Iranian Journal of Pharmaceutical Research
Volume:2 Issue: 4, Autumn 2003

In order to formulate an efficient and durable mucoadhesive drug delivery system, careful consideration of formulation-related parameters is critical. This study was conducted to investigate the effect of the presence of various types and concentrations of surfactants within or outside Carbopol 934 (C934) as well as hydroxypropylmethyl cellulose (HPMC) solid compacts, on their duration of mucoadhesion in vitro. Surfactants used in this study were chlorhexidine (CLH, cationic), sodium lauryl sulfate (SLS, anionic), and Poloxamer 407 (POL407, nonionic). These surfactants were individually dissolved in pH 7.0 phosphate buffer or added inside the solid compacts, and their effects on the duration of mucoadhesion of C934 and HPMC solid compacts determined at 37ºC, using rat small intestine as the model membrane. Results showed that the presence of CLH outside both C934 and HPMC compacts produces the greatest reduction in their duration of mucoadhesion among the three types of surfactants studied. Effect of the other two investigated surfactants, on reducing the duration of mucoadhesion of C934 and HPMC solid compacts was exceedingly less than that of CLH. For C934 compacts, the effect of SLS was to some extent more than POL407. However, the reverse was observed with HPMC compacts. With all the different types of surfactants investigated, increasing the concentration of surfactant resulted in a greater reduction in the duration of mucoadhesion of solid compacts. Furthermore, HPMC compacts were generally found to be more sensitive to the presence of various types and concentrations of surfactants within the external buffer medium. In fact the presence of CLH at a concentration of 0.2%, within the buffer medium, completely prevented their adhesion to the mucosal surfaces. In conclusion, the presence of all three types of surfactants studied within C934 solid compacts reduced the duration of mucoadhesion greatly less than their presence within the buffer medium. This trend was also observed for HPMC compacts containing CLH and POL407. However, the presence of SLS (at concentrations above 0.5%) within HPMC compacts managed to reduce their duration of mucoadhesion more than when present in the outer buffer medium.

A sustained-release tablet formulation should ideally have a proper release profile insensitive to moderate changes in tablet hardness that is usually encountered in manufacturing. In this study, matrix aspirin (acetylsalicylic acid) tablets with ethylcellulose (EC), Eudragit RS100 (RS), and Eudragit S100 (S) were prepared by direct compression. The release behaviors were then studied in two counterpart series of tablets with hardness difference of three Kp units, and compared by non-linear regression analysis. The release pattern for both the S-containing and RS-containing formulations fitted best in Higuchi model, and the proper equations were suggested. In the EC-containing formulation, Higuchi and also zero-order models were probable models for the release, and a combination equation for the release was suggested. In the S-containing formulation, the release profile was completely sensitive to the hardness change. In RS-containing series, the slope of the release graph did not change due to the hardness decrease, but the y-intercept or the lag time in release was decreased. In EC-containing matrix tablets, both the slopes and the y-intercepts did not change by the decrease in hardness. In conclusion, EC with an amount as little as 10 percent in formulation could make sustained-release aspirin tablets in which the release profile is not sensitive to moderate changes in hardness.

Iron, cobalt and copper are metals, which appear together in many real samples, both natural and artificial. Recently a classical univariate micellar colorimetric method has been developed for determination of these metal ions.The organized molecular assemblies such as micelles are used in spectroscopic measurements due to their possible effects on the systems of interest. The ability of micellar systems to solublize slightly insoluble or even very insoluble complexes and/or ligands has been used to enhance the analytical merit of the given methods. The ability of micelles to solublize complexes in aqueous solutions can eliminate the need for non-aqueous extraction step in a given analysis.The simultaneous determination of Fe, Co and Cu was carried out as 1-nitroso-2-naphtol complexes in presence of aqueous solution of nonionic surfactant of Triton-X100. A partial least-squares multivariate calibration method for the analysis of ternary mixtures of Fe, Co and Cu was developed. For individual determinations, molar absorptivities and the limit of detection were obtained, respectively. The total relative standard error for applying the method on synthetic samples was 2.02%. The proposed method was also successfully when applied to the determination of Fe, Co and Cu in several synthetic alloy solutions.

The bioavailability of two dipyridamol tablet formulations of (Dipyridamole from Tolidaru and Persantin from Boehringer) was compared in 14 healthy male volunteers who received a single dose of 25 mg of the test (T) and the reference (R) products in a randomized balanced 2-way crossover design. Plasma samples were obtained over a 16 h interval and dipyridamole concentrations determined by HPLC with ultraviolet detection. The maximum plasma concentration (Cmax), area under the plasma concentration time curve up to the last measurable concentration (AUC0-t), as well as infinity (AUC0-¥), and the absorption rate (Cmax/AUC0-¥) were analyzed statistically under the assumption of a multiplicative model. The time to maximum concentration (Tmax) was analyzed assuming an additive model. The parametric confidence intervals (90%) of the mean values of the pharmacokinetic characteristics for T/R ratio were in each case well within the bioequivalence acceptable range of 80-125%. The test formulation was found bioequivalent to the reference formulation by the Schuirmann’s two one-sided t tests and by Wilcoxon Mann Whitney two one-sided tests procedure. Therefore, the 2 formulations were considered to be equivalent

