Sodium Dihydrate Research Articles

Estimation of loxoprofen sodium dihydrate in tablets by reverse phase high performance liquid chromatography

A simple and rapid reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for the estimation of loxoprofen sodium dihydrate (LSD) in tablets. An isocratic HPLC analysis was performed on Phenomenex, Luna C18(2) (250×4.6mm, 5μ) column. The compound was separated with the mixture of 0.4% orthophosphoric acid and acetonitrile in the ratio of 45:55 (v/v) as a mobile phase at a flow rate of 1.0mL/min. UV detection was performed at 210nm. Run time per sample was 8min with the retention time of 4.9min. The system suitability parameters, such as theoretical plate count, tailing and% RSD between six standard injections were within the limits. The method was validated according to ICH guidelines. The method was validated for specificity, precision, linearity, stability of sample solution, intermediate precision, robustness and accuracy. The stability of the sample solution was checked for 24h at one hour intervals. The results show that the sample solution is stable for at least 24h. Calibration plots were linear over the concentration range of 10–90μg/mL as indicated by the correlation coefficient of 0.9992. The% RSD was 0.115 and 1.288 for system precision and method precision, respectively. The % RSD values for intermediate precision studies were less than 2%. The robustness of the method was evaluated by deliberately altering the chromatographic conditions and the results were adhered with the limits. The high recovery and low relative standard deviation confirm the suitability of the method for the estimation of loxoprofen sodium dihydrate in tablets.

Determination of the scale of segregation of low dose tablets using hyperspectral imaging

In this work, near infrared (NIR) hyperspectral imaging was used to quantify the spatial distribution of drug in tablets containing tolmetin sodium dihydrate. Hyperspectral data cubes were generated by imaging the same spatial region of a sample while illuminated by a laser at a different wavelength for each image. Images were generated for wavelengths ranging from 1100 to 2200 nm. Ten tablets with concentrations ranging from 0.0 to 10.0% w/w tolmetin were imaged, and the scales of segregation were calculated for the tablets. Lactose anhydrous was used as the diluent, and all mixtures contained 0.5% magnesium stearate as a lubricant. This research has shown hyperspectral imaging to be viable tool for quantifying segregation of low dose drugs in tablets.

Preparation and solid state characterisation of chlorothiazide sodium intermolecular self-assembly suprastructure

Chlorothiazide (CTZ), unlike other thiazide diuretics, can form salts. An injectable formulation containing the sodium salt is available; however neither the physicochemical characteristics of the salt nor its solid state form have been previously reported. This work reports on the crystal structure of chlorothiazide sodium. The structure was investigated by single crystal X-ray and nuclear magnetic spectroscopy (NMR) analyses and compared to chlorothiazide, while the solid state characteristics were assessed by thermal analysis, powder X-ray diffraction, infrared spectroscopy, dynamic moisture sorption and solubility analysis. The crystal structure of chlorothiazide sodium was determined to be triclinic; the crystal space group type was P-1. Chlorothiazide sodium presented a self-assembly polymeric-type suprastucture, where the unit cell comprised two chlorothiazide molecules bonded together with sodium cations through the water bridges. The coordinate centre comprised the following: (CTZ) 3·(H 2O)·Na(H 2O) 2Na·(H 2O)·(CTZ) 3. The crystalline material was determined to be a monosodium dihydrate, stable in the range of 10–90% relative humidity (RH) at 25 °C. Additional processing of the salt resulted in a crystalline anhydrous form which was stable in the range 0–20% RH at 25 °C. The aqueous solubility of the chlorothiazide sodium dihydrate at 37 °C was found to be approximately 400-fold higher than that of chlorothiazide, which may present biopharmaceutical advantages for the salt compared to the non-salt form.

