The objective of the proposed method is to develop simple & accurate method for the determination of Rosiglitazonemaleate by UV spectrophotometric method in pharmaceutical dosage forms. Stock solution of Rosiglitazone was prepared & the calibration curve was drawn by suitable dilution of the standard solution. Commercially available Rosiglitazone tablet was taken & analysed. And the validation of the adopted method was ascertained by Precision & Accuracy. From the studies, it was found that, Rosiglitazone obeys linearity within the concentration range of 1-80µg/ml. From the results of precision study, it was found that the % R.S.D is less than 2%, which indicates that the method has good reproducibility. From the results of accuracy study, it was found that the % recovery values of pure drug from the pre-analysed solution of formulation were in between 97.5-98.12%, which indicates that the proposed method is accurate. The proposed method is specific while estimating the commercial formulations without interference of excipients and other additives.
Floating drug delivery systems have a bulk density lower than gastric fluids and thus remain buoyant in the stomach for a prolonged period of time, without affecting the gastric emptying rate. While the system is floating on the gastric contents, the drug is released slowly at a desired rate from the system. After the release of the drug, the residual system is emptied from the stomach. This results in an increase in the Gastric retention time. Addition of bio adhesive polymers will overcome the requirement for large quantity of fluid in the stomach for floatation. Rosiglitazonemaleate is an oral anti diabetic agent, which acts primarily by increasing insulin sensitivity. A gastro retentive dosage form will release the drug over an extended period in the stomach and upper gastro intestinal tract thus enhancing the opportunity for absorption.
Linearity of the peak area response was determined by making six measurements at six different concentrations point in the range of 160-260 µg/ml of sample Rosiglitazonemaleate respectively. The linear regression coefficient was calculated. The results are presented in Table.2 and Fig.2.
The aim of the present study was to prepare and evaluate matrix type transdermal patches of RosiglitazoneMaleate by using Ethylcellulose and Eudragit as polymers at different combinations to minimize adverse effects associated with oral administration. Transdermal patches of RosiglitazoneMaleate were prepared by solvent evaporation method by varying the blend ratios of Ethylcellulose and Eudragit. The drug polymer interaction studies were carried out by FT-IR studies. The prepared patches were evaluated for their thickness, weight variation, folding endurance, percentage moisture absorption, percentage moisture loss and drug content. In vitro drug release was determined by using Franz diffusion cell in phosphate buffer (pH5.4). The release data was studied for various kinetic parameters to understand the mechanism of drug release from the developed formulations. IR studies revealed that the drug, polymer and excipients were compatible with each other. Thin, flexible, smooth and uniform films were obtained with Eudragit and ethyle cellulose using dibutyl phthalate as plasticizer. Thickness, weights and drug contents of all the formulations remained almost uniform with low SD values. The formulations E6, E7 formulated by incorporating 1% span 80 and tween 80. E5 showed good release of drug than another formulations. Formulation E5 was prepared by combination of ethyl cellulose and Eudragit in the ratio of 1 :(1:5) the release rate of drug is 99.95 in 24hrs. Studies have shown promising results and there is a scope for further pharmacokinetic evaluation.
Three simple, accurate, economical and reproducible spectrophotometric methods for simultaneous estimation of two-component drug mixture of rosiglitazonemaleate and glimepiride in combined tablet dosage form have been developed. Developed methods are based on direct estimation of rosiglitazonemaleate at 318.0 nm, as at this wavelength glimepiride has zero absorbance and hence does not interfere. For estimation of glimepiride fi rst developed method involves formation and solving of simultaneous equation at 238.0 nm. Second developed method makes use two wavelength spectroscopy using 244.8 nm and 257.2 nm as two wavelengths. Third developed method is based on fi rst derivative spectroscopy using 252.0 nm as zero crossing point for estimation of glimepiride. All the developed methods obey Beer’s law in the concentration ranges employed for the respective methods. The results of analysis were validated statistically and by recovery studies.
