Iranian Journal of Pharmaceutical Sciences
Volume:3 Issue: 1, Winter 2007

Megaloporous controlled release tablets of diclofenac sodium (DS) were prepared with two kinds of granules. One of them is the restraining-phase matrix granule (RMG) and it controls the release rate of the drug. The other one is the soluble housing-phase matrix granule (HMG) and controls liquid penetration into the system. Carnauba wax and Eudragit L 100 polymers were used to constitute the restraining and housing matrix phases, respectively. The prepared tablets were evaluated for various parameters. In vitro drug release study was carried out in simulated gastric fluid (pH 1.2) for the first 2 h and in phosphate buffer (pH 7.2) for the next 10 h following USP 25 paddle method. Two independent model methods, AUC and Lin Ju and Liaw's difference factor (ƒ1) and similarity factor (ƒ2) were used to compare various dissolution profiles. The fabricated megaloporous matrix tablets released only 3 to 5% of DS in pH 1.2 depending on the proportion of carnauba wax used in the RMG. Increase in polymer content/hardness value of the tablet resulted in a significant decrease in AUC0-2 h and AUC2-12 h values . The f1and f2analysis also confirms the discrimination between corresponding dissolutionpairs. The dissolution profiles of an ideal matrix formulation containing 15.77% carnauba wax and 6.76% Eudragit L100 was found to be comparable with the reference product (Voveran® SR) and theoretical release profile. The drug release from all fabricated products and reference product followed better Higuchi model than the zero order and first order kinetic models. Ritger-Peppas model analysis indicated that the DS release followed non-Fickian transport mechanism. From the above analysis, it is evident that the release mechanism of DS from matrix tablet is influenced by both hardness and polymer contents. The stability profiles indicate that the physico-chemical properties of the tablets are not affected on storage at 45°C /75% RH up to 6 months.

The aim of this study was to use site directed mutagenesis technique to construct a vector in which serine363 and serine375 residues of the COOH-terminal portion of the μ-opioid receptor (MOR) were substituted by alanine. These constructs are essential in studying G-protein coupled receptor kinase-mediated MOR desensiti-zation. The nested PCR carried out for conversion of serine363 and serine375 to alanine resulted in the production of a band comparable to the expected size of 1400 bp. Restriction analysis of these bands confirmed the integrity of the PCR products. Ligation of the mutated PCR product into pcDNA3 and its digestion with appropriate restriction enzymes further confirmed the integrity of the PCR product and its orientation into the vector.

Carnitine is a vital biologic substance for transporting fatty acids into myocytes. It also facilitates fatty acids β-oxidation for energy production. In this study, effects of L-carnitine (L-Car) on apoptosis in the ischemic isolated rat heart were investigated. Male Sprague-Dawley rats were divided into four groups and anesthetized by sodium pentobarbital. The heart was removed and mounted on a Langendorff apparatus then perfused by a modified Krebs-Henseleit (K/H) solution under a constant pressure at 37 °C. In the control group, the hearts were perfused only by normal K/H solution at stabilization, 30 min. regional ischemia and 120 min. reperfusion, while in each of the test groups, the hearts were perfused during ischemia-reperfusion with 0.5, 2.5 and 5 mM of L-Car-enriched K/H solution, respectively. At the end of reperfusion, immunohistochemical detection of apoptotic cells was performed by using an in situ apoptosis detection kit. The number of TUNEL-positive cardiomyocytes was counted in five random high-power fields in each sample. In the control group, the number of apoptotic cells were 48±3 while addition of L-Car (0.5, 2.5 and 5 mM) to the solution reduced the number of apoptotic cells to 6±1, 4±1 and 3±1, respectively (p