Bioavailability of ibuprofen following oral administration of standard ibuprofen, sodium ibuprofen or ibuprofen acid incorporating poloxamer in healthy volunteers

BackgroundThe aim of this study was to compare the pharmacokinetic properties of sodium ibuprofen and ibuprofen acid incorporating poloxamer with standard ibuprofen acid tablets.MethodsTwenty-two healthy volunteers were enrolled into this randomised, single-dose, 3-way crossover, open-label, single-centre, pharmacokinetic study. After 14 hours' fasting, participants received a single dose of 2 × 200 mg ibuprofen acid tablets (standard ibuprofen), 2 × 256 mg ibuprofen sodium dihydrate tablets (sodium ibuprofen; each equivalent to 200 mg ibuprofen acid) and 2 × 200 mg ibuprofen acid incorporating 60 mg poloxamer 407 (ibuprofen/poloxamer). A washout period of 2-7 days separated consecutive dosing days. On each of the 3 treatment days, blood samples were collected post dose for pharmacokinetic analyses and any adverse events recorded. Plasma concentration of ibuprofen was assessed using a liquid chromatographic-mass spectrometry procedure in negative ion mode. A standard statistical ANOVA model, appropriate for bioequivalence studies, was used and ratios of 90% confidence intervals (CIs) were calculated.ResultsTmax for sodium ibuprofen was less than half that of standard ibuprofen (median 35 min vs 90 min, respectively; P = 0.0002) and Cmax was significantly higher (41.47 μg/mL vs 31.88 μg/mL; ratio test/reference = 130.06%, 90% CI 118.86-142.32%). Ibuprofen/poloxamer was bioequivalent to the standard ibuprofen formulation, despite its Tmax being on average 20 minutes shorter than standard ibuprofen (median 75 mins vs 90 mins, respectively; P = 0.1913), as the ratio of test/reference = 110.48% (CI 100.96-120.89%), which fell within the 80-125% limit of the CPMP and FDA guidelines for bioequivalence. The overall extent of absorption was similar for the three formulations, which were all well tolerated.ConclusionIn terms of Tmax, ibuprofen formulated as a sodium salt was absorbed twice as quickly as from standard ibuprofen acid. The addition of poloxamer to ibuprofen acid did not significantly affect absorption.

Onset of analgesia with sodium ibuprofen, ibuprofen acid incorporating poloxamer and acetaminophen—a single-dose, double-blind, placebo-controlled study in patients with post-operative dental pain

To compare the onset of action and efficacy of sodium ibuprofen (ibuprofen sodium dihydrate) and ibuprofen acid incorporating poloxamer (ibuprofen/poloxamer) with that of acetaminophen and placebo in patients with post-operative dental pain. A double-blind, randomised, placebo-controlled, active comparator, two-centre study assessing the analgesic efficacy of sodium ibuprofen (512 mg, equivalent to 400 mg ibuprofen acid), ibuprofen/poloxamer (containing 400 mg ibuprofen acid and 120 mg poloxamer 407), acetaminophen (1000 mg) and placebo in patients with moderate-to-severe pain after third molar extraction (n = 322). Onset of action was assessed using the two-stopwatch technique, and pain intensity and relief were measured using validated traditional descriptor scales. Significantly more patients achieved confirmed perceptible pain relief and meaningful pain relief with sodium ibuprofen (96.3%, P < 0.0001) and ibuprofen/poloxamer (90.0%, P = 0.0005) than with acetaminophen (67.5%). The onset of action of both ibuprofen formulations was comparable with that of acetaminophen up to 45 min post-dose; a marked divergence in onset times in favour of the ibuprofen formulations occurred from 45 min onward. Mean values for the area under the pain relief and pain intensity differences curve (0-6 h) were significantly greater for sodium ibuprofen (3.46) and ibuprofen acid (3.49) than for acetaminophen (2.25) (P < 0.001). Other pain relief and pain intensity endpoints favoured both ibuprofen formulations over acetaminophen. Distractibility from pain (6 h) was significantly greater with the ibuprofen formulations than with acetaminophen (P = 0.008 for sodium ibuprofen; P = 0.03 for ibuprofen/poloxamer). In patients receiving ibuprofen, pain interfered less with daily activities (at 1 and 6 h) than in those receiving acetaminophen (P <or= 0.015). Both ibuprofen formulations had significantly better mean global assessment scores than acetaminophen (P < 0.001). Tolerability profiles of the ibuprofen formulations were comparable with that of acetaminophen. Compared with acetaminophen, sodium ibuprofen was associated with significantly greater analgesic efficacy, pain relief in a greater proportion of patients and greater patient satisfaction.

