Synthesis and in vitro characterization of chlorpheneramine-laden liposomes for topical applications.

This study was aimed at synthesizing liposomes for the topical delivery of chlorpheneramine maleate using three-level factorial design. Each experiment consisted of a varying proportion of cholesterol, lecithin and a permeation enhancer mixture of Tween80 and polyethylene glycol (PEG1000), and resultant liposomes were extensively characterized. The drug release study was conducted at 6.0 pH, 37±1ºC temperature and 100 rpm rotation speed utilizing a cellophane membrane pouch in a USP type II dissolution apparatus. Among formulations, L5 was considered as the optimal formulation because of high drug loading (99.05%), 87.71% drug release within 4 hours, high drug loading and the optimized formulation was found to be stable during stability testing. This high drug loading and release was achieved at low level of cholesterol and lecithin (0.1: 0.3g) and high level of permeation enhancer mixture (0.2g) as revealed by the surface plots. The drug release from the optimized formulation followed Fickian diffusion as revealed by Korsmeyers-Peppas kinetic model. In summary, combination of PEG1000 and Tween80 with lecithin and cholesterol can be successfully used to develop liposomes that efficiently incorporated chlorpheneramine. This formulation therefore has the potential to be used as a topical anti-allergic product.

Metal-Organic Framework with Dual Active Sites in Engineered Mesopores for Bioinspired Synergistic Catalysis.

Here we report the design of an enzyme-inspired metal-organic framework (MOF), 1-OTf-Ir, by installing strong Lewis acid and photoredox sites in engineered mesopores. Al-MOF (1), with mixed 2,2'-bipyridyl-5,5-dicarboxylate (dcbpy) and 1,4-benzenediacrylate (pdac) ligands, was oxidized with ozone and then triflated to generate strongly Lewis acidic Al-OTf sites in the mesopores, followed by the installation of [Ir(ppy)2(dcbpy)]+ (ppy = 2-phenylpyridine) sites to afford 1-OTf-Ir with both Lewis acid and photoredox sites. 1-OTf-Ir effectively catalyzed reductive cross-coupling of N-hydroxyphthalimide esters or aryl bromomethyl ketones with vinyl- or alkynyl-azaarenes to afford new azaarene derivatives. 1-OTf-Ir enabled catalytic synthesis of anticholinergic drugs Pheniramine and Chlorpheniramine.

Some thoughts about enantioseparations in capillary electrophoresis.

In this overview the goal of the authors was to analyze from the historical perspective the reasons of success and failure of chiral capillary electrophoresis. In addition, the current trends are analyzed, unique advantages of capillary electrophoresis are highlighted and some future directions are discussed.

Electrospinning Optimization of Eudragit E PO with and without Chlorpheniramine Maleate Using a Design of Experiment Approach.

Electrospinning is increasingly becoming a viable means of producing drug delivery vehicles for oral delivery, particularly as issues of manufacturing scalability are being addressed. In this study, electrospinning is explored as a taste-masking manufacturing technology for bitter drugs. The taste-masking polymer Eudragit E PO (E-EPO) was electrospun, guided by a quality by design approach. Using a design of experiment, factors influencing the production of smooth fibers were investigated. Polymer concentration, solvent composition, applied voltage, flow rate, and gap distance were the parameters examined. Of these, polymer concentration was shown to be the only statistically significant factor within the ranges studied ( p-value = 0.0042). As the concentration increased, smoother fibers were formed, coupled with an increase in fiber diameter. E-EPO (35% w/v) was identified as the optimum concentration for smooth fiber production. The optimized processing conditions identified were a gap distance of 175 mm, an applied voltage of between 15 and 20 kV, and a flow rate of 1 mL/h. Using this knowledge, the production optimization of electrospun E-EPO with chlorpheniramine maleate (CPM), a bitter antihistamine drug, was explored. The addition of CPM in drug loads of 1:6 up to 1:10 CPM/E-EPO yielded smooth fibers that were electrospun under conditions similar to placebo fibers. Solid-state characterization showed CPM to be molecularly dispersed in E-EPO. An electronic tasting system, or E-tongue, indicated good taste-masking performance as compared to the equivalent physical mixtures. This study therefore describes a means of producing, optimizing, and assessing the performance of electrospun taste-masked fibers as a novel approach to the formulation of CPM and potentially other bitter drug substances.

