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Basic Drugs (basic + drug)
Selected AbstractsSeparation of Basic Drugs Using Pressurized Capillary ElectrochromatographyCHINESE JOURNAL OF CHEMISTRY, Issue 4 2003Zhang Kai Abstract A novel pressurized capillary electrochromatography (PCEC) was developed to separate basic drugs on strong cation exchange (SCX) column. The separation result by using PCEC was better than that by using micro-HPLC. The effects of electrical field and pressure on plate height and resolution were investigated. Influence of organic modifier, ionic strength and pH value of buffer on retention behavior were evaluated, and the separation mechanism was also discussed. [source] Investigation of some factors contributing to negative food effectsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2009Venugopal P. Marasanapalle Abstract A drug is defined as exhibiting negative food effects, if the co-administration of food statistically decreases its area under the curve, AUC, when compared with its administration on a fasted stomach. In this study, the role of biopharmaceutical factors that contribute to negative food effects was studied using furosemide, nadolol, tacrine and atenolol (as model compounds exhibiting negative food effects), and prednisolone, hydrochlorothiazide and ibuprofen (as model compounds that do not show any food effects). The physiological pH of the upper intestinal tract is lower, at pH 5, in the postprandial state when compared with the preprandial state, pH 6.5. Drugs that exhibited negative food effects had low apical to basolateral Caco-2 permeabilities, low pKa/pKb and Log P values of less than 1. The drugs exhibiting negative food effects had low distribution coefficients at the pH conditions of the fed and fasted states. Furosemide, being a hydrophilic, poorly soluble acidic drug showed lower solubility in the fed state when compared with the fasted state. Basic drugs, atenolol, nadolol and tacrine, are ionized to a higher extent in the fed state and exhibit lower permeability and lower absorption when compared with the fasted state. Thus, drugs were found to exhibit negative food effects owing to their decrease in solubility or permeability in the upper intestinal tract of the fed state when compared with the fasted state. Copyright © 2009 John Wiley & Sons, Ltd. [source] Characterization of basic drug,human serum protein interactions by capillary electrophoresisELECTROPHORESIS, Issue 17 2006María A. Martínez-Gómez Abstract Drug,protein interactions are determining factors in the therapeutic, pharmacodynamic and toxicological drug properties. The affinity of drugs towards plasmatic proteins is apparently well established in bibliography. Albumin (HSA) especially binds neutral and negatively charged compounds; ,1 -acid glycoprotein,(AGP) binds many cationic drugs, lipoproteins bind to nonionic and lipophilic drugs and some anionic drugs while globulins interact inappreciably with the majority of drugs. In this paper, the characterization of the interaction between cationic drugs, ,-blockers and phenotiazines towards HSA, AGP, and both HSA + AGP mixtures of proteins under physiological conditions by CE-frontal analysis is presented. Furthermore, the binding of these drugs to all plasmatic proteins is evaluated by using ultrafiltration and CE. The results indicate that the hydrophobic character of compounds seems to be the key factor on the interaction between cationic drugs towards proteins. In fact, hydrophobic basic drugs bind in great extension to HSA, while hydrophilic basic drugs present low interactions with proteins and bind especially to AGP. [source] Microenvironmental pH modulation in solid dosage formsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2007Sherif I. Farag Badawy Abstract There are many reports in the literature referring to the effect of ,microenvironmental pH' on solid dosage form performance, particularly stability and dissolution profiles. Several techniques have been proposed for the measurement of the microenvironmental pH. Those techniques use certain assumptions and approximations and many of them employ a solution calibration curve of a probe to predict hydrogen ion activity in a substantially dry solid. Despite the limitation of the methodology, it is clear from the literature that microenvironmental pH has a significant impact on stability of compounds which demonstrate pH dependent stability in solution. Degradation kinetics of such compounds, and in some cases degradation profile as well, are dependent on the microenvironmental pH of the solid. Modulation of the microenvironmental pH through the use of pH modifiers can hence prove to be a very effective tool in maximizing solid dosage form stability. Judicial selection of the appropriate pH modifier, its concentration and the manufacturing process used to