Groups of young (3 mo) and aged (22 mo) male Wistar rats (Harlan, UK) were randomly assigned to control-treated and rosiglitazone-treated groups (n ⫽ 8 per group). All rats were housed in groups of three and maintained under vet- erinary supervision in a controlled environment (12 h light schedule; ambient temperature 22–23 °C) and all experi- ments were performed under a license issued by the De- partment of Health (Ireland) and in accordance with the guidelines laid down by the local ethical committee. Ani- mals had free access to food (standard laboratory chow; Red Mills, Ireland) and water and body weights were recorded throughout the study. Rosiglitazonemaleate (3 mg/rat) was administered daily in maple syrup (0.2 mL) for 56 d, while rats in the control groups received only maple syrup; each animal was given their daily oral dose individually by allowing them to suck the maple syrup containing the rosiglitazone from a 1 mL syringe. Previous experiments had established that treat- ment with rosiglitazone for this period attenuated the age- related decrease in LTP (Loane et al., 2009).
In this present study, floating mucoadhesive tablets of Rosiglitazone were formulated to improve the gastric retention time and overall bioavailability. Different mucoadhesive polymers like HPMC K200 M, Na CMC, Carbopol 974P, Karaya gum, Chitosan and Xanthan gum were selected to formulate the tablets. Various formulations were prepared by using these polymers in different concentration. The pre-compression blend of Rosiglitazone mucoadhesive tablets were characterized with respect to angle of repose, bulk density, tapped density, carr’s index and hausner’s ratio and all the results indicated that the blend was having good flow property and hence better compression properties. The swelling studies were performed for the formulations and the results depicted that all the formulations have a good swelling index. The drug release studies depicted that the formulations release the drug in first order. So based on the results, formulation RF13 was found to be an optimized formulation.
additional protons on N1 and N1A are trans to each other and interact through hydrogen bonds with the nonprotonated N2 and N2A nitrogen atoms [N1···N2= 2.800 (1) Å, N3···N4= 2.805 (1) Å]. The diprotonated macrocycle adopts an quadrangular (3,4,3,4)-C conformation (Fig. 1) according to Dale's nomenclature [(Dale, 1973 and 1976, (Hancock et al., 1996)], where the exo-cyclic nitrogen atom N2 is located two bonds away from the adjacent corner atoms C9A and C11, while the amine nitrogen atom N1A is located one bond away from the corresponding corner atom C9A and two bonds away from C11A. According to the stereochemical classification of 1,4,8,11 tetraazacyclotetradecane introduced by Bosnich et al. (1965), the cyclam ring adopts a trans-III geometry type, which, according to molecular mechanics MM- calculations, is the most stable among the five possible configurations (Bandoli et al., 1993). In the crystal structure, intramolecular hydrogen bonds occur, linking carboxylate O atoms in each maleate ion. The H3C and H7A atoms are involved in these bonds and maintain the charge balance by bridging two carboxylate groups within the structure. The complex features intra and intermolecular hydrogen bonds involving N—H···O, N—H···N and O—H···O. The main types of such bonds are those between protonated NH groups of the marcocycle and O atoms of the ionized maleic hydroxyls, between protonated and nonprotonated NH groups of the macrocycle and between O-atoms of the same ionized maleic hydroxyls as shown on Fig. 2 and 3. The values of the main H-bonds are reported in table 3.
The objective of the present investigation was to prepare orodispersible tablets of pheniramine maleate by direct compression method using three super disintegrants, viz., croscarmellose sodium, crospovidone and sodium starch glycolate at different concentrations with microcrystalline cellulose were used along with sodium bicarbonate and citric acid as effervescent agent. Orodispersible tablet is the fast growing and highly accepted drug delivery system, convenience of self administration, compactness and easy manufacturing. Pheniramine maleate is a member of alkylamine class of H 1 receptor antagonists. It is an antihistamine used in
The majority of infantile hemangiomas (IHs) proliferate, stabilize, and regress without the need for intervention beyond anticipatory guidance. However, in a significant minority, size or location may necessitate intervention to treat or prevent local disfigurement, functional impairment, or systemic complications. Oral propranolol is now approved by the US Food and Drug Administration for treating IHs that require intervention. Topical β -blockers, most commonly timolol maleate, are also reportedly effective for the treatment of less aggressive IHs, but many questions remain about their effectiveness and possible adverse effects.
