Formulation and in vitro evaluation of directly compressed controlled release tablets designed from the Co-precipitates

Controlled release dosage forms provide sustained therapeutics effects for prolonged period of time and improve patient compliance. In present study, controlled release co-precipitates of Metoprolol Tartrate and Losartan Potassium were prepared by solvent evaporation method using polymers such as Eudragit RL 100 and Carbopol 974PNF and controlled release tablets were directly compressed into tablets. In-vitro dissolution of controlled release coprecipitates were performed by USP Method-II [paddle method] and tablets were evaluated by USP Method-I [rotating basket method] in phosphate buffer [PH 6.8] using pharma test dissolution apparatus. The temperature was maintained constant at 37 +/- 1.0 0 C and the rotation speed of paddle and basket was kept constant at 100rpm. Drug release mechanisms were determined by applying Power Law kinetic model. The difference and similarity of dissolution profiles test formulations with reference standards were also determined by applying difference factor [f1] and similarity factor [f2]. The results showed that the controlled release co-precipitates with polymer Eudragit RL 100 of both the drug extended the drug release rates for 10 hours and those having polymer Carbopol 974P NF extended the drug release rates for 12 hours. The controlled release tablets prepared from controlled release co-precipitates extended the drugs release up to 24 hours with both the polymers. The drug was released by all tests anomalous non fickian mechanism except F1 and F5 do not follow Power Law. The f1 and f2 values obtained were not in acceptable limits except F15 whose values were in acceptable limits. It is concluded from the present study that polymers [Eudragit RL 100 and Carbopol 974P NF] can be efficiently used in development of controlled release dosage forms having predictable kinetics

Study of the effect of inorganic and organic complexes of arsenic metal on the status of GSH in T. cells and B. cells of blood

Arsenic is a major threat to large part of the population due to its carcinogenic nature. The toxicity of Arsenic varies with its chemical form and oxidation states. Glutathione [GSH], a major intra-cellular tripeptide plays a major role in arsenic detoxification. The present study was designed to provide insight into the extent of changes in GSH level by inorganic arsenic in the form of Arsenic trioxide [ATO] and organic arsenic in the form of nitro benzene arsenic acid [NBA]. Lymphocytes [T.cells and B.cells] were investigated for determination of change in GSH metabolic status caused by arsenic. The depletion of GSH level positively correlated with increasing arsenic concentration and time of incubation. The decline in GSH level was consistent with increasing pH and physiological temperature. Our findings show that changes in GSH status produced by Arsenic could be due to adduct [As-[SG][3]] formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of inorganic and organic arsenicals. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity

Development of a novel ketoprofen transdermal patch: effect of almond oil as penetration enhancers on in-vitro and ex-vivo penetration of ketoprofen through rabbit skin

The aim of the study was to formulate and evaluate topically applied ketoprofen gels and patches and to see the effect of naturally occurring almond oil as penetration enhancer on the penetration of ketoprofen through artificial membrane/rabbit skin. Prior to ketoprofen gel and patch formulation, the particle size and particle size determination of ketoprofen was analyzed by Particle size analyzer [Horiba LA300]. Ketoprofen gels and patches were formulated and almond oil was added in several concentrations i.e. 0.5%, 1%, 1.5%, 2%, 2.5% and 3%. The formulated gels were evaluated by several parameters like pH, spreadibility, consistency, homogeneity, skin irritation and drug content determination. In vitro drug permeation studies from transdermal gels and patches were carried out across artificial membrane and rabbit skin by using Franz Cell Apparatus [PermeGear, USA]. Kinetics model was employed to the release patterns of ketoprofen from gel and patches in order to investigate the drug transport mechanism. The cumulative amount of drug penetrated from different formulations was statistically evaluated by using One-way analysis of variance [ANOVA]. Stability study was performed for various batches of ketoprofen transdermal gel. Almond oil as penetration enhancer in various concentrations significantly enhances the penetration of drug from transdermal gels and patch across synthetic membrane/rabbit skin but was most significant when used in 3% concentration

Study of the effects of BaCl[2] on the level of glutathione in plasma and cytosolic fraction in whole blood

