A pH-responsive drug delivery matrix from an interpolyelectrolyte complex: preparation and pharmacotechnical properties

ABSTRACT Interpolyelectrolyte complexes, which constitute a type of polymeric material obtained through the self-assembly of oppositely charged polymers, exhibit interesting properties for use in the design of smart matrices for drug delivery. In the present study, a stoichiometric interpolyelectrolyte complex (SIPEC) composed of Eudragit E® and Eudragit® L100 was obtained at pH 6.0 and characterized and evaluated as a hydrophilic matrix for dexibuprofen. The formation of a SIPEC was monitored by ζ-potential measurements and characterized using infrared spectroscopy, thermal analysis, and scanning electron microscopy. The results indicated that a SIPEC obtained under these conditions can be used as a matrix for controlling the release of dexibuprofen and exhibit a pH-triggered release

Safety pharmacology research on Dexibuprofen injection / 药物评价研究

Objective To study the effects of Dexibuprofen injection on the central nervous,cardiovascular and respiratory systems in animals.Methods The effect of Dexibuprofen injection on central nervous system was observed by autonomic activities experiment,mice concordant ability experiment and hypnotize experiment induced by pentobarbital.The effects of Dexibuprofen injection on circulatory system and respiratory system were observed by measuring the implanted telemetry system,blood pressure,ECG;respiratory rate and tidal volume of Beagle's dogs.Results Dexibuprofen injection (80 mg/kg) showed synergistic action with pentobarbital,and no significant effects on autonomic activities and concordant ability at doses of 20,40 and 80 mg/kg in mice.Dexibuprofen injection at doses of 10,20 and 40 mg/kg had no effect on the central nervous,cardiovascular and respiratory systems.In the same dose,the adverse reaction of Dexibuprofen injection was not increased compared with Ibuprofen injection.Conclusion Dexibuprofen injection (mice 40 mg/kg,dog 40 mg/kg) has none toxicity on cardiovascular,respiratory and central nervous systems,but at the dose of 80 mg/kg in mice has obvious effect on central nervous system.

Determination of Related Substances in Dexibuprofen and Its Sustained Release Tablets by HPLC / 中国药师

Objective:To determine the related substances in dexibuprofen and its sustained release tablets by HPLC .Methods:The related substances including a-methyl-4-butyl benzene acetic acid , L-ibuprofen and the others were detected by HPLC .An Agilent Eclipse XDB-C18 column (150 mm ×4.6 mm, 5 μm) was used for a-methyl-4-butyl benzene acetic acid and the other related sub-stances.A Kromasil 5-TBB column (250 mm ×4.6 mm, 5 μm) was used for L-ibuprofen.The mobile phases was acetonitrile and phosphate solution (45 ∶55, pH value was adjusted to 2.5 by phosphoric acid), hexane-tert-butyl ether-acetic acid (850 ∶150 ∶1), acetonitrile and sodium acetate buffer (60 ∶40, 6.13g sodium acetate was dissolved in 750ml water, and pH was adjusted to 2.5 by glacial acetic acid ) , respectively .The detection wavelength was 214 nm, 220 nm and 263 nm, respectively .The flow rate for a-meth-yl-4-butyl benzene acetic acid and the other related substances was 1.0 ml· min-1 .The flow rate for L-ibuprofen was 2.0 ml· min-1 . The column temperature was 30℃and the injection volume was 20 μl.Results:The method could effectively detect the contents of a-methyl-4-butyl-phenylacetic acid and L-ibuprofen, and identify and separate the related substances in dexibuprofen raw material and its sustained release tablets .Conclusion:The method is specific , accurate and easy to operate , which can be used for the quality control of ibuprofen raw material and its sustained release tablets .

Preparation of Dexibuprofen Sustained-release Pellets and Analysis on Drug Release Behavior / 中国药房

OBJECTIVE:To prepare dexibuprofen sustained-release pellets,and to analyze the drug release behavior in vitro. METHODS:Centrifugal granulation powder layering-eudragit dispersion coating method was used to prepare dexibuprofen sus-tained-release pellets using 3%HPMC as adhesive agent. The formula of the pellets was optimized by orthogonal test with weight ra-tio of sucrose to dexibuprofen,weight ratio of HPMC to Eudragit NE30D and coating weight as factors,using 1,4 and 10 h accu-mulated release rate (Q) as index. The release of the drug from the pellets was analyzed. RESULTS:The optimized formulation was that the proportion of sucrose to drug was 1:10,the weight ratio of HPMC to Eudragit NE30D was 1.5:1,the increased weight of coating material was 8%. Q1 h,Q4 h and Q10 h of prepared pellets were 21%,57% and 89%,respectively(n=3). The co-rrelation coefficient of zero-order,one-order and Higuchi equation release model were 0.956 6,0.989 9,0.996 5. CONCLUSIONS:Prepared pellets show good sustained-release effect in vitro. Drug release of pellets is more in accordance with Higuchi equation.