Simultaneous determination of kaempferol, quercetin, mangiferin, gallic acid, p-hydroxybenzoic acid and chlorpheniramine maleate in rat plasma after oral administration of Mang-Guo-Zhi-Ke tablets by UHPLC-MS/MS and its application to pharmacokinetics.

Mang-Guo-Zhi-Ke tablets (MGZKTs) is an effective Chinese patent medicine. It contains mango leaf extract as the main raw material and the antihistamine drug, chlorpheniramine maleate is included in the formulation. However, its pharmacokinetic effect is rarely reported. A highly sensitive, reliable and rapid high-throughput method using ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was used to simultaneously determine kaempferol, quercetin, mangiferin, p-hydroxybenzoic acid, gallic acid and chlorpheniramine maleate in rat plasma after oral administration of MGZKTs. The method was successfully developed and fully validated to investigate the pharmacokinetics of MGZKTs. Chloramphenicol and clarithromycin were used as internal standards (IS). A practicable protein precipitation procedure with methanol was adopted for sample preparation. The samples were separated on an Acquity UHPLC Syncronis C18 column (100 × 2.1 mm, 1.7 µm) using 0.1% formic acid-acetonitrile as the mobile phase. The flow rate was set at 0.4 mL/min. The obtained calibration curves were linear in the concentration range of ~1-1000 ng/mL for plasma (r > 0.99). Method validation results met the criteria reported in the US Food and Drug Administration guidelines. Quercetin, p-hydroxybenzoic acid and kaempferol were absorbed rapidly and reached the peak concentration between 0.16 and 0.25 h. This validated that the UHPLC-MS/MS method was successfully applied to study the pharmacokinetic parameters of the six compounds in rat plasma after oral administration of MGZKTs. This evidence will be useful for the clinical rational use of Mang-Guo-Zhi-Ke tablets.

Capillary electrophoretic enantioseparation of basic drugs using a new single-isomer cyclodextrin derivative and theoretical study of the chiral recognition mechanism.

A novel single-isomer cyclodextrin derivative, heptakis {2,6-di-O-[3-(1,3-dicarboxyl propylamino)-2-hydroxypropyl]}-ß-cyclodextrin (glutamic acid-ß-cyclodextrin) was synthesized and used as a chiral selector in capillary electrophoresis for the enantioseparation of 12 basic drugs, including terbutaline, clorprenaline, tulobuterol, clenbuterol, procaterol, carvedilol, econazole, miconazole, homatropine methyl bromide, brompheniramine, chlorpheniramine and pheniramine. The primary factors affecting separation efficiency, which include the background electrolyte pH, the concentration of glutamic acid-ß-cyclodextrin and phosphate buffer concentration, were investigated. Satisfactory enantioseparations were obtained using an uncoated fused-silica capillary of 50 cm (effective length 40 cm) × 50 µm id with 120 mM phosphate buffer (pH 2.5-4.0) containing 0.5-4.5 mM glutamic acid-ß-cyclodextrin as background electrolyte. A voltage of 20 kV was applied and the capillary temperature was kept at 20°C. The results proved that glutamic acid-ß-cyclodextrin was an effective chiral selector for studied 12 basic drugs. Moreover, the possible chiral recognition mechanism of brompheniramine, chlorpheniramine and pheniramine on glutamic acid-ß-cyclodextrin was investigated using the semi-empirical Parametric Method 3.

Physicochemical properties and mechanisms of drug release from melt-extruded granules consisting of chlorpheniramine maleate and Eudragit FS.