Gamma-aminobutyric acid (GABA) is an important inhibitory transmitter in central nervous system and is involved in pathophysiology of epilepsy. Pentylenete-trazole (PTZ), a convulsant agent, partly acts via anion channel of GABAA receptor. Ivermectin, an antiparasitic agent and a GABAA agonist, has anticonvulsant effect in animal seizure models. Cholestasis increases the threshold of PTZ-induced clonic seizure in mice. The object of this study was to clarify the involvement of GABAergic pathways in increasing PTZ-induced seizure threshold (ST) in cholestatic mice. The result of this study showed that cholestasis increases clonic ST three days after surgery while sham-operated control (SOC) and unoperated control (UOC) groups did not show any alteration in clonic ST. Bicuculline, a GABAA antagonist, reversed but ivermectin increased the clonic ST in UOC, SOC and bile duct-ligated mice, respectively. In conclusion, our results showed that: (1) acute cholestasis is associated with an increase in PTZ-induced clonic ST in mice and this phenomenon may be the result of reinforcement of GABAergic system, and (2) GABA plays a physiological role in regulation of ST.

The aim of the present research was to study the effects of weak cation exchange resins, polacrilex with exchangeable H+ and polacrillin potassium and strong cation exchange resin sodium polystyrene sulfonate on water uptake behavior of ranitidine hydrochloride. Drug resin complexes (DRC) were prepared and evaluated for the percentage of moisture gain when placed in a humidity chamber at 40E2 °C and 75E5% RH for 17 h as compared to drug and free resins under the same condition. Equilibrium moisture content (EMC) under different humidity conditions and the rate and extent of moisture uptake in the presence (15 watt florescence light) and absence of light under 40E2 °C and 75E5% RH were also calculated for DRCs, drug and unloaded resins. DRC 264 (containing polacrilex with H+) gained minimum weight (10.22%) maintaining free flowing characteristics whereas other resinates showed higher weight gain and formation of sticky mass while ranitidine HCl turned liquid with gain of 28.11% weight. The rate of moisture uptake by ranitidine HCl was found to increase in the presence of light with slight difference in extent, whereas moisture uptake rate was independent of light in the case of resins. Even though DRC 264 contained ranitidine HCl, the moisture uptake rate was unaffected by light and saturation in moisture gain was seen just at 6 h. Thus, loading ranitidine HCl on polacrilex resin with exchangeable H+ significantly improves its moisture resistance and may not require very tight environmental controls during its formulation.

A simple, reproducible and rapid gas chromatographic method for precise determination of valproic acid (VPA) in human plasma has been developed. Total time for sample preparation and GC analysis is less than 45 min. After plasma protein precipitation, VPA was extracted into chloroform with suitable recovery. By using Stabilwax®-DA capillary GC column, a symmetrical gas chromatographic peak was obtained without the need for derivatization. The calibration curve was proved to be linear (r2 = 0.998) in a wide concentration range (0.45-100 μg/ml). Inter-day and intra-day accuracy and precision of this method was investigated during the method validation and the method has good precision and accuracy. This method is highly reproducible with a limit of detection 150 ng/ml of VPA in human plasma and could be used in TDM and pharmacokinetic studies.

A simple and sensitive extractive spectrophotometric method is described for determination of tropicamide. The method is based on the reaction of tropicamide and bromocresol green. The ion-paired colored complex was extracted with chloroform at pH 3. The extracted complex showed maximum absorbance at 423 nm. The complex was stable up to 2 days and obeyed Beer's law over the concentration ranges of 1.32-100.81 μg/ml. No significant interference was observed from the excipients, coloring and flavoring agents commonly used in the tropicamide pharmaceutical preparations. The proposed method was applied successfully for determination of tropicamide in commercial eye drop dosage forms.

Licorice is obtained from Glycyrrhiza glabra (G. glabra) in Iran. Glycyrrhizin is the main constituent of G. glabra and has several pharmacological effects. It is hydrolyzed to glycyrrhetic acid (GA) in the intestine after oral administration. In this study, a novel HPLC method was used to determine the concentration of GA in rat plasma after oral administration of licorice aqueous extract. The method was linear (r2 >0.999) in the range of 0.1-5.0 μg/ml for GA. Maximum plasma concentration of GA was achieved 8 h after oral administration of licorice aqueous extract. The developed method was suitable for determination of GA in rat plasma.