RESUMO
The crystallization of active pharmaceutical ingredients (APIs) in matrix-type transdermal patches has implications for the rate of drug absorption through the skin and patch adhesion strength. Therefore, the presence or absence and the degree of API crystallinity must be controlled to guarantee the quality of patches. In this study, the utility of laboratory-level X-ray diffractometers for the detection and analysis of crystalline APIs in transdermal patches was investigated using medical patches of tulobuterol and isosorbide dinitrate. Several matrix-type patches employ a controlled drug delivery system containing intentionally crystallized API. Both benchtop and high-resolution laboratory X-ray diffractometers can detect several characteristic peaks of the APIs in these patches even if the patches are wrapped in an outer bag, although a benchtop model provides peak heights one-seventh to one-fifth that of a high-resolution instrument. An isosorbide dinitrate patch containing an unintentionally crystallized spot was wrapped in an outer bag, followed by measurements using both X-ray diffractometers. For both instruments, several isosorbide dinitrate-derived peaks were detected only at the crystallized spot, although the signal-to-noise ratio was poorer for the benchtop model. These results show that a high-resolution X-ray diffractometer is advantageous for high-detection sensitivity and offers a high degree of freedom of the measurement position on the sample. It was concluded that a laboratory-level high-resolution X-ray diffractometer can be used to examine the crystalline state of APIs in patches inside an unopened outer bag.
Assuntos
Dinitrato de Isossorbida/análise , Terbutalina/análogos & derivados , Adesivo Transdérmico , Difração de Raios X/métodos , Adesividade , Cristalização , Dinitrato de Isossorbida/química , Pele/metabolismo , Absorção Cutânea , Terbutalina/análise , Terbutalina/químicaRESUMO
The chiral separation ability of the full library of methylated-ß-cyclodextrins towards pharmacologically significant racemic drugs including basic compounds was studied by chiral CE. The syntheses of all the methylated, single isomer ß-cyclodextrins were revised and optimized and the aqueous solubility of the derivatives was unambiguously established. The three most relevant commercially available methylated isomeric mixtures were also included in the screening, so a total of ten various methylated CDs were investigated. The effects of the selector concentration on the enantiorecognition properties at acidic pH were investigated. Among the dimethylated ß-cyclodextrins, the heptakis (2,6-di-O-methyl)-ß-cyclodextrin isomer (2,6-DIMEB) resulted to be the most versatile chiral selector. Terbutaline was selected as a model compound for the in-depth investigation of host-guest enantiodiscrimination ability. The association constants between the two terbutaline enantiomers and 2,6-DIMEB were determined in order to support that the enantioseparation is driven by differences is host-guest binding. The migration order of the enantiomers was confirmed by performing spiking experiments with the pure enantiomers. 1D and 2D NMR spectroscopy was applied to the 2,3-, and 2,6-DIMEB/terbutaline systems to rationalize at molecular level the different enantioseparation ability of the dimethylated ß-cyclodextrin selectors.
Assuntos
Eletroforese Capilar/métodos , beta-Ciclodextrinas/química , Modelos Químicos , Modelos Moleculares , Estereoisomerismo , Terbutalina/análise , Terbutalina/química , Terbutalina/isolamento & purificaçãoRESUMO
Nowadays, development of highly efficient potentiometric sensors attracts the attention of many researchers over the world; due to the great expansion of portable analytical devices. This study aims to apply a current development to the construction and sense of carbon paste sensors based on flowered-like Mg-Al layered double hydroxides/multiwalled carbon nanotubes (FLLDH/MWCNTs) (sensor Ð), FLLDH/titanate nanotubes (TNTs) (sensor ÐÐ) and MWCNTs/TNTs (sensor ÐÐÐ) nanocomposites for bambuterol hydrochloride analysis; to enhance the potentiometric response towards determination of the drug. The sensors exhibited excellent Nernstian slopes 58.8⯱â¯0.5, 58.5⯱â¯0.8 and 57.4⯱â¯0.7â¯mV/decade with linear working ranges of 1.0â¯×â¯10-7-1.0â¯×â¯10-2, 1.0â¯×â¯10-6-1.0â¯×â¯10-2 and 1.0â¯×â¯10-7-1.0â¯×â¯10-2â¯molâ¯L-1, detection limits 2.3â¯×â¯10-8, 2.5â¯×â¯10-7and 7.5â¯×â¯10-8â¯molâ¯L-1 and quantification limits of 7.6â¯×â¯10-8, 8.3â¯×â¯10-7and 2.5â¯×â¯10-7â¯molâ¯L-1 for sensor Ð, ÐÐ and ÐÐÐ, respectively. The selectivity behaviour of the investigated sensors was tested against biologically important blood electrolytes (Na+, K+, Mg2+, Ca2+). The proposed analytical method was successfully applied for BAM determination in pure drug, pharmaceutical products, surface water, human plasma and urine samples with excellent recovery data (99.62, 99.10 and 98.95%) for the three sensors, respectively.