The objective of this research project was to characterize the drug release profiles, physicochemical properties and drug-polymer interaction of melt-extruded granules consisting of chlorpheniramine maleate (CPM) and Eudragit® FS. Melt extrusion was performed using a single screw extruder at a processing temperature of 65-75 °C. The melt extrudate was milled, blended with lactose monohydrate and then filled into hard gelatin capsules. Each capsule contained 300 mg CPM granules. The release of CPM was determined with the United States Pharmacopeia dissolution apparatus II using a three-stage dissolution medium testing in order to simulate the pH conditions of the gastrointestinal tract. Pore structure, thermal properties and surface morphologies of CPM granules were studied using mercury and helium pycnometer, differential scanning calorimeter and scanning electron microscope. Sustained release of CPM over 10 h was achieved. The release of CPM was a function of drug loading and the size of the milled granules. The complexation between CPM and Eudragit® FS as the result of counterion condensation was observed, and the interaction was characterized using membrane dialysis and H(1) NMR techniques. In both 0.1 N HCl and phosphate buffer pH 6.8, CPM was released via a diffusion mechanism and the release rate was controlled by the pore structure of the melt-extruded granules. In phosphate buffer pH 7.4, CPM release was controlled by the low pH micro-environment created by CPM, the pore structure of the granules and the in situ complexation between CPM and Eudragit® FS.

Development and validation of a sensitive UHPLC-MS/MS method for the simultaneous analysis of tramadol, dextromethorphan chlorpheniramine and their major metabolites in human plasma in forensic context: application to pharmacokinetics.

The prerequisites for forensic confirmatory analysis by LC/MS/MS with respect to European Union guidelines are chromatographic separation, a minimum number of two MS/MS transitions to obtain the required identification points and predefined thresholds for the variability of the relative intensities of the MS/MS transitions (MRM transitions) in samples and reference standards. In the present study, a fast, sensitive and robust method to quantify tramadol, chlorpheniramine, dextromethorphan and their major metabolites, O-desmethyltramadol, dsmethyl-chlorpheniramine and dextrophan, respectively, in human plasma using ibuprofen as internal standard (IS) is described. The analytes and the IS were extracted from plasma by a liquid-liquid extraction method using ethyl acetate-diethyl-ether (1:1). Extracted samples were analyzed by ultra-high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Chromatographic separation was performed by pumping the mobile phase containing acetonitrile, water and formic acid (89.2:11.7:0.1) for 2.0 min at a flow rate of 0.25 µL/min into a Hypersil-Gold C18 column, 20 × 2.0 mm (1.9 µm) from Thermoscientific, New York, USA. The calibration curve was linear for the six analytes. The intraday precision (RSD) and accuracy (RE) of the method were 3-9.8 and -1.7-4.5%, respectively. The analytical procedure herein described was used to assess the pharmacokinetics of the analytes in 24 healthy volunteers after a single oral dose containing 50 mg of tramadol hydrochloride, 3 mg chlorpheniramine maleate and 15 mg of dextromethorphan hydrobromide.

Evaluation of Prosopis africana Seed Gum as an Extended Release Polymer for Tablet Formulation.

