg baclofen tablets, with respect to the reference product, Lioresal® 2 × 25 mg tablets (baclofen; Squibb) was determined in a single-blind, single dose, randomised, crossover study. The mean values for the variable Cmax were 737.6 ng/ml for the reference and 739.5 ng/ml for the test product. The mean values for the variable AUC were 3980.3 hr.ng/ml and 4066.7 ng.hr/ml for the reference and test, respectively. The 90% confidence intervals for the "test/reference" mean ratios of the plasma baclofen pharmacokinetic variables Cmax and AUC0-t (as measures of the rate and extent of absorption of baclofen, respectively) lie between 0.98 and 1.06, which is within the conventional bioequivalence range of 80-125%. The test product (baclofen) is therefore bioequivalent to the reference product (Lioresal®) with respect to the rate and the extent of absorption of baclofen with a strength of 25 mg.

Ophthalmia neonatorum is generally defined as conjunctivitis occurring within one month of life. The sources of this infection are environmental organisms or the organisms colonized in the birth canal. Untreated infection can cause blindness, especially if the corresponding organisms areNeisseria gonorrhoeae, or Chlamydia trachomatis.Povidone-iodine ophthalmic solution is an effective antibacterial agent with broad antibacterial and antiviral activity to which no bacterial resistance has been known. It is less expensive and less toxic than the agents currently used to prevent neonatal conjunctivitis. It turns the conjunctiva brown for a few minutes, a characteristic that can serve as an indicator of being properly applied. Because this preparation is not available in Iran, its formulation can be valuable.In this study, the povidone-iodine ophthalmic solution was prepared in concentration of 2.5%, and then required control parameters such as pH, self-preservation effect, tonicity, sterility, and chemical stability were studied. In this clinical study, one drop of povidone-iodine ophthalmic solution was instilled in each eye of 475 neonates within 30 minutes of birth.This study demonstrated that povidone-iodine in concentration of 2.5% is self-preservative against microbial contamination. The pH of solution was adjusted about 5 near to the pH of tear using sodium hydroxide 0.1 N and citric acid 0.5%, because in this pH povidone-iodine was more stable. Tonicity was measured according to an in vitro hemolytic method. Povidone-iodine 2.5% solution was packaged in amber color bottles, and after ensuring from its sterility, it was used in clinical study. Among the population studied, eye discharge was observed in 2.94 percent in comparison to the control group in which eye discharge was observed in 10.9 percent.In conclusion because of availability, low cast, and good clinical results, a 2.5% ophthalmic solution of povidone-iodine is desirable to use as a prophylactic agent against ophthalmia neonatorum.

Combination formulations of liposomes with collagen have been previously introduced as a means of obtaining more stable and less permeable liposomes. In this study, the effect of aqueous solutions of the collagen products COLLAPURÒ (COL) and COLLAPURON-DAKÒ (COLD) from Henkle Co., on the release rate of sodium chromate (CHR) as a water-soluble model drug from stable plurilamellar vesicles (SPLVs) was evaluated. Results showed that dispersing SPLVs in diluted solutions (10%) of the collagens, increased the release rate from liposomes at 32°C. It is speculated that after binding to the hydrophilic surface of liposomes, the structure of the collagen changes and the hydrophobic portions become more exposed. This is likely to cause a penetration of these portions into the bilayer structure (which is fluid at this temperature), thus causing an expansion in the membrane and an increase in permeability. In higher concentrations (30% and 50%), this increasing effect is not observed, which is suggested to be due to the aggregation of collagen fibrils and the resultant higher viscosity. It is concluded that these collagens in optimum concentrations could find a good place in the preparation of topical liposomes, due to their flexible effects on the release rate of liposomes, as well as the dermatological effects of collagen itself.