Assuntos
Nanocompostos/química , Nanotubos de Carbono/química , Potenciometria , Terbutalina/análogos & derivados , Alumínio/química , Água Doce/química , Humanos , Concentração de Íons de Hidrogênio , Hidróxidos/química , Limite de Detecção , Magnésio/química , Terbutalina/análise , Terbutalina/sangue , Terbutalina/urinaRESUMO
OBJECTIVE: The objective of the present work was to develop and validate a simple, sensitive, rapid and stable reverse-phase high performance liquid chromatography (RP-HPLC) method for a combination of Terbutaline sulphate (TSL), Ambroxol hydrochloride (AML) and Guaifenesin (GFN). METHOD: The combination of these drugs was analyzed by using Shimadzu LC 2010 CHT high performance liquid chromatography (HPLC). Successful separation was achieved by isocratic elution on a reverse-phase C18 column (sun fire) (250mm, 4.6mm, 5µ), using a mobile phase consisting of buffer: acetonitrile in the ratio 80: 20 (buffer - 0.1% v/v triethyleamine pH-3.0) followed by 1.0mL/min flow rate. The wavelength of detection was at 220nm. RESULT: The chromatographic retention times were consistent at 3.0, 10.5 and 13.8minutes for TSL, AML and GFN respectively. For these three compounds, the lower limit of detection was 1.0, 1.25, and 1.5µg/mL and lower limit of quantification was 3.3, 4.1 and 5.0µg/mL respectively. The linearity concentrations established for TSL, AML and GFN were 1.0-7.0, 1.5-7.5 and 4.0-14.0µg/mL respectively. The correlation coefficients for all the drugs were found to be greater than 0.999. The relative standard deviation of inter- and intra-day were less than 2.0%. CONCLUSION: This method provides a necessary tool for quantification of the selected drugs for their assay. The proposed method is simple, accurate, reproducible and applied successfully to analyze three compounds in pure as well dosage form.
Assuntos
Ambroxol/análise , Broncodilatadores/análise , Expectorantes/análise , Guaifenesina/análise , Terbutalina/análise , Cromatografia de Fase Reversa , Formas de Dosagem , Combinação de Medicamentos , Limite de Detecção , Reprodutibilidade dos Testes , Espectrofotometria UltravioletaRESUMO
Exploration of the simple and stable coating methods is of great significance in capillary electrochromatography (CEC). In this work, a lysozyme assemble supramolecular membrane coated capillary column was developed for CEC chiral separation. Taking advantage of phase transformation of lysozyme, the coating process was achieved within 1.0â¯h thus to a large extent reduced the capillary preparation time and simplified the coating procedure. The successful fabrication of the supramolecular membrane coated capillary was verified by scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), fluorescence imaging, and electroosmotic flow (EOF). The separation capacity of the coated capillary was evaluated by analysis of different chiral analytes, including chiral amine drug and neurotransmitters, and good enantioseparation efficiency was achieved for the three pairs of enantiomers. For three consecutive runs, the relative standard deviations (RSD) for the migration time of the analytes for intra-day (nâ¯=â¯3), inter-day (nâ¯=â¯3) and column-to-column (nâ¯=â¯3) were in the range of 0.7-1.5%, 2.7-3.6%, and 4.5-5.8%, respectively. Additionally, the supramolecular membrane coated capillary column could run consecutively 100 times without observable change in the separation efficiency, proving the feasibility of the coating method based on the adhesion of the protein-based supramolecular membrane.