In the present work, an attempt has been made to screen Prosopis africana seed gum (PG), anionic polymer for extended release tablet formulation. Different categories of drugs (charge basis) like diclofenac sodium (DS), chlorpheniramine maleate (CPM), and ibuprofen (IB) were compacted with PG and compared with different polymers (charge basis) like xanthan gum (XG), hydroxypropyl methyl cellulose (HPMC-K100M), and chitosan (CP). For each drug, 12 batches of tablets were prepared by wet granulation technique, and granules were evaluated for flow properties, compressibility, and compactibility by Heckel and Leuenberger analysis, swelling index, in vitro dissolution studies, etc. It has been observed that granules of all batches showed acceptable flowability. According to Heckel and Leuenberger analysis, granules of PG-containing compacts showed similar and satisfactory compressibility and compactibility compared to granules of other polymers. PG showed significant swelling (P < 0.05) compared to HPMC, and better than CP and XG. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) study showed no interaction between drugs and polymers. From all PG-containing compacts of aforesaid drugs, drug release was sustained for 12 h following anomalous transport. Especially, polyelectrolyte complex formation retarded the release of oppositely charged drug (CPM-PG). However, extended release was noted in both anionic (DS) and nonionic (IB) drugs, maybe due to swollen gel. All compacts were found to be stable for 3-month period during stability study. This concludes that swelling and release retardation of PG has close resemblance to HPMC, so it can be used as extended release polymer for all types of drugs.

Pepsin-modified chiral monolithic column for affinity capillary electrochromatography.

Pepsin-modified affinity monolithic capillary electrochromatography, a novel microanalysis system, was developed by the covalent bonding of pepsin on silica monolith. The column was successfully applied in the chiral separation of (±)-nefopam. Furthermore, the electrochromatographic performance of the pepsin-functionalized monolith for enantiomeric analysis was evaluated in terms of protein content, pH of running buffer, sample volume, buffer concentration, applied voltage, and capillary temperature. The relative standard deviation (%RSD) values of retention time (intraday <0.53, n = 10; interday <0.53, n = 10; column-to-column <0.70, n = 20; and batch-to-batch <0.80, n = 20) indicated satisfactory stability of these columns. No appreciable change was observed in retention and resolution for chiral recognition of (±)-nefopam in 50 days with 100 injections. The proteolytic activity of this stationary phase was further characterized with bovine serum albumin as substrate for online protein digestion. As for monolithic immobilized enzyme reactor, successive protein injections confirmed both the operational stability and ability to reuse the bioreactor for at least 20 digestions. It implied that the affinity monolith used in this research opens a new path of exploring particularly versatile class of enzymes to develop enzyme-modified affinity capillary monolith for enantioseparation.

Simultaneous quantitative analysis of dextromethorphan, dextrorphan and chlorphenamine in human plasma by liquid chromatography-electrospray tandem mass spectrometry.

A sensitive and accurate HPLC-MS/MS method was developed for the simultaneous determination of dextromethorphan, dextrorphan and chlorphenamine in human plasma. Three analytes were extracted from plasma by liquid-liquid extraction using ethyl acetate and separated on a Kromasil 60-5CN column (3 µm, 2.1 × 150 mm) with mobile phase of acetonitrile-water (containing 0.1% formic acid; 50:50, v/v) at a flow rate of 0.2 mL/min. Quantification was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. The calibration curve was linear over the range of 0.01-5 ng/mL for dextromethorphan, 0.02-5 ng/mL for dextrorphan and 0.025-20 ng/mL for chlorphenamine. The lower limits of quantification for dextromethorphan, dextrorphan and chlorphenamine were 0.01, 0.02 and 0.025 ng/mL, respectively. The intra- and inter-day precisions were within 11% and accuracies were in the range of 92.9-102.5%. All analytes were proved to be stable during sample storage, preparation and analytic procedures. This method was first applied to the pharmacokinetic study in healthy Chinese volunteers after a single oral dose of the formulation containing dextromethorphan hydrobromide (18 mg) and chlorpheniramine malaeate (8 mg).

Potential use of a megamolecular polysaccharide sacran as a hydrogel-based sustained release system.