Barium has important role in the field of medical sciences, but it has been found in various studies that barium can cause numerous toxic effects. Studies have proven the strong affinity of the metalloelements for the sulfhydryl group [SH], present in reduced glutathione [GSH] and other biological molecules. In this context, the study about the possible interaction of BaCl[2] with glutathione in whole blood components was of interest, as an indication about the extent of barium toxicity and the role of glutathione in the conjugation and detoxification of the metalloelement barium. The concentration dependent and time dependent effect of BaCl[2] on the level of GSH in plasma and Cytosolic Fraction in whole blood was investigated, following Ellman's method. It was found that BaCl[2] causes a decrease in the GSH level, which is more pronounced with increasing concentration of BaCl[2] and with time incubation as well. The observed effect GSH concentration may be presumably due to production of oxidized glutathione [GSSG] or then due to Barium-Glutathione [GS-Ba-SG] conjugate formation

Evaluation of the interaction of vanadium with glutathione in human blood components

Metallo-elements including Vanadium [V] have strong affinity for sulfhydryl [-SH] groups in biological molecules including Glutathione [GSH] in tissues. Because of this fact it was of interest to further investigate the interaction of Ammonium Vanadate [NH[4]VO[3]] with Glutathione as a biomarker of toxicity and the role of Glutathione in the detoxification and conjugation processes in whole blood components including plasma and cytosolic fraction. Effects of different concentrations of Ammonium Vanadate [NH[4]VO[3]] on the level of reduced Glutathione in whole blood components [Plasma and Cytosolic fraction] were examined. GSH depletion in plasma and cytosolic fraction was Ammonium Vanadate's concentration-dependent. Depleted GSH level was more pronounced with more incubation time period. These findings show that changes in the GSH status produced by Ammonium Vanadate could be due to either by adduct formation of Vanadium and glutathione i.e. [V-SG] or by increased production of oxidized Glutathione [2GSH +V[+5] - GSSG]. This change in GSH metabolic status provides some information regarding the mechanism of toxicity by Ammonium Vanadate and the protective role of glutathione

Formulation and in vitro evaluation of ofloxacin-ethocel controlled release matrix tablets prepared by wet granulation method: influence of co-excipients on drug release rates

Being controlled release dosage forms, tablets allow an improved absorption and release profiles of Ofloxacin. The fact that drugs with fine particles size can be compressed well after wetting, so in our research studies Ofloxacin controlled release matrix tablets were prepared by wet granulation technique. In order to investigate the potential of Ethyl cellulose ether derivatives as a matrix material, Ofloxacin formulations with different types and grades of Ethocel were prepared at several drug-to-polymer ratios. The method adopted for in vitro drug release studies was USP Method-1 [rotating Basket Method] by Pharma test dissolution apparatus using phosphate buffer 7.4 pH as a dissolution medium. Various Kinetic models were employed to the formulations for the purpose of determination of release mechanism. A comparative study was performed between the tested Ofloxacin-Ethocel formulations and a standard reference obtained from the local market. FI dissimilarity factor and f2 similarity factor were applied to the formulations for the checking of dissimilarities and similarities between the tested formulations and reference standard

Effect of lithium metal on the chemical status of glutathione [GSH] present in whole blood [especially in plasma and cytosolic fraction in human blood]

Lithium remains a mainstay in the acute and prophylactic treatment of bipolar affective disorder. It is used in the augmentation of antidepressant treatment and, less frequently, in the augmentation of antipsychotic treatment of schizophrenia. It is reported to have specific anti-suicidal effects. Thus the effect of Lithium was interesting to study on the glutathione [GSH] level in vivo conditions. Ellman's method has been used to see the effect of lithium on glutathione [GSH] level in whole blood. The time dependent effect of Lithium on the chemical status of glutathione [GSH] was determined in the whole blood [Plasma and cytosolic fraction] of human. The concentration of Glutathione was drastically decreased. The decrease in the glutathione level was concentration and time of interaction dependent, probably due to oxidation of glutathione [GSH] to corresponding disulphide [GSSG]. In this paper the effect of Lithium on the Thiol/GSH level was discussed in vitro, which in principal may present a model of in vivo reaction