Assuntos
Eletrocromatografia Capilar/métodos , Membranas Artificiais , Muramidase/química , Epinefrina/análise , Epinefrina/química , Isoproterenol/análise , Isoproterenol/química , Microscopia Eletrônica de Varredura , Imagem Óptica , Espectroscopia de Infravermelho com Transformada de Fourier , Terbutalina/análise , Terbutalina/químicaRESUMO
BACKGROUND AND OBJECTIVE: Terbutaline is a ß-agonist that used as growth promoters to improved carcass chemical composition of chicks without residues. The purpose of the present investigation is exploring the effect of different dietary levels and duration of terbutaline on the productive performance, biochemical and carcass quality traits including residue of acres broiler. MATERIALS AND METHODS: A total of 150 one-day-old arbor acres broiler chicks were allotted into 5 groups (3 replicates per each). Group 1 was fed on the basal diet without supplement, while groups 2-5 fed on the basal diet supplemented by 5 or 10 mg terbutaline kg-1 diet during 1-42 or 21-42 days, respectively. RESULTS: When handling the dietary levels and duration of terbutaline, results of the present study showed that10 mg terbutaline kg-1 diet during the whole experimental period is a more effective dose for improvement of growth performance with significant (p<0.05) increased serum protein and breast muscles relative weight compared with control. Also, 10 mg terbutaline kg-1 diet during the whole experimental period significantly (p<0.05) increase d CP% (crude protein%) and CHO% (carbohydrate%) of breast muscle and significantly (p<0.05) decreased fat% (ether extract%) of breast muscle and abdominal fat relative weight compared with control. Meanwhile, 5 mg terbutaline kg-1 diet during 1-42 or 21-42 days has no significant effect on the above-mentioned parameters. Regarding residue, the terbutaline residue wasn't detected in broiler meat. CONCLUSION: It can conclude that 10 mg terbutaline kg-1 diet during the whole experimental period is a better dose and duration for improving growth performance, the chemical composition of breast muscle and carcass traits of broiler chickens with no terbutaline residue in breast muscle.
Assuntos
Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Terbutalina/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Ração Animal/análise , Criação de Animais Domésticos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Dieta/veterinária , Suplementos Nutricionais , Resíduos de Drogas/análise , Lipídeos/sangue , Carne/análise , Terbutalina/análiseRESUMO
Bambuterol (BAM) and terbultaline (TER) are well known and effective bronchodilators. In this article highly sensitive, green and cost-effective spectrofluorimetric methods are designed to determine low concentrations of such drugs. The proposed methods are based on an investigation of the native fluorescence properties of aqueous solutions of BAM at 298 nm after excitation at 263 nm and of TER at 313 nm after excitation at 275 nm. Under optimum conditions, the plots of the relative fluorescence intensity versus concentration were rectilinear over the range 0.1-1.2 µg/mL for BAM and 0.05-0.5 µg/mL for TER with a limit of quantitation of 0.067 µg/mL for BAM and 0.018 µg/mL for TER. The methods are simple and hence suitable for application to the quantification of BAM and TER in syrups and tablets without interference from common excipients. Furthermore, based on United States Pharmacopeia (USP) guidelines, the application was extended to determine the content uniformity of the cited drugs in low dose tablets. The developed methods were fully validated according to the guidelines of the International Conference on Harmonization (ICH).
Assuntos
Espectrometria de Fluorescência/métodos , Terbutalina/análogos & derivados , Terbutalina/análise , Calibragem , Química Verde , Concentração de Íons de Hidrogênio , Limite de Detecção , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Solventes/química , Comprimidos/análiseRESUMO
An analytical method was developed to simultaneously determine the residues of four ß2-agonists in animal foods by high performance liquid chromatography/electrospray-tandem mass spectrometry (HPLC-MS/MS). Samples were extracted with 5% (mass fraction) trichloracetic acid, and then cleaned up by two solid phase extraction cartridges (HLB and ProElut PXC). Quantification of the four ß2-agonists was achieved by HPLC-MS/MS in multiple reaction monitoring (MRM) using internal standard method. The limits of detection