L-tyrosine, B6 and folic acid are involved in biosynthesis of DOPA and consequently dopamine. The aim of this study was to investigate the antiparkinsonian effect of these agents in perphenazine-induced catatonia in rats. Murprogo method or scored muscular rigidity, which is induced by a phenothiazine, was used to evaluate the antiparkinsonian effect of these agents. A significant decrease in muscular rigidity was observed in groups that received L-tyrosine. However, groups which had received vitamin(s) only showed no significant decrease in muscular rigidity as compared with the control group. On the other hand, the group receiving folic acid plus L-tyrosine showed a lower degree of muscular rigidity in comparison with the other groups.In conclusion, L-tyrosine has been found to be effective in improving perphenazine-induced muscular rigidity. Furthermore, when used in combination with folic acid, L-tyrosine could be found advantageous in the early stages of Parkinson’s disease.

The Pyrrolizidine Alkaloids (PAs) are a group of chemicals found in a variety of plant species throughout the world. These toxic alkaloids are distributed mainly in Senecio (Compositae), Crotalaria (Legominosae) and Heliotropium (Boraginaceae) species. Plants containing these alkaloids cause significant mammalian morbidity and mortality, especially in humans. Upon ingestion, metabolic activation in liver converts the potent compounds into highly reactive electrophiles capable of reacting with cellular macromolecules forming adducts, which can initiate acute or chronic toxicity.One of these plants is Senecio vulgaris which is abundant in wheat farms of Mazandaran province. When wheat (Triticum spp) is being harvested, seeds and aerial parts of Senecio would also be collected with it. Since the presence of PAs in Senecio vulgaris is proven in a previous research, hence in this study, quality and quantity of PAs of wheat and flour contaminated with Senecio in Mazandaran province farms have been studied.The specimens were collected from all flour industries four teen sites and silo of Mazandaran. The Ehrlich reaction test and spectrophotometeric method were used for the qualitative and quanlitative examinations, respectively. The Amount of PAs and their N-oxides calculated on the basis of senecionine. The reaction is specific for alkaloids having an unsaturated basic moiety ofΔ3– pyrroline ring. In the qualitative test, the existence of PAs was demonstrated in all specimens. Mean amount of the total PAs and their N-oxides in 0.512g of specimens was 0.020 to 0.05 mg (as senecionine). Total PAs in 0.512g of Senecio vulgaris was 0.4mg.LD50 of senecionine, fatal toxic dose of PAs and nonfatal toxic dose of PAs are 64.72 ± 2.24 mg/kg, 6–167 mg/kg, and 2–27 mg/kg, respectively. Comparing the amount of PAs in wheat and its flour as well as its toxic dose, the specimens would not scem to produce acute complications of Pas. However, long term exposure to low levels of PAs may cause cumulative damage especially hepatotoxicity. Meanwhile chronic toxicity to humans by diet, including the specimens, is possible.

The hydrodistilled oil of the aerial parts of Echiophora platyloba DC. was analyzed by GC and GC/MS. Ten components have been identified, of which the major constituents were found to be trans-b -ocimene (67.9%), 2-furanone (6.2%), myrcene (6.0%), linalool (3.1%), and cis-b -ocimene (2.3%).

The role of antioxidants in prevention and treatment of cancers have been reported by several studies. In our investigation we studied the effects of ascorbic acid, α-tocopherol, and sodium selenite on proliferation of two breast cancer cell lines: T47D (estrogen-receptor positive) and MDA-MB-231 (estrogen-receptor negative). We also used 17-β-estradiol as positive control for proliferation of T47D cells. The viability of cells after 7 days of exposure to different concentrations of test compounds was determined by resazurine based method. Ascorbic acid and α-tocopherol significantly inhibited cell growth at a concentration of 10-4 M in both cell lines and antagonized the cell proliferation induced by 17-β-estradiol in T47D cells. Sodium selenite at concentrations above 10-6M strongly inhibited the cell growth in both cell lines and suppressed the stimulated growth of T47D cells by 17-β-estradiol. Our results with different strengths of activity of test compounds, further confirmed the findings of previous studies that showed the inhibitory effects of these antioxidants on other malignant cell lines.