Iranian Journal of Pharmaceutical Sciences

Megaloporous controlled release tablets of diclofenac sodium (DS) were preparedwith 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 solublehousing-phase matrix granule (HMG) and controls liquid penetration into thesystem. Carnauba wax and Eudragit L100 polymers were used to constitute therestraining and housing matrix phases, respectively. The prepared tablets wereevaluated for various parameters. In vitrodrug release study was carried out insimulated gastric fluid (pH 1.2) for the first 2 h and in phosphate buffer (pH 7.2)for the next 10 h following USP25 paddle method. Two independent modelmethods, AUC and Lin Ju and Liaw's difference factor (ƒ1) and similarity factor (ƒ2)were used to compare various dissolution profiles. The fabricated megaloporousmatrix tablets released only 3 to 5% of DS in pH 1.2 depending on the proportionof carnauba wax used in the RMG. Increase in polymer content/hardness value ofthe tablet resulted in a significant decrease in AUC0-2h and AUC2-12h values . Thef1and 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 thereference product (Voveran®SR) and theoretical release profile. The drug releasefrom all fabricated products and reference product followed better Higuchi modelthan the zero order and first order kinetic models. Ritger-Peppas model analysisindicated that the DS release followed non-Fickian transport mechanism. From theabove analysis, it is evident that the release mechanism of DS from matrix tabletis influenced by both hardness and polymer contents. The stability profiles indicatethat 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 constructa vector in which serine363and serine375residues of the COOH-terminal portion ofthe μ-opioid receptor (MOR) were substituted by alanine. These constructs areessential in studying G-protein coupled receptor kinase-mediated MOR desensiti-zation. The nested PCR carried out for conversion of serine363and serine375to alanineresulted 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 appropriaterestriction enzymes further confirmed the integrity of the PCR product and itsorientation 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, effectsof 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 bysodium pentobarbital. The heart was removed and mounted on a Langendorffapparatus then perfused by a modified Krebs-Henseleit (K/H) solution under aconstant pressure at 37 °C. In the control group, the hearts were perfused only bynormal K/H solution at stabilization, 30 min. regional ischemia and 120 min.reperfusion, while in each of the test groups, the hearts were perfused duringischemia-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 apoptoticcells was performed by using an in situapoptosis detection kit. The number ofTUNEL-positive cardiomyocytes was counted in five random high-power fields ineach sample. In the control group, the number of apoptotic cells were 48±3 whileaddition of L-Car (0.5, 2.5 and 5 mM) to the solution reduced the number ofapoptotic cells to 6±1, 4±1 and 3±1, respectively (p<0.001 for all concentrations).There was no significant difference between and within test groups using ANOVAone-way. Considering these results, we conclude that L-Car has a protective effectagainst cardiac ischemia-reperfusion induced injuries as a reduction of apoptoticcardiomyocytes.

Gamma-aminobutyric acid (GABA) is an important inhibitory transmitter incentral nervous system and is involved in pathophysiology of epilepsy. Pentylenete-trazole (PTZ), a convulsant agent, partly acts via anion channel of GABAAreceptor.Ivermectin, an antiparasitic agent and a GABAAagonist, has anticonvulsant effectin animal seizure models. Cholestasis increases the threshold of PTZ-inducedclonic seizure in mice. The object of this study was to clarify the involvement ofGABAergic pathways in increasing PTZ-induced seizure threshold (ST) in cholestaticmice. The result of this study showed that cholestasis increases clonic STthree daysafter surgery while sham-operated control (SOC) and unoperated control (UOC)groups did not show any alteration in clonic ST. Bicuculline, a GABAAantagonist,reversed but ivermectin increased the clonic STin UOC, SOC and bile duct-ligatedmice, respectively. In conclusion, our results showed that: (1) acute cholestasis isassociated with an increase in PTZ-induced clonic STin mice and this phenomenonmay be the result of reinforcement of GABAergic system, and (2) GABAplays aphysiological role in regulation of ST.

The aim of the present research was to study the effects of weak cation exchangeresins, polacrilex with exchangeable H+and polacrillin potassium and strong cationexchange resin sodium polystyrene sulfonate on water uptake behavior of ranitidinehydrochloride. Drug resin complexes (DRC) were prepared and evaluated for thepercentage of moisture gain when placed in a humidity chamber at 40E2 °C and75E5% RH for 17 h as compared to drug and free resins under the same condition.Equilibrium moisture content (EMC) under different humidity conditions and therate and extent of moisture uptake in the presence (15 watt florescence light) andabsence of light under 40E2 °C and 75E5% RH were also calculated for DRCs,drug and unloaded resins. DRC 264 (containing polacrilex with H+) gained minimumweight (10.22%) maintaining free flowing characteristics whereas other resinatesshowed higher weight gain and formation of sticky mass while ranitidine HClturned liquid with gain of 28.11% weight. The rate of moisture uptake by ranitidineHCl 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. Eventhough DRC 264 contained ranitidine HCl, the moisture uptake rate was unaffectedby light and saturation in moisture gain was seen just at 6 h. Thus, loading ranitidineHCl on polacrilex resin with exchangeable H+significantly improves its moistureresistance and may not require very tight environmental controls during itsformulation.

Asimple, reproducible and rapid gas chromatographic method for precisedetermination of valproic acid (VPA) in human plasma has been developed. Totaltime for sample preparation and GC analysis is less than 45 min. After plasma proteinprecipitation, VPAwas extracted into chloroform with suitable recovery. By usingStabilwax®-DAcapillary GC column, a symmetrical gas chromatographic peak wasobtained without the need for derivatization. The calibration curve was proved tobe linear (r2 = 0.998) in a wide concentration range (0.45-100 μg/ml). Inter-day andintra-day accuracy and precision of this method was investigated during the methodvalidation and the method has good precision and accuracy. This method is highlyreproducible with a limit of detection 150 ng/ml of VPAin human plasma and couldbe used in TDM and pharmacokinetic studies.

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

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