A megamolecular polysaccharide sacran was newly extracted from cyanobacterium Aphanothece sacrum. Sacran has many preferable properties for transdermal application, e.g. a safe biomaterial, a high moisturizing effect, a formation of film and hydrogel. Additionally, it was recently discovered that sacran has an anti-inflammatory effect for atopic dermatitis model mice. In this study, in order to evaluate the feasibility of sacran-hydrogel as a novel sustained release system, we prepared a sacran-hydrogel containing 4-biphenyl acetic acid (BPAA, an acidic drug), prednisolone (PD, a neutral drug) or chlorpheniramine maleate (CPM, a basic drug), and performed the in vitro release studies. The sacran-hydrogel containing BPAA, PD or CPM provided a sustained release profile in accordance with a quasi-Fickian diffusion model. Furthermore, the release rate of drugs from sacran-hydrogels can be controlled by adjusting the concentration of aluminum chloride as a cross linker. These results suggest the potential use of sacran-hydrogel as a sustained release system for drugs.

Evaluation of Chlorpheniramine Maleate microparticles in orally disintegrating film and orally disintegrating tablet for pediatrics.

OBJECTIVE: To mask the bitterness of Chlorpheniramine Maleate via encapsulating drug into Eudragit EPO microparticles, and then incorporate these microparticles into orally disintegrating films (ODF) and orally disintegrating tablets (ODT) for pediatric uses. METHODS: Spray drying of water-in-oil emulsion was utilized to encapsulate Chlorpheniramine Maleate into Eudragit EPO microparticles. Based on an orthogonal experimental design L9 (3(3)), polynomial regression models were developed to evaluate correlation between microparticle properties (encapsulation efficiency and drug release) and variables (X1: weight ratio of polymer to drug, X2: volume ratio of oil to water and X3: Q-flow of spray dryer). ODF and ODT formulations were evaluated including weight variation, content uniformity, tensile strength, disintegration time, friability and dissolution profiles. The bitterness taste test was evaluated in 10 adult volunteers. RESULTS AND DISCUSSION: From polynomial regression analysis, the best values of variables leading to the optimized microparticles were X1 = 10, X2 = 3 and X3 = 45. The optimized microparticles were incorporated into ODF and ODT with satisfactory weight and drug content uniformity, and acceptable physical strength. Both dosage forms disintegrated immediately (less than 40 s) in simulated saliva solutions. The outcome of taste-masking test indicated that microparticles alleviated drug bitterness significantly; bitterness was not discernible with microparticles incorporated in ODT, whereas only slight bitterness was detected from microparticles incorporated into ODF. CONCLUSION: Both ODF and ODT are shown to be suitable vehicles for taste masked Chlorpheniramine Maleate microparticles with potential for pediatric uses.

Development of a novel UPLC approach to co-prediction of four active compounds in a multi-component pharmaceutical preparation.

In this work, a new ultra-performance liquid chromatography method based on photodiode array detection (UPLC-PDA) was first developed for the quantitative analysis of the quaternary mixture of ascorbic acid (AA), paracetamol (PAR), caffeine (CAF) and chlorpheniramine maleate (CPA) in a commercial dosage form. The developed UPLC-PDA method offered a new possibility for the co-determination of four active ingredients in a drug combination with short run time and simple sample preparation. The successful chromatographic separation of the four drugs was performed using a Waters Acquity UPLC BEH C18 column (1.7 µm 2.1 × 100 mm) (Mildford, USA) and a mobile phase consisting of water (12 %), acetonitrile (13 %) and 0.1 M H3PO4 (75 %) at a flow rate of 0.25 mL/min. The validation of the proposed UPLC-PDA approach was verified by analyzing synthetic mixtures, inter- and intra-day experiments, and commercial powder samples and provided satisfactory results.

Formulation and development of taste masked fast-disintegrating tablets (FDTs) of Chlorpheniramine maleate using ion-exchange resins.