incorporate the pH modifier is necessary to enhance stability. Control of microenvironmental pH to maximize stability can be achieved without the use of pH modifier in some cases if an appropriate counter ion is used to provide an inherently optimal pH for the salt. Microenvironmental pH modulation was also shown to control the dissolution profile of both immediate and controlled release dosage forms of compounds with pH dependent solubility. The pH modifiers have been used in conjunction with high energy or salt forms in immediate release formulations to minimize the precipitation of the less soluble free form during initial dissolution. Additionally, pH modifiers were utilized in controlled release dosage forms of weakly basic drugs which exhibit diminished release in dissolution media with high pH. The incorporation of acidic pH modifiers in the controlled release formulation increases the solubility of the basic drug even as the high pH dissolution medium enters into the dosage form hence increasing drug release rate. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 948,959, 2007 [source] Investigation of drug,porous adsorbent interactions in drug mixtures with selected porous adsorbentsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2007Shadi Madieh Abstract The adsorption of drugs onto porous substrates may prove to be a convenient method by which to enhance the dissolution rate of certain poorly water-soluble drugs in body fluids. The purpose of this research is to provide a better understanding of the type of interactions occurring between drugs and certain pharmaceutically acceptable porous adsorbents that leads to enhanced drug dissolution rates. The interactions between ibuprofen (acidic drug), acetaminophen (acidic drug), dipyridamole (basic drug), and the porous adsorbents used (calcium silicate and silica gel) were investigated using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier Transform infrared spectroscopy (FTIR). DSC and PXRD results indicated a significant loss of crystallinity of both ibuprofen and acetaminophen but not dipyridamole. In the case of ibuprofen, FTIR results indicated the ionization of the carboxylic group based on the shift in the FTIR carboxylic band. Dissolution of ibuprofen from its mixtures with porous adsorbents was found to be significantly higher compared to the neat drug, whereas dipyridamole dissolution from its mixtures with porous adsorbents was not significantly different from that of the neat drug. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 851,863, 2007 [source] Effect of chloride ion on dissolution of different salt forms of haloperidol, a model basic drugJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2005Shoufeng Li Abstract The effect of chloride ion (Cl,) on dissolution rates of hydrochloride, mesylate (methanesulfonate) and phosphate salt forms of a model drug, haloperidol, was investigated. The dissolution rates of the salts in 0.01M HCl from rotating disks followed the order of mesylate,,,phosphate,>,hydrochloride. With additional chloride ion, a decrease in dissolution rate of the hydrochloride salt was observed due to the common ion effect. Dissolution rates of mesylate and phosphate salts also decreased due to their conversion to the HCl salt form on the surfaces of dissolving disks, however, the dissolution rates of mesylate and phosphate salts under identical chloride ion concentrations were still higher than that of the HCl salt. In powder dissolution studies, it was observed that kinetics of nonhydrochloride-to-hydrochloride salt conversion play a major role in dissolution; the mesylate dissolved completely (<5 min) before its dissolution rate could be impeded by its conversion to the hydrochloride salt form. Therefore, despite the potential for conversion to a hydrochloride salt form, certain nonhydrochloride salt forms may still be preferred for dosage form development due to kinetic advantages during dissolution, such as higher apparent dissolution rate of a nonhydrochloride salt before it could completely convert to the hydrochloride form. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2224,2231, 2005 [source] Chiral analysis of milnacipran by a nonchiral HPLC , circular dichroism: Improvement of the linearity of dichroic response by temperature controlJOURNAL OF SEPARATION SCIENCE, JSS, Issue 16-17 2008Marie Lecoeur-Lorin Abstract The determination of the enantiomeric excess (e.e.) of a basic drug has been investigated in LC using a nonchiral stationary phase and a circular dichroism (CD) detector in order to avoid expensive chiral columns. The CD detector records both dichroic (,,) and UV (,) signals at the same wavelength and calculates the anisotropy factor (g = ,,/,), which is linearly related to the e.e. The enantiomeric and chemical composition of a chiral drug can be simultaneously determined