The drug content was found in the range of 99.3 % - 101.1% (acceptable limit). Friability of the tablets was found below 0.34% and hardness was found between 4.0-5.2kg/cm 2 , indicating a good mechanical resistance of the tablets, and the parameters were found well within the specified limit. (Table No.5). The standard curve of domperidone maleate is excellent linearity and R 2 =0.999 in phosphate buffer & R 2 =0.998 0.1 N HCl (Fig. 1,2). The in- vitro disintegration time (DT) of the tablets was found to less than 1 min. Tablets containing 3.5% Sodium starch glycolate and 3.5% Croscarmellose sodium had disintegration
The structure consists of a protonated 2,5-dimethylanilinium cation with the hydrogen maleate anion (Fig. 1). H1 of the maleate anion undergoes intramolecular O—H···O hydrogen-bonding with O3 as the acceptor. This is common in many structures of maleic acid as the cis disposition of the alkene places hydrogen bonding donors and acceptors in close proximity. As such, the maleate anion is very flat (mean deviation from a least-squares plane composed of atoms O1–O4, C9–C12, H1 of 0.04 Å). Parallel maleate anions pack in layers in between layers of parallel 2,5-dimethylanilinium cation layers. The cation layers are parallel with the ab plane at c = 0. The anion layers are parallel with the ab plane at c = 1/2 (Fig. 2). The hydrogen atoms of the protonated amine (H1A, H1B, H1C) undergo intermolecular N—H···O hydrogen- bonding interactions with oxygen atoms of three different maleate anions. The two hydrogen-bonding motifs dominating the structure are R 4
Niosome entrapped chlorpheniramine maleate was estimated by ultracentrifugation method. The entrapment efficiency of niosomes was determined by ultra centrifuging the niosomal dispersions at 4,000 rpm for 30min.the clear supernatant was analyzed for chlorpheniramine maleate spectrophotometrically at ƛmax 261 nm and gave the amount of unentrapped drug. Amount of entrapped drug was obtained by subtracting amount of unentrapped drug from the total drug incorporated.
The red line, however, calculated by simple collapsing all 2 × 2-tables without stratification by trial, decreases. The reason is that there are many unbalanced trials with the treatment groups being larger than the control groups and simultaneously having the lowest event rates (see Figure 2, left panel). We can visualize this by adding further ele- ments to this plot. The starting and ending points of the single trial lines are marked by diamonds with size pro- portional to the size of the control group and the treat- ment group of this trial, respectively. If this is done, the contribution of single trial arms to the red line becomes visible. In our example, we have a large trial with many events in the control group (left) and, on the other hand, many trials with a larger proportion of rosiglitazone patients having low event rates (right-hand side).
Flupirtine is a non-opioid analgesic without antipyretic or antiphlogistic properties. Flupirtine is a centrally acting analgesic but the analgesic action of flupirtine does not depend on any central opioid effect. The fact behind this statement is that the pain-relieving property of flupirtine is not reduced by the opioid antagonistic drug naloxone. Flupirtine has been reported for its neuro-protective properties and possess a selective neuronal potassium channel opener that also has NMDA receptor antagonist properties. Flupertine is transformed into two primary derivatives, 4-fluoro-hippuric acid and the Nacetylated analogue D13223. Both derivatives of are flupirtine pharmacologically active with 30% of the analgesic potency of the parent drug and further oxidized and then conjugated with glycine to form inactive metabolites, Recently, Flupirtine maleate has been introduced in Indian market in oral, intravenous and rectal dosage forms. The half life of flupirtine following intravenous administration was 1.8 hours, while the plasma elimination half life in healthy young volunteers following single dose administration of flupirtine by the intravenous, oral and rectal routes was 8.5, 9.6 and 10.7 hours respectively. There is plenty of literature available on the effect of Flupirtine maleate on chronic and acute pain management. These preliminary finding require confirmation in further comparative studies. Keywords: Flupirtine maleate, Naloxone, Opioid, NMDA