Comparative Effect of Antidepressants (Duloxetine) and NSAID (Dexibuprofen) in a New Rat Model of Chronic Pain Induced Depression Associated with Monosodium Iodo Acetate (MIA) Induced Osteoarthritis in Rats.

Objective: To evaluate the role of anti-depressants (Duloxetine) and NSAID (Dexibuprofen) in a new rat model of chronic induced depression. Methods: Twenty four male wistar rats were divided into 4 groups of 6 animals each. Group I to IV served as vehicle control, osteoarthritis (OA) control, duloxetine and dexibuprofen treated groups respectively. Group I received intra-articular Injection of 50 μl of 0.9% normal saline, and Group II to IV received 50 μl MIA, and the treatment of drugs started on the same day. The animals will be monitored for OA parameters and/or depression on pre-dose day (day 0) and on day 1, 3, 5, 7, 11, 14, 18, 21 and 28 th day. Results and Discussion: In MIA treated group, the rise in knee inflammation is maximum on day 3 (12.31±0.85 mm; p<0.001) and reduced near to normal on day 7 (9.26±0.57 mm; p<0.001). Dexibuprofen and duloxetine decreased the inflammation from day 3, and the decrease is comparatively better in dexibuprofen group. Also, dexibuprofen increased vocalization threshold of knee compression force for 7 days and decreased thereafter, whereas duloxetine has no effect for first 7 days and increased thereafter. Duloxetine was significantly (p<0.001) effective on neuropathic pain (Punctate allodynia, mechanical gripstrength, threshold angle of knee extension) and depression (forced swim test and locomotor activity) compared to dexibuprofen. Conclusion: The present study has shown that dexibuprofen has the potential in the initial phase of chronic OA and duloxetine in the later stage, where neuropathic and depressive component dominates.

Pharmacokinetics of dexibuprofen in rats after oral administration of dexibuprofen and dexibuprofen arginate / 中国药学杂志

OBJECTIVE: To establish an HPLC-MS/MS method for the determination of dexibuprofen in rat plasma and to study the pharmacokinetic profiles of dexibuprofen in rats after oral administration of dexibuprofen suspention or dexibuprofen arginate aqueous solution. METHODS: Dexibuprofen suspention or dexibuprofen arginate aqueous solution was administered orally as a single dose to rats. Blood was collected at different time points and blood samples were prepared by protein precipitation. The concentration of dexibuprofen in plasma was determined by an HPLC-MS/MS method using indomethacin as internal standard. RESULTS: The oral administration of both dexibuprofen suspention and dexibuprofen arginate aqueous solution resulted in rapid absorption of dexibuprofen. The AUC of dexibuprofen after oral administration of dexibuprofen arginate aqueous solution in rats was significantly higher than the ALC of dexibuprofen after administration of dexibuprofen suspention at equivalent dose. CONCLUSION: Dexibuprofen will show an enhancement in oral bioavailability in the salt formulation as dexibuprofen arginate. Copyright 2012 by the Chinese Pharmaceutical Association.

Preparation and Quality Control of Dexibuprofen Syrup / 中国药房

OBJECTIVE:To prepare Dexibuprofen Syrup and establish a method for its quality control.METHODS:Dexibuprofen Syrup was prepared with dexibuprofen as main ingredient and the content of dexibuprofen was determined by HPLC.RESULTS:The preparation appeared as yellowish or yellowish-brown sticky liquid and its property was in line with the standard specified in Chinese Pharmacopeia(2005 Edition).The linear range of dexibuprofen was 0.100 6～0.502 8 mg?mL-1(r=0.999 9)and its average recovery rate was 99.65%(RSD=0.64%).CONCLUSION:This preparation is simple and feasible in preparation technology and controllable in quality.