Ibuprofen sodium dihydrate, an ibuprofen formulation with improved absorption characteristics, provides faster and greater pain relief than ibuprofen acid

The objective of this 6-hour study was to compare rate of pain relief, analgesic efficacy and tolerability of a novel ibuprofen formulation, ibuprofen sodium dihydrate, with that of ibuprofen acid in subjects with postoperative dental pain. The test formulation of ibuprofen sodium dihydrate (256 mg sodium salt) and the reference product both contain 200 mg ibuprofen. Subjects with moderate-to-severe pain after extraction of third molars were randomized to receive two tablets of either ibuprofen sodium dihydrate (198 subjects) or ibuprofen (198 subjects) in this double-blind, multicenter trial. Pain was measured using traditional descriptor scales and onset of analgesia assessed using the stop-watch method. Median time to substantial pain relief occurred 14 minutes earlier in the ibuprofen sodium dihydrate group (p < 0.001). The first sign of pain relief, an increase in relief and time until the pain was half gone occurred significantly earlier and faster in the ibuprofen sodium dihydrate-treated patients (p < 0.02-0.00003). Corresponding numbers needed to treat were in the range 11. Reduction in pain intensity was evident within 5 minutes (p < 0.01) in the ibuprofen sodium dihydrate group compared to 15 minutes in the ibuprofen group. Pain intensity was reduced to half after 30 and 57 minutes in the ibuprofen sodium dihydrate and ibuprofen groups, respectively (p < 0.025). The overall analgesic efficacy in terms of summed pain intensity differences (SPID), total pain relief (TOTPAR) and remedication times in the two groups were similar. Both treatments were well tolerated and no serious events occurred. Ibuprofen sodium dihydrate provides faster and more efficacious pain relief during the first hour after intake when compared to a conventional ibuprofen acid formulation. The tolerability profiles are similar.

Structures of racemic lithium tartrate hydrates

Racemic dimetal tartrate hydrates were obtained from the reaction of d, l-tartaric acid with LiOH and MOH, where M = Li, Na, K, Rb, Cs, NH 4. Dilithium trihydrate Li 2(C 4H 4O 6) · 3H 2O ( 1) consists of two distinct two-dimensional coordination networks [Li 6(C 4H 4O 6) 3(H 2O) 9] n (A) and [Li 2(C 4H 4O 6)(H 2O) 3] 2 n (B) which are arranged parallel in BAABAA fashion. Lithium sodium dihydrate LiNa(C 4H 4O 6) · 2H 2O ( 2) is as a three-dimensional coordination network in which discrete centrosymmetric [Li(C 4H 4O 6)(H 2O)] 2 units are linked by NaO 6 polyhedra. The monohydrates LiM(C 4H 4O 6) · H 2O with M = K ( 3), Rb ( 4), Cs ( 5) are three-dimensional coordination networks which are isostructural with the hydrogen-bonded ammonium analogue, M = NH 4 ( 6). These structures are composed of [LiM(C 4H 4O 6)(H 2O)] n layers linked by MO 8 and MO 10 polyhedra. Different patterns of hydrogen bonding between tartrate ions and water molecules are observed in structures 1, 2 and the series of 3– 6.

Pharmacokinetics of ibuprofen sodium dihydrate and gastrointestinal tolerability of short-term treatment with a novel, rapidly absorbed formulation