CONTEXT: Masking of bitter taste of drug for better patient compliance. OBJECTIVE: The objective of this research was to mask the bitter taste of Chlorpheniramine maleate using cation exchange resins. MATERIALS AND METHODS: Different cation exchange resins were used for taste masking. The drug resin complexes (DRC) were prepared by batch process. Complexes of ion-exchange resin and Chlorpheniramine maleate were prepared by taking drug: resin ratios 1:1, 1:2, 1:3 and 1:4 (w/w). The optimum drug:resin ratio and the time required for maximum complexation was determined. The drug resinates were evaluated for the drug content, taste, drug release, FTIR, DSC and X-ray diffraction (PXRD). RESULTS AND DISCUSSION: The X-ray diffraction study confirmed the monomolecularity of entrapped drug in the resin beads. The taste evaluation depicted the successful taste masking of Chlorpheniramine maleate with DRCs. Fast disintegrating tablets (FDTs) were developed depending upon percent complexation, release study at salivary and gastric pH, taste evaluation; Chlorpheniramine maleate: Indion-234 complex of ratio 1:2 was used to develop and formulate FDTs. The drug release of 94.77% in 30 min was observed from FDTs. CONCLUSION: The Effective taste masking can be obtained from DRC that can be formulated as FDTs for better patient compliance.

Report: Simultaneous determination of naphazoline hydrochloride, chlorpheniramine maleate and methylene blue in their ternary mixture.

Validated spectrophotometric and chemometric methods were developed for determination of Naphazoline Hydrochloride (NAP), Chlorpheniramine maleate (CLO) and Methylene blue (MB) in their ternary mixture. Method A was a spectrophotometric method, where NAP and MB were determined using second derivative (D²) spectrophoto metric method using the peak amplitudes at 299 nm and 337 nm for NAP and MB respectively , while CLO was determined using second derivative ratio (DD²) spectrophotometric method using the peak amplitude at 276.6 nm. Method B used the chemometric techniques; principal component regression (PCR) and partial least squares (PLS) for determination of NAP, CLO and MB using the information contained in the absorption spectra of their ternary mixture solutions. The proposed methods have been successfully applied for the analysis of NAP, CLO and MB in their pharmaceutical formulation and the obtained results were statistically compared with the reported methods.

Pharmacophore modeling for hERG channel facilitation.

Human ether-a-go-go-related gene (hERG) channels play a critical role in cardiac action potential repolarization. The unintended block of hERG channels by compounds can prolong the cardiac action potential duration and induce arrhythmia. Several compounds not only block hERG channels but also enhance channel activation after the application of a depolarizing voltage step. This is referred to as facilitation. In this study, we tried to extract the property of compounds that induce hERG channel facilitation. We first examined the facilitation effects of structurally diverse hERG channel blockers in Xenopus oocytes. Ten of 13 assayed compounds allowed facilitation, suggesting that it is an effect common to most hERG channel blockers. We constructed a pharmacophore model for hERG channel facilitation. The model consisted of one positively ionizable feature and three hydrophobic features. Verification experiments suggest that the model well describes the structure-activity relationship for facilitation. Comparison of the pharmacophore for facilitation with that for hERG channel block showed that the spatial arrangement of features is clearly different. It is therefore conceivable that two different interactions of a compound with hERG channels exert two pharmacological effects, block and facilitation.

An approach to formulating an oral floating drug delivery system for dexchlorpheniramine maleate using factorial design.

The purpose of this research was to formulate and evaluate a floating tablet formulation of dexchlorpheniramine maleate (DCPM) using full factorial design. A 32 factorial design (nine runs) was utilized to optimize the formulation, the contents of hydroxypropyl methyl cellulose (HPMC) (X1) and Carbopol 934P (X2) being taken as independent variables and t50% (Y1), % drug release after 6 h (Y2), % drug release after 12 h (Y3), and floating lag time (FLT) (Y4) as the dependent variables. The tablets showed 99.2635 to 102.4709 of the labeled amount of dexchlorpheniramine maleate indicating uniformity of content. The tablets containing DCPM released 72.28 to 99.461% of drug at the end of 12 h by an in vitro release study. Hardness, friability, floating capacity, weight variation and content uniformity were also examined. In addition,the tablets were evaluated for in vitro release characteristics for 24 h. The optimal batch (F9) was selected by regression analysis and followed Higuchi kinetics. The drug release mechanism was found to be a complex mixture of diffusion, swelling and erosion. The floating tablets of DCPM developed may be used clinically for prolonged drug release for at least 16 hrs, thereby improving bioavailability and patient compliance.