on a nonchiral HPLC support. However, the g factor from the CD signal is temperature dependent. Indeed, the temperature has an influence on the stability of the CD signal and the linear regression between g factor and the e.e. of 1R,2S -enantiomer. So, a decrease in temperature gives rise to an improvement of the above-mentioned linearity correlation. After optimization of chromatographic parameters (porous graphitic carbon-based column, methanol/ phosphate buffer as mobile phase) and selection of CD wavelength, a linear regression of g factor versus e.e. of 1R,2S -enantiomer was obtained at temperature-controlled CD detection and an LOQ of 94% was found. The enantiomeric composition of milnacipran was determined with good accuracy. [source] A simplified protein precipitation/mixed-mode cation-exchange solid-phase extraction, followed by high-speed liquid chromatography/mass spectrometry, for the determination of a basic drug in human plasmaRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2006Y.-J. Xue A simplified protein precipitation/mixed-mode cation-exchange solid-phase extraction (PPT/SPE) procedure has been investigated. A mixture of acetonitrile and methanol along with formic acid was used to precipitate plasma proteins prior to selectively extracting the basic drug. After vortexing and centrifugation, the supernatants were directly loaded onto an unconditioned Oasis® MCX µElution 96-well extraction plate, where the protonated drug was retained on the negatively charged sorbent while interfering neutral lipids, steroids or other endogenous materials were washed away. Normal wash steps were deemed unnecessary and not used before sample elution. The sample extracts were analyzed under both conventional and high-speed liquid chromatography/tandem mass spectrometry (LC/MS/MS) conditions to examine the feasibility of the PPT/SPE procedure for human plasma sample clean-up. For the conventional LC/MS/MS method, chromatographic separation was achieved on a C18, 2.1,×,50,mm column with gradient elution (k,,=,5.5). The mobile phase contained 0.1% formic acid in water and 0.1% formic acid in acetonitrile. For the high-speed LC/MS/MS method, chromatographic separation was achieved on a C18, 2.1,×,10,mm guard column with gradient elution (k,,=,2.2, Rt,=,0.26,min). The mobile phase contained 0.1% formic acid in water and 0.001% trifluoroacetic acid in acetonitrile. Detection for both conventional and high-speed LC/MS/MS methods was by positive ion electrospray tandem mass spectrometry on a ThermoElectron Finnigan TSQ Quantum Ultra, where enhanced resolution (RP 2000; 0.2,amu) was used for high-speed LC/MS/MS. The standard curve, ranging from 0.5 to 100,ng/mL, was fitted to a 1/x weighted quadratic regression model. This combined PPT/SPE procedure effectively eliminated time-consuming sorbent conditioning and wash steps, which are essential for a conventional mixed-mode SPE procedure, but retained the advantages of both PPT (removal of plasma proteins) and mixed-mode SPE (analyte selectivity). The validation results demonstrated that this PPT/SPE procedure was well suited for both conventional and high-speed LC/MS/MS analyses. In comparison with a conventional mixed-mode SPE procedure, the simplified PPT/SPE process provided comparable sample extract purity. This simple sample clean-up procedure can be applied to other basic compounds with minor modifications of PPT solvents. Copyright © 2006 John Wiley & Sons, Ltd. [source] Sensitivity improvement of circular dichroism detection in HPLC by using a low-pass electronic noise filter: Application to the enantiomeric determination purity of a basic drugCHIRALITY, Issue 2 2007Marie Lorin Abstract The quality control of chiral drugs requires the determination of their enantiomeric purity. Nowadays, circular dichroism (CD) spectroscopy is gaining increasing importance in pharmaceutical analysis because of the commercially available CD detector in liquid chromatography. The separation of the two enantiomers of a basic drug (efaroxan) was achieved by high performance liquid chromatography using an amylose-derivated column with both UV and CD detections. A baseline-resolved separation (resolution: 5) was obtained after optimization of the mobile phase composition with hexane-ethanol-diethylamine (90:10:0.05; v/v/v). The use of a commercial low-pass electronic noise filter of the CD signal has improved the signal-to-noise ratio by a factor twelve and allowed the quantitation of each enantiomer in the 1.25,300 ,g ml,1 concentration range. The CD linear calibration curve, expressed in terms of stereoisomer height ratio versus concentration ratio, was plotted over the 0.4,6% range. A correlation coefficient greater than 0.999 was obtained by least-squares regression and the limit of detection for the distomer/eutomer ratio was estimated at 0.14%. Although the