This paper describes four studies investigating the dissolution, plasma pharmacokinetics and safety of a novel, fast-acting ibuprofen formulation, ibuprofen sodium dihydrate. Four separate studies investigated: the in vitro dissolution rates of ibuprofen sodium dihydrate (at pH 1.2, 3.5 and 7.2); the bioavailability of ibuprofen sodium dihydrate (in two pharmacokinetic studies; combined n = 38) compared with conventional ibuprofen, ibuprofen lysinate, ibuprofen arginate and ibuprofen liquagels (all 2 x 200 mg ibuprofen); and the gastroduodenal tolerance of ibuprofen sodium dihydrate and ibuprofen arginate (both 2 x 200 mg ibuprofen t.i.d.) in an endoscopy safety study, where endoscopy was performed at baseline and at the end of each treatment period using a five-point scale to assess the integrity of the gastric and duodenal mucosa. Ibuprofen sodium dihydrate dissolved significantly more rapidly at pH 1.2, 3.5 and 7.2 than conventional ibuprofen, ibuprofen lysinate and ibuprofen liquagels. Ibuprofen sodium dihydrate had similar C(max) to ibuprofen lysinate and ibuprofen liquagels and significantly higher Cmax than conventional ibuprofen (p = 0.002). The mean plasma concentration for ibuprofen sodium dihydrate was significantly higher than for conventional ibuprofen (p = 0.028) 10 minutes post-dose and the t(max) for ibuprofen sodium dihydrate was reached significantly earlier than for conventional ibuprofen (p = 0.018). All three formulations were bioequivalent according to the acceptable boundaries (90% confidence intervals). No statistically significant difference was observed between the ibuprofen formulations in terms of adverse events and specifically with respect to hemorrhagic scores; 41 (46.0%) adverse events (AEs) occurred after administration of ibuprofen sodium dihydrate, and 46 (52.9%) after ibuprofen arginate. One occurrence of an invasive ulcer was observed after administration of ibuprofen arginate. The new formulation of ibuprofen sodium dihydrate dissolves quickly in vitro, has the same extent of absorption as other fast-acting ibuprofen formulations, and is absorbed into plasma more rapidly than conventional ibuprofen. In addition, the present studies suggest that the tolerability and safety profile of ibuprofen sodium dihydrate is comparable to existing ibuprofen formulations.

Reply to the discussion by William G. Hime of “The use of tension testing to investigate the effect of w/c ratio and cement type on the resistance of concrete to sulfate attack”

This brief discussion contains the original authors' replies to a commentary on their study (Boyd and Mindess, 2004) on concrete specimens that were cast and partially immersed in a solution for varying periods of time up to 1 year. The study found that water/cement (w/c) ratio had a greater influence on the resistance of the concretes to than did cement type. In addition, the pressure tension test appeared to be more sensitive than the compressive strength test in detecting internal damage, particularly at early ages. In the commentary, Hime contended that the term sulfate attack is not adequately defined, nor is the distress under investigation necessarily confined to at all; it may be due to physical salt due to precipitation of sodium as either thenardite or mirabilite or both. Hime also noted that the authors fail to provide any explanation why the tests fail to show any loss from the initial measurement of the prisms in sodium solution, except for one type of cement studied. Boyd and Mindess reply to these concerns by claiming that Hime has misunderstood the intent of the original paper, which was to examine the use of a novel tension testing technique to determine the extent of internal damage to concrete. The paper was not intended to deal with the mechanisms of attack. Boyd and Mindess do note, however, that in common engineering usage, sulfate attack is the term used for chemical processes involving ions reacting with the components of the cement paste, such as the formation of ettringite, gypsum, thaumasite, and sodium dihydrate. The authors conclude by turning down Himes' offer to carry out a further microscopic investigation of the research specimens; said specimens have been discarded.

HPLC and chemometric methods for the simultaneous determination of cyproheptadine hydrochloride, multivitamins, and sorbic acid

Three methods are presented for the simultaneous determination of cyproheptadine hydrochloride (CP), thiamine hydrochloride (B1), riboflavin-5-phosphate sodium dihydrate (B2), nicotinamide (B3), pyridoxine hydrochloride (B6), and sorbic acid (SO). The chromatographic method depends on a high performance liquid chromatographic (HPLC) separation on a reversed-phase, RP 18 column. Elution was carried out with 0.1% methanolic hexane sulphonic acid sodium salt (solvent A) and 0.01M phosphate buffer containing 0.1% hexane sulphonic acid sodium salt, adjusted to an apparent pH of 2.7 (solvent B). Gradient HPLC was used with the solvent ratio changed from 20:80 to 70:30 (over 9min), then to 80:20 (over 11min) for solvent A:B, respectively. Quantitation was achieved with UV detection at 220 and 288nm based on peak area. The other two chemometric methods applied were principal component regression (PCR) and partial least squares (PLS). These approaches were successfully applied to quantify each drug in the mixture using the information included in the UV absorption spectra of appropriate solutions in the range 250–290nm with the intervals Δλ=0.4nm at 100 wavelengths. The chemometric methods do not require any separation step. The three methods were successfully applied to a pharmaceutical formulation and the results were compared with each other.