In the present study, interactive effects of D1 and D2 dopamine receptors antagonists and different periods of lithium pretreatment on morphine dependence in mice have been investigated. This study was designed to investigate whether the hypothesis that lithium and dopaminergic mechanisms via their effects on phosphoinositide pathways and calcium flux could influence morphine withdrawal response as manifested in the jumping effect. Animals were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily (10 a.m., 1 p.m. and 4 p.m.) for 3 days, and a last dose of morphine (50 mg/kg) was administered on the 4th day. Withdrawal syndrome (jumping) was precipitated by naloxone (5 mg/kg) which was administered intraperitoneally 2h after the last dose of morphine. To study interactive effects of dopamine receptor antagonists and different duration of lithium pretreatment, 10 injection of morphine (3 administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. SCH 23390 (0.01, 0.02 and 0.05 mg/kg) as a D1 dopamine receptor antagonist and sulpiride (20, 40 and 80 mg/kg) as a D2 dopamine receptor antagonist were able to prevent withdrawal signs precipitated by naloxone (5 mg/kg). Pretreatment of animals with lithium (600 mg/l) for 7, 14, 21 and 28 days, increased jumping induced by naloxone in morphine dependent animals. SCH 23390 did not show any significant alteration on the jumping response in animals pretreated with lithium for 28 days, but the inhibitory effects of sulpiride was significantly decreased in animals received lithium for 28 days. It is concluded that postreceptor mechanism (s) may be involve in the interactions of lithium with dopaminergic system in alteration of naloxone-induced jumping in morphine dependent animals.

There are several conflicting evidences showing the effect of morphine on learning and memory processes. In the present study the effect of chronic morphine administration on passive avoidance, active avoidance and spatial learning and memory of morphine dependent male rats using Passive Avoidance shuttle box and Morris Water Maze tasks were investigated, respectively. Male rats received morphine sulfate in their drinking water for 21 days. Morphine dependency was assessed by injection of naloxone HCl (2 mg/kg) showing the withdrawal signs. Our results showed that in the passive avoidance experiments although the learning of the morphine dependent group was lower than the sham and control groups, but was not statistically significant. Also no significant difference was observed between the memory retention of these groups. In the 2-way active avoidance task, learning was increased significantly in morphine dependent rats in the first day of training with respect to the sham and control groups. But, there was no significant difference in memory of these three groups. Our data in the Morris Water Maze showed that learning of the dependent group in the 3rd day of training decreased significantly with respect to the sham and control groups. But no significant difference was observed in their memory retention and also in their motor activity. Our results showed that in the male rats, chronic morphine administration decreased spatial learning, but had no effect on spatial memory and motor activity. On the contrary, it facilitated 2-way active avoidance learning but had no effect on active and passive avoidance memory. In conclusion, it seems that the effect of morphine dependency on learning and memory in rats is task dependent and depends on the types of experimental learning and memory paradigms.

Several therapeutic effects including hypnotic, antispasmodic, treatment of abdominal and chest pain and strengthening the heart have been described for the flowers of Rosa damascena. North American Indian tribes use a decoction of the roots obtained from the Rosa damascena plant as a cough remedy and to treat eye problem. Therefore, in the present study the antitussive effect of this plant in guinea pigs was evaluated. The antitussive effect of aerosols of two differ­ent concentrations of ethanolic extract (5 and10% w/v), aqueous extract (10 and 20% w/v), codeine, and saline were tested counting the number of cough produced due to aerosol of citric acid 10 min after exposing animal to aerosols of different solutions (n=6 for each solution). The results showed a significant reduction in the number of coughs obtained in the presence of both concentrations of ethanolic extract, higher concentrations of aqueous extract and codeine (P<0.001 for all cases). The number of coughs obtained in the presence of higher concentrations of extract was less than that of lower concentrations. However, this difference was only statisti­cally significant for the aqueous extract. In addition the numbers of coughs obtained in the presence of both concentrations of ethanolic extract and higher concentrations of aqueous extract were not significantly different from that of codeine. These results indicated the antitussive effect of Rosa damascena, which was comparable to codeine at concentrations used.

The antioxidant activity of the different extracts and fractions of aerial parts of Otostegia persica (Burm.) Boiss. were evaluated using beta-carotene bleaching and lipid peroxidation methods. The inhibitory activity of the plant extracts on the peroxidation of linoleic acid were measured by ferric thiocyanate method in comparison to methanolic extracts of Green tee, Ginkgo biloba, Vit.E and BHA as positive controls. Methanolic extract of the plant exhibited strong antioxidant activity. Two compounds of methanolic extract which were separated by column and paper chromatography showed significant antioxidant activity comparable to butylated hydroxy anisole (BHA) and alpha tocopherol. These active compounds were identified as morin and quercetin by using UV, IR, MS, ¹H and ¹³C NMR.

volatile constituents of the aerial parts of Varthemia. persica DC. var. persica, growing wild in Iran, were investigated by GC-MS. Sixty seven constituents were identified. δ-Cadinene (9.7%), Selin-11-en-4-α-ol (5.30%), Germacrene D (4.9%), Bicyclogermacrene (4.7%), α‑Muurolene (4.7%), β-Eudesmol (4.52%), β-Himachalen oxide (3.6%), γ-Eudesmol (3.54%), β-Bourbonene (3.21%) were found to be the major constituents of the oil respectively.

The essential oil of the root of Heracleum persicum (Apiaceae) was analyzed by capillary GC and GC /MS. The major constituents were identified as viridiflorol (23.05 %), elemol (3.63 %), b-maliene (3.07 %), spathulenol (3.34 %) and 2-tetradecanol (3.38 %).

From the aerial parts of Tanacetum balsamita L. (Compositae) a flavonol aglycon was iso­lated using chromatographic techniques. The structure of this compound was determined using spectroscopic methods (UV, H-NMR and MS) as 3'',4'',5,7-Tetrahydroxy flavonol (Quercetin).

A flavonol, kaempferol, isolated from the fresh flower petals of C. sativus L. (Iridaceae) as the sole component. The structure of the compound was determined by chemical and spectroscopic methods