Three Simple, accurate and reproducible UV spectrophotometric methods were established for the assay of pyrilamine maleate (PYRA) based on the formation of ion-association products between PYRA and cobaltous thiocyanate (CTC), citric acid (CA) and Alizarin red S (ARS). The optical characteristics such as Beers law limits, molar absorptivity and Sandell’s sensitivity for the methods (M 1 -M 3 ) are given. The absorbance was measured at 620 (CTC-M 1 ), 580 (CA-M 2 )
Rosiglitazone, a specific PPAR-γ agonist, has been used in diabetic therapy. Previously, a substantial number of studies showed that by means of PPAR-γ activation, rosiglitazone exerted multiple cardio-protective effects [18-21]. For example, Gonon AT et al. reported that via increasing NO production, rosiglitazone preserved cardiac function in mice with ischemic insult . In another study reported by Molavi B et al. that in rats with ischemia-reperfusion injury, rosiglitazone exerted robust cardio-protective effects as compared to the control group. Furthermore, via PPAR-γ activation, rosiglitazone could also decrease the infarct size related to the area at risk in the swine heart with ischemia-reperfusion injury . Basically, all the benefits of PPAR-γ confer to cardio- vascular system may largely due to its effects on increasing NO production and ameliorating inflammation and oxida- tion. However, whether rosiglitazone was beneficial for endothelium protection in dyslipidemia has less known, and whether rosiglitazone added on atorvastatin had syn- ergistic effects on endothelium protection had not been investigated yet.
An increase in mitochondrial content, respiration, and fatty acid oxidation in WAT would be expected to cause a decrease in adi- posity. Paradoxically, animals treated with rosiglitazone displayed a very small but significant increase in body weight, consistent with the known effect of PPARγ activation to induce adipogenesis. The increase in body weight was not accompanied by a detectable increase in the weight of the epididymal fat pads, suggesting that it may be due to fat accumulation in other depots. Interestingly, a “redistribution” of fat from visceral to peripheral depots has been observed to occur in response to treatment with thiazolidin- ediones in rodents and humans (19–23). These results suggest the hypothesis that rosiglitazone produces two simultaneous effects: one to increase adipogenesis and second to increase fat utilization by increasing mitochondrial mass, fatty acid oxidation, and oxy- gen consumption. These two effects may be differentially elicited in a depot-specific manner, leading to an overall increase in body weight while decreasing visceral adiposity. Further work will be required to directly test this hypothesis. Interestingly, pioglitazone has been reported to enhance daily profiles of energy expenditure and lipid utilization in diabetic rats with no changes in body weight (24), suggesting differences between animal models in the predominant responses to thiazolidinediones.
flasks were kept aside for 10 min with occasionally shaking before diluting to the mark with water. The absorbance was recorded after 5 min at 340 nm against a reagent blank, using PC Shimadzu UV Spectrophotometer. The standard curve of Enalapril Maleate was plotted between different concentration Vs absorbance. Results are given in Table 6 and Fig. 1. Drug Polymer Compatibility study by FTIR Spectroscopy 18 : FTIR Study is one of the important analytical techniques to predict the presence of certain functional groups which are observed at a definite frequency. A peak-by-peak correlation is excellent evidence for identity. The drug-polymer interaction was studied by FTIR spectroscopy given in fig. 6 & 7 and Table 15.
In terms of drug disposition, rosiglitazone is prin- cipally metabolised in the liver by the cytochrome P450 (CYP) 2C8 enzyme, and to a lesser extent by CYP2C9. 3,14 The most frequently studied variant allele in the CYP2C8 gene is CYP2C8*3, which comprises two linked polymorphisms at codon 139 and codon 399 (Arg139Lys; Lys399Arg). In vitro , the CYP2C8*3 allele has been associated with decreased metabolic activity of the CYP2C8 enzyme. 15 – 17 In vivo, however, the effects of CYP2C8*3 appear to be substrate dependent, with reports of both increased and decreased metabolism of different CYP2C8 sub- strates. One clinical study showed that the CYP2C8*3 allele is associated with decreased rosigli- tazone plasma drug exposure in healthy volunteers; however, two other studies have shown no significant associations between the CYP2C8*3 allele and rosi- glitazone pharmacokinetics in humans. 18 – 20