Nondestructive measurements of the compact strength and the particle-size distribution after milling of roller compacted powders by near-infrared spectroscopy

Compact strength and the particle-size distribution of milled roller compacted compacts were correlated to the slope of the best-fit line through near-infrared spectra for samples prepared under different roll speeds and feed rates. The above correlations were found to hold for compacts prepared from microcrystalline cellulose powder as well as from a typical direct compression pharmaceutical powder blend containing tolmetin sodium dihydrate, microcrystalline cellulose, and dicalcium phosphate dihydrate. Near-infrared spectra were also collected real time for the compacts prepared from the tolmetin powder blend. The real-time slope values for the spectra showed good agreement with the off-line data. The strength of compacts was determined using three-point beam bending method and the particle-size distribution of the milled compacts was determined using sieve analysis. The results suggest that the real-time values of the slope of the best-fit line through the near-infrared spectrum offers a robust, yet simple and fast quality control tool to monitor/control manufacturing and scale-up processes involving dry granulation by roller compaction.

Thermal analysis, Raman scattering and infrared spectroscopy versus temperature of hydrogen bonds in sodium p‐nitrophenolate dihydrate (NPNa), [Na(C6H4ONO2)] · 2H2O

AbstractThis work deals with the hydrogen bonds in p‐nitrophenolate sodium dihydrate (NPNa). Differential scanning calorimetry (DSC) and thermogravimetric analysis (TG) were performed in the temperature range 293–673 K (20–400 °C) in order to control the dehydration process and decomposition of the crystal. The energy necessary to break each type of hydrogen bond has been determined. The O…O vibration of the two hydrogen bonds, denoted O…O1 and O…O2, have been studied by Raman spectroscopy versus temperature. The O–H stretching modes of hydrogen bonds have been also identified in infrared and micro‐Raman spectra. Raman spectra functions of temperature allowed to evidence an order‐disorder transition at ca 138 K related to the molecular configuration in the lattice.

Effect of tolmetin sodium dihydrate on adhesion formation by intraperitoneal administration of antineoplastic agents.

Antineoplastic agents are currently being administered through catheters placed intraperitoneally to treat cancer localized to the peritoneum. This route allows for high local concentrations of antineoplastic drug at the tumor site with low levels of the drug systemically, thereby reducing the systemic toxicity. However, there are complications with this mode of delivery, including a decrease in catheter patency and induction of adhesion formation, which leads to decreased drug dispersion and limits continuing drug administration. A model was developed in rats to mimic this method of antineoplastic drug administration that produced fibrin deposition around the catheter and adhesion formation involving bowel, intestines and liver. All antineoplastic agents tested, including Adriamycin, methotrexate, bleomycin, mitoxantrone and cisplatin, induced moderate to severe adhesion formation with varying effects on catheter patency. When an intraperitoneal bolus of tometin encapsulated in liposomes was tested with Adriamycin delivered via an osmotic minipump, a reduction in adhesion formation was observed. However, highly significant adhesion reduction was found when tolmetin was coadministered with the antitumor agents.

Differential pulse polarographic assay of tolmetin sodium capsules

Differential pulse polarography (DPP) is proposed as a direct method for the quantitation of tolmetin sodium in a capsule formulation (Tolectin--200 mg as the sodium dihydrate salt). Classical direct-current (DC) polarography has been employed to investigate the nature of the reduction occurring at the surface of the dropping mercury electrode (DME) using acetate buffer of pH 5.0 as the supporting electrolyte. The mean value of the results obtained by DPP expressed as a percentage of the stated amount, and the standard deviation, were found to be 99.87 +/- 0.43. The standard addition procedure used to assess the accuracy of the proposed method gave a mean percentage recovery of the total drug of 100.15 +/- 0.75%.

Hypocalcemic action of the several types of salicylic acid analogues.