method validation showed good repeatability on the retention times (RSD < 0.9%), on the peak height ratios (RSD < 8.7%) of each enantiomer only up to 99.2% enantiomeric purity was achieved. Chirality, 2006. © 2006 Wiley-Liss, Inc. [source] Glycogen: A novel branched polysaccharide chiral selector in CEELECTROPHORESIS, Issue 6 2010Jiaquan Chen Abstract Various chiral selectors have been employed in CE and among them linear polysaccharides exhibited powerful enantioselective properties. Different from linear polysaccharides, the use of branched polysaccharides as chiral selectors in CE has not been reported previously. In this study glycogen belonging to the class of branched polysaccharides was used as a novel chiral selector for the enantiomeric separations for the first time. Since glycogen is electrically neutral, the method is applicable to ionic compounds. Eighteen chiral compounds including 12 basic drugs and six acidic drugs have been tested to demonstrate the potential of this chiral selector. BGE and selector concentrations and buffer pH were systematically optimized in order to obtain successful chiral separations. Among the tested compounds, the enantiomers of ibuprofen, which is an acidic drug, were successfully recognized by 3.0%,w/v glycogen with 90,mM Tris-H3PO4 buffer (pH 7.0). The enantiomers of basic drugs such as citalopram, cetirizine and nefopam were also baseline-resolved with 50,mM Tris-H3PO4 buffer (pH 3.0) containing 3.0% glycogen. Amlodipine belonging to basic compound only gave partial enantioseparation under the above-mentioned condition. [source] Cyclodextrin-based nonaqueous electrokinetic chromatography with UV and mass spectrometric detection: Application to the impurity profiling of amiodarone,ELECTROPHORESIS, Issue 17 2008Roelof Mol Abstract The potential of nonaqueous electrokinetic chromatography (NAEKC) using cyclodextrins (CD) for the analysis of basic drugs and related compounds was evaluated. Both UV absorbance and mass spectrometric (MS) detection were employed. Addition of neutral CD to the NA background electrolyte did not significantly enhance the separation of a test mixture of basic drugs, and no change in selectivity was observed. In contrast, anionic single-isomer-sulfated CD strongly added to the selectivity of the NAEKC system inducing an improved resolution among the test compounds and increasing the migration time window. The applicability of the NAEKC system using anionic CD is demonstrated by the profiling of a sample of the drug amiodarone that had been stored for 1,year at room temperature. Amiodarone is poorly soluble in water. NAEKC-UV analysis indicated the presence of at least seven impurities in the amiodarone sample. In order to identify these compounds, the NAEKC system was coupled directly to electrospray ionization (ESI) ion-trap MS. The total of detected impurities increased to 12 due to the added sensitivity and selectivity of MS detection. Based on the acquired MS/MS data, three sample constituents could be identified as ,known' impurities (British Pharmacopoeia), whereas for three unknown impurities molecular structures could be proposed. Estimated limits of detection for amiodarone using the NAEKC method were 1,,g/mL with UV detection and 15,ng/mL with ESI-MS detection (full-scan). Based on relative responses, the impurity content of the stored drug substance was estimated to be 0.33 and 0.47% using NAEKC-UV and NAEKC-ESI-MS, respectively. [source] Simultaneous enantioseparation and sensitivity enhancement of basic drugs using large-volume sample stackingELECTROPHORESIS, Issue 19 2007Nerissa L. Deńola Abstract Simultaneous enantioseparation with sensitive detection of four basic drugs, namely methoxamine, metaproterenol, terbutaline and carvedilol, using a 20-,m ID capillary with native ,-CD as the chiral selector was demonstrated by the large-volume sample stacking method. The procedure included conventional sample loading either hydrodynamically or electrokinetically at longer injection times without polarity switching and EOF manipulation. In comparison to conventional injections, depending on the analyte, about several hundred- and a thousand-fold sensitivity enhancement was achieved with the hydrodynamic and the electrokinetic injections, respectively. The simple method developed was applied to the analysis of racemic analytes in serum samples and better recovery was achieved using hydrodynamic injection than electrokinetic injection. [source] Characterization of basic drug,human serum protein interactions by capillary electrophoresisELECTROPHORESIS, Issue 17 2006María A. Martínez-Gómez Abstract Drug,protein interactions are determining factors in the therapeutic, pharmacodynamic and toxicological drug properties. The affinity of drugs towards plasmatic proteins is apparently well established in bibliography. Albumin (HSA) especially