Preparation and in vitro release of dual-drug resinate complexes containing codeine and chlorpheniramine.

OBJECTIVE: To develop the dual-drug resinate complexes containing codeine and chlorpheniramine with a novel batch processing, characterize the dual-drug resinate complexes, and study its drug release behavior in vitro. METHODS: A procedure of simultaneous dual-drug loading using combination solutions composed of different proportions of codeine phosphate and chlorpheniramine maleate was performed to achieve the specific resinate, and the dual-drug loading content was determined by high-performance liquid chromatography method. The dual-drug resinate complexes were characterized by a scanning electron microscope, and the formation mechanisms were confirmed with X-ray diffraction analyses and differential scanning calorimetric analyses. The release behavior of the two drugs from the dual-drug resinate complexes in vitro was studied in the media simulating in vivo environments (simulated gastric fluid: pH = 1.2 HCl, simulated in vivo ionic strength: 0.15 M NaCl, and simulated intestinal fluid: pH = 6.8 buffer solution containing KH2PO4-NaOH). RESULTS: Scanning electron microscopic analyses proved that the dual-drug resinate complexes had the same appearance and characters as the initiative ion exchange resins (IERs). Via X-ray diffraction and differential scanning calorimetric analyses, it is found that the two drugs in dual-drug resinate complexes were combined with IERs by chemical bond. The drug-resinate complex, like IER, was in amorphous state. More than 90% of codeine phosphate was released in 15 minutes in three different media, whereas little amount of chlorpheniramine maleate was released in all the release time in the medium pH = 1.2 HCl, and the release equilibrium time was about 5 minutes, only 40% was released in the medium 0.15 M NaCl, and the equilibrium time was 40 minutes, and about 90% was released in the medium pH = 6.8 KH2PO4-NaOH. The increased ionic strength generally accelerated the release of the two drugs from the dual-drug resinate complexes. CONCLUSION: The dual-drug resinate complexes were formed through the reaction between the drugs and the IERs by chemical bond. The release behavior of the drug from the dual-drug resinate complexes in vitro was mainly correlated with the drug molecular structure, the eluting ionic strength, composition, and ionic strength of the release media. The novel dual-drug resinate complexes could be used to deliver two drugs in one therapeutic dose.

Use of cyclodextrin-modified gold nanoparticles for enantioseparations of drugs and amino acids based on pseudostationary phase-capillary electrochromatography.

The application of chemical-modified gold nanoparticles (GNPs) as chiral selector for the enantioseparation based on pseudostationary phase-CEC (PSP-CEC) is presented. GNPs modified by thiolated beta-CD were characterized by NMR and FT-IR. The nanoparticle size was determined to be of 9.5 nm (+2.5 nm) by Transmission Electron Microscopy (TEM) and UV spectra. Four pairs of dinitrophenyl-labeled amino acid enantiomers (DL-Val, Leu, Glu and Asp) and three pairs of drug enantiomers (RS-chlorpheniramine, zopiclone and carvedilol) were analyzed by using modified GNPs as the chiral selector in PSP-CEC. Good theoretical plate number (up to 2.4x10(5) per meter) and separation resolution (up to 4.7) were obtained even with low concentration of modified GNPs (0.8-1.4 mg/mL). The corresponding concentration of beta-CD in the buffer was only 0.30-0.53 mM, which was much lower than the optimum concentration of 15 mM if pure beta-CD was used as chiral selector. Our results showed that thiolated beta-CD modified GNPs have more sufficient interaction with the analytes, resulting in significant enhancement of enantioseparation. The study shed light on potential usage of chemical modified GNPs as chiral selector for enantioseparation based on PSP-CEC.