The present study was performed to see the structure-activity relationships on the aspirin-induced hypocalcemia. Several kinds of salicylic acid (SA) analogues administered orally with a stomach tube. In general, the drugs were suspended in the 2% CMC solution. At the scheduled times after the treatment, 60 microliters of the blood was collected to determine the level of calcium. Aspirin, sodium salt of o-hydroxybenzoic acid (Na-salicylate), sodium salt of m- and p-hydroxybenzoic acid (HBA), 2,5-dihydroxybenzoic acid (DHBA), PAS sodium dihydrate (PAS-Na), salicylamide (SAM) and 2% CMC control were used. Hypocalcemia was induced by aspirin and Na-salicylate but not by m- and p-HBA-Na. In addition, DHBA and PAS caused hypocalcemia when they were administered intravenously but not orally. These results suggest that the carboxyl group must be adjacent to the hydroxyl group on the benzene ring to induce this type of hypocalcemia and that the SA structure would be able to induce hypocalcemia, even in the presence of the additional third substituent on the same ring. On the comparison between aspirin-DL lysine (water soluble aspirin) and SA-DL lysine, SA-DL lysine, which is not an inhibitor of PG synthetase, was more effective on the hypocalcemic action than ASP-DL lysine. The phenomenon was observed at the stage especially immediately after intravenous injection, when the acetyl group may be more responsible to acetylate the PG synthetase in the aspirin-DL lysine group. The present results seems to be consistent with the previous hypothesis that PGs are not involved in the process of aspirin-induced hypocalcemia in the rat.

Effects of tolmetin sodium dihydrate on normal and postsurgical peritoneal cell function

Recent studies utilizing intraperitoneal (i.p.) administration of NSAIDs to rabbits after surgical injury to the parietal peritoneum demonstrated macrophage involvement. NSAIDs are known to inhibit the metabolism of arachidonic acid to prostaglandins, which in turn modulate a variety of macrophage functions. Studies presented here examine the effects of tolmetin administration on peritoneal resident and post-surgical leukocyte functions, such as phagocytosis, the release of superoxide anion and tumoricidal activity. Rats, either non-surgical or following peritoneal surgery, were injected i.p. with tolmetin. At various times after treatment, the rats were sacrificed and peritoneal cells collected by lavage. The phagocytic capability of peritoneal leukocytes was transiently decreased 5–7 days after the administration of tolmetin to normal animals. However, administration of tolmetin during surgery extended the lenght of time that phagocytic capability was enhanced. In non-surgical controls, there was an elevation in superoxide anion release and tumoricidal activity 24 h after tolmetin administration. Superoxide anion release was suppressed at days 5 and 7 after treatment, but returned to control levels by day 14. Intraoperative administration of tolmetin significantly elevated superoxide anion release at days 3 and 5, phagocytosis at days 7 and 14 and tumoricidal activity at day 3. These studies suggest that compounds which suppress prostaglandin synthesis can modulate the function of resident and post-surgical peritoneal cells.

Optimization of the in vitro release of zomepirac from suspensions and suppositories

In an in vitro study the release rates of zomepirac acid (I) and zomepirac sodium dihydrate (II) from suspensions in liquid paraffin towards an aqueous phase were determined. When calcium was added to the aqueous phase a cake of zomepiraecalcium was formed at the interface paraffin/buffer and the release rates of I and/or II decreased extensively. The influence of additives, i.e. Tween 80, PVP and lecithin, in the suspension on this caking process was determined. It was found that Tween 80 was the most effective additive. The results obtained were ‘transformed’ to the release of II from suppositories (in vitro studies in a modified Paddle set-up). Again Tween 80 was the most effective additive; the influence of lecithin and PVP was negligible.

Purity determination of zomepirac sodium dihydrate by high-performance liquid chromatography

A high-performance liquid chromatographic method has been developed to determine the purity of zomepirac sodium dihydrate, a novel non-narcotic analgesic agent. This method is sensitive, reproducible, and accurate. The calibration curves are linear over the range of interest for all the related compounds and impurities. A minimum of 0.1% impurity can be easily detected and quantitated.

High-pressure liquid chromatograhic method for surveying the purity of tolmetin sodium dihydrate

High-pressure liquid chromatograhic method for surveying the purity of tolmetin sodium dihydrate