binds neutral and negatively charged compounds; ,1 -acid glycoprotein,(AGP) binds many cationic drugs, lipoproteins bind to nonionic and lipophilic drugs and some anionic drugs while globulins interact inappreciably with the majority of drugs. In this paper, the characterization of the interaction between cationic drugs, ,-blockers and phenotiazines towards HSA, AGP, and both HSA + AGP mixtures of proteins under physiological conditions by CE-frontal analysis is presented. Furthermore, the binding of these drugs to all plasmatic proteins is evaluated by using ultrafiltration and CE. The results indicate that the hydrophobic character of compounds seems to be the key factor on the interaction between cationic drugs towards proteins. In fact, hydrophobic basic drugs bind in great extension to HSA, while hydrophilic basic drugs present low interactions with proteins and bind especially to AGP. [source] Optimization of capillary electrophoretic enantioseparation for basic drugs with native ,-CD as a chiral selectorELECTROPHORESIS, Issue 12 2006Nerissa L. Deńola Abstract This study presents the advantages of the 20,µm inner diameter (id) capillary for the enantioseparation of ten basic drugs with native ,-CD as the chiral selector. The apparent binding constants of each enantiomeric pair were determined to calculate the optimum ,-CD concentration ([,-CD]opt) and the optimization was subsequently carried out. Comparison of the 20,µm id with 50,µm id were made in terms of the results obtained in the optimization and detection limits. Applying the optimum conditions for each compound, reproducible results (RSD from 0,3; n>5) were obtained for the 20,µm id capillary. Although the sensitivity is lower in the 20,µm id capillary, the LOD determined using this capillary is still found to be acceptable for the ten basic drugs studied. Enhanced resolution and faster analysis times were the main advantages observed with the use of this capillary in enantioseparation. [source] Influence of methanol on the enantioresolution of antihistamines with carboxymethyl-,-cyclodextrin in capillary electrophoresisELECTROPHORESIS, Issue 16 2004Ann Van Eeckhaut Abstract According to the model of Wren and Rowe, the separation between two enantiomers in capillary electrophoresis (CE) decreases if an organic modifier is added to the run buffer containing a neutral cyclodextrin (CD) in a concentration below its optimal value in a solvent-free system. In previous work, however, it was observed that the addition of methanol to the background electrolyte (BGE) containing not charged carboxymethyl-,-CD in a concentration below its optimal value, increased the enantioresolution of dimetindene maleate. The enantioresolution decreased when other organic modifiers (ethanol, isopropanol or acetonitrile) were added and/or when other neutral (,-CD, hydroxypropyl-,-CD) or chargeable (carboxyethyl-,- and succinyl-,-CD) CDs were used. In this CE study further attempts are made to elucidate the observed phenomena through investigating other basic drugs. The effect of organic modifier and CD concentration on the enantioseparation was studied by means of central composite designs. It is shown that obtaining this increase in enantioresolution depends upon the type of CD, the type of organic modifier, and the structure of the analytes. It was also observed that small differences in the structure of the analytes or the CD could have an influence on the enantioresolution. The addition of methanol also resulted in different effects on the resolution of closely related analytes. [source] Ion-exchange resins as drug delivery carriersJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2009Xiaodi Guo Abstract There are many reports in the literature referring to the utilization of drug bound to ion-exchange resin (drug,resinate), especially in the drug delivery area. Ion-exchange resin complexes, which can be prepared from both acidic and basic drugs, have been widely studied and marketed. Salts of cationic and anionic exchange resins are insoluble complexes in which drug release results from exchange of bound drug ions by ions normally present in body fluids. Resins used are polymers that contain appropriately substituted acidic groups, such as carboxylic and sulfonic for cation exchangers; or basic groups, such as quaternary ammonium group for anion exchangers. Variables relating to the resin are the exchange capacity; degree of cross-linking, which determines the permeability of the resin, its swelling potential, and the access of the exchange sites to the drug ion; the effective pKa of the exchanging group, which determines the exchange affinity; and the resin particle size, which controls accessibility to the exchange ions. In this review, the properties of ion-exchange resins, selection of drugs that lend themselves to such an approach, selection of the appropriate resin, preparation of drug,resinate, evaluation of drug release, recent developments of drug,resinates, and applications are discussed. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3886,3902, 2009 [source] Rapid throughput screening of apparent KSP values for weakly basic drugs using 96-well formatJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2008Jeremy Guo Abstract A rapid-throughput screening assay was developed to estimate the salt solubility parameter, KSP, with a minimal quantity of drug. This assay allows for early evaluation of salt limited solubility with a large number of counter-ions and biologically promising drug leads. Drugs dissolved (typically 10 mM) in DMSO are robotically distributed to a 96-well plate. DMSO is evaporated, and drugs are equilibrated with various acids at different concentrations (typically <1 M) to yield final total drug concentrations around 2.5 mM. The plate is checked for precipitation. Filtrates from only those precipitated wells were subjected to rapid gradient HPLC analysis. An iterative procedure is employed to calculate all species concentrations based on mass and charge balance equations. The apparent KSP values assuming 1:1 stoichiometry are determined from counter-ion and ionized drug activities. A correlation coefficient >0.975 for eight drugs totaling 16 salts is reported. Intra-day and inter-day reproducibility was <10%. Conventional apparent KSP measurements were translated to 96-well format for increased throughput and minimal drug consumption (typically 10 mg) to evaluate at least eight different counter-ions. Although the current protocol estimates KSP from 10,3 to 10,7 M, the dynamic range of the assay could be expanded by adjusting drug and counter-ion concentrations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2079,2090, 2008 [source] Microenvironmental pH modulation in solid dosage formsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2007Sherif I. Farag Badawy Abstract There are many reports in the literature referring to the effect of ,microenvironmental pH' on solid dosage form performance, particularly stability and dissolution profiles. Several techniques have been proposed for the measurement of the microenvironmental pH. Those techniques use certain assumptions and approximations and many of them employ a solution calibration curve of a probe to predict hydrogen ion activity in a substantially dry solid. Despite the limitation of the methodology, it is clear from the literature that microenvironmental pH has a significant impact on stability of compounds which demonstrate pH dependent stability in solution. Degradation kinetics of such compounds, and in some cases degradation profile as well, are dependent on the microenvironmental pH of the solid. Modulation of the microenvironmental pH through the use of pH modifiers can hence prove to be a very effective tool in maximizing solid dosage form stability. Judicial selection of the appropriate pH modifier, its concentration and the manufacturing process used to incorporate the pH modifier is necessary to enhance stability. Control of microenvironmental pH to maximize stability can be achieved without the use of pH modifier in some cases if an appropriate counter ion is used to provide an inherently optimal pH for the salt. Microenvironmental pH modulation was also shown to control the dissolution profile of both immediate and controlled release dosage forms of compounds with pH dependent solubility. The pH modifiers have been used in conjunction with high energy or salt forms in immediate release formulations to minimize the precipitation of the less soluble free form during initial dissolution. Additionally, pH modifiers were utilized in controlled release dosage forms of weakly basic drugs which exhibit diminished release in dissolution media with high pH. The incorporation of acidic pH modifiers in the controlled release formulation increases the solubility of the basic drug even as the high pH dissolution medium enters into the dosage form hence increasing drug release rate. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 948,959, 2007 [source] Self-assembly of drug,polymer complexes: A spontaneous nanoencapsulation process monitored by atomic force microscopy,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2003Mireia Oliva Abstract Since hydrophilic matrices were proposed for controlled drug delivery, many polymeric excipients have been studied to make drug release fit the desired profiles. It has been pointed out that ,-carrageenan, a sulfated polymer from algae, can suitably control the release rate of basic drugs from hydrophilic matrices. Furthermore, the relevance of hydrophobic interactions in drug,polymer aqueous systems has already been demonstrated, although no references to morphological features as well as to the kinetics of the interaction complexes formation have been published to date. In this work, we propose a method to monitor the topographical evolution of the interaction between ,-carrageenan and dexchlorpheniramine maleate, in order to determine how the release profiles can be so easily controlled. For this purpose, solutions of both polymer and drug were prepared at very low concentration. Solutions were mixed and small volumes were taken every hour for over a period of 24 h and subsequently analyzed. The characterization technique used, atomic force microscopy, provides a high resolution, allowing plotting of three-dimensional images of the sample morphology within the nanometric scale. The results demonstrate that ,-carrageenan is able to nanoencapsulate spontaneously dexchlorpheniramine maleate molecules, which offers the possibility of controlling the release rate of the drug with no need of complex technological processes. Moreover, this work demonstrates the suitability of atomic force microscopy for the specific case of the on-time monitoring of interaction processes that occur in pharmaceutical systems. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:77,83, 2003 [source] Preparation, characterization and taste-masking properties of polyvinylacetal diethylaminoacetate microspheres containing trimebutineJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2002Yoshimi Hashimoto The objectives of this study were to produce acid soluble, polyvinylacetal diethylaminoacetate (AEA) microspheres containing trimebutine (as maleate), using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method, to characterize their in-vitro release properties, and to evaluate the taste-masking potential of this formulation in human volunteers. The pH of the external aqueous phase was the critical factor in achieving a high loading efficiency for trimebutine in the microencapsulation process; nearly 90% (w/w) loading efficiency was obtained at above pH 10. Trimebutine was completely released from AEA microspheres within 10 min in a dissolution test at pH 1.2, simulating conditions in the stomach, whereas at pH 6.8, the pH in the mouth, only small quantities of trimebutine were released in the initial 1,2 min. The results of a gustatory sensation test in healthy volunteers confirmed the taste-masking effects of the AEA microspheres. Finally, an attempt was made to encapsulate the salts of other basic drugs (lidocaine, imipramine, desipramine, amitriptyline, promethazine and chlorpheniramine) into AEA microspheres using the w/o/w emulsion evaporation method. The loading efficiencies were ranked in almost inverse proportion with the solubility of the drugs in the external aqueous phase. This study demonstrated the possibility of masking the taste of salts of basic drugs by microencapsulation with AEA using a w/o/w emulsion solvent evaporation method. [source] Supported liquid membranes in hollow fiber liquid-phase microextraction (LPME) , Practical considerations in the three-phase modeJOURNAL OF SEPARATION SCIENCE, JSS, Issue 9 2007Kari Folde Bĺrdstu Abstract In this work, three-phase liquid-phase microextraction (LPME) based on a supported liquid membrane (SLM) sustained in the wall of a hollow fiber was investigated with special focus on optimization of the experimental procedures in terms of recovery and repeatability. Recovery data for doxepin, amitriptyline, clomipramine, and mianserin were in the range of 67.8,79.8%. Within-day repeatability data for the four basic drugs were in the range of 4.1,7.7%. No single factor was found to be responsible for these variations, and the variability was caused by several factors related to the LPME extractions as well as to the final HPLC determination. Although the volume of the SLM varied within 0.4,3.1% RSD depending on the preparation procedure, and the volume of the acceptor solution varied within 4.8% RSD, both recoveries and repeatability were found to be relative insensitive to these variations. Thus, the handling of microliters of liquid in LPME was not a very critical factor, and the preparation of the SLM was accomplished in several different ways with comparable performance. Reuse of hollow fibers was found to suffer from matrix effects due to built-up of analytes in the SLM, whereas washing of the hollow fibers in acetone was beneficial in terms of recovery, especially for the extraction of the most hydrophobic substances. Several of the organic solvents used in the literature as SLM suffered from poor long-term stability, but silicone oil AR 20 (polyphenyl-methylsiloxane), 2-nitrophenyl octyl ether (NPOE), and dodecyl acetate (DDA) all extracted with unaltered performance even after 60 days of storage at room temperature. [source] Evaluation of the silanol-suppressing potency of ionic liquidsJOURNAL OF SEPARATION SCIENCE, JSS, Issue 8 2006Micha, Piotr Marsza Abstract Recently, increasing attention has been paid to the use of ionic liquids for high-performance liquid chromatography (HPLC) and capillary electrophoresis. In the present study, the silanol-suppressing potency of ionic liquids was evaluated by HPLC using the two-retention site model proposed previously by Nahum and Horváth (J. Chromatogr. 1981, 203, 53,63). The binding constant, KA, in that approach has been demonstrated to reliably reflect the ability of the ionic liquids to block the silanols of the silica support material of the stationary phase. The determinations were carried out for ionic liquids of the 1-alkyl-3-methylimidazolium group with the use of a series of basic drugs as the test analytes. Comparison of ionic liquids with standard mobile phase additives such as triethylamine showed the former to possess advantages as silanol suppressors in HPLC. The main advantage of the method is that it provides a simple and fast determination of the silanol complex stability, which allowed comparison of the suppressing efficiency of several ionic liquids. [source] HPLC of basic drugs using non-aqueous ionic eluents: evaluation of a 3,,m strong cation-exchange materialBIOMEDICAL CHROMATOGRAPHY, Issue 3 2010Phillip E. Morgan Abstract HPLC columns packed with 3,,m particle size HPLC Technology Techsphere SCX (propylsulfonic acid-modified) silica offer considerable advantages over 5,,m SCX packings in the analysis of basic drugs using 100% methanol eluents containing an ionic modifier such as ammonium perchlorate. The basic drugs studied included clozapine and norclozapine, olanzapine, quinine and quinidine, and amitriptyline, nortriptyline, imipramine and desipramine. The 3,,m column was not only more efficient for a given column length compared with 5,,m materials, but also elution times were less, a phenomenon observed in reversed-phase systems. The high efficiencies and excellent peak shapes obtained with the 3,,m SCX-modified packing together with the relatively low back-pressures attained show that such materials deserve serious consideration by laboratories involved in the analysis of basic drugs. Manufacturers should offer such packings as a matter of routine. Alternative ionic modifiers such as ammonium acetate are available for use with mass spectrometric detection if required. Copyright © 2009 John Wiley & Sons, Ltd. [source] Comparison between micellar liquid chromatography and capillary zone electrophoresis for the determination of hydrophobic basic drugs in pharmaceutical preparationsBIOMEDICAL CHROMATOGRAPHY, Issue 1 2007S. Torres-Cartas Abstract The determination of highly hydrophobic basic compounds by means of conventional reversed-phase liquid chromatographic methods has several drawbacks. Owing to the characteristics of micellar liquid chromatography (MLC) and capillary electrophoresis (CE), these techniques could be advantageous alternatives to reversed-phase chromatographic methods for the determination of these kinds of compounds. The objective of this study was to develop and compare MLC and CE methods for the determination of antipsychotic basic drugs (amitryptiline, haloperidol, perphenazine and thioridazine) in pharmaceutical preparations. The chromatographic determination of the analytes was performed on a Kromasil C18 analytical column; the mobile phase was 0.04 m cetyltrimethylammonium bromide (CTAB), at pH 3, containing 5% 1-butanol, at a flow rate of 1 mL/min. The CE separation was performed in a fused-silica capillary with a 50 mm tris-(hydroxymethyl)-aminomethane buffer, pH 7, at an applied voltage of 20 kV, using barbital as internal stardard. The proposed methods are suitable for a reliable quantitation of these compounds in the commercial tablets and drops in terms of accuracy and precision and require a very simple pre-treatment of the samples. By comparing the performance characteristics and experimental details of the MLC and CE methods we conclude that CE seems to be slightly better than MLC in the determination of highly hydrophobic compounds in pharmaceuticals in terms of resolution and economy, taking into account that the limits of detection are not a handicap in pharmaceutical samples. Copyright © 2006 John Wiley & Sons, Ltd. [source] Separation of Basic Drugs Using Pressurized Capillary ElectrochromatographyCHINESE JOURNAL OF CHEMISTRY, Issue 4 2003Zhang Kai Abstract A novel pressurized capillary electrochromatography (PCEC) was developed to separate basic drugs on strong cation exchange (SCX) column. The separation result by using PCEC was better than that by using micro-HPLC. The effects of electrical field and pressure on plate height and resolution were investigated. Influence of organic modifier, ionic strength and pH value of buffer on retention behavior were evaluated, and the separation mechanism was also discussed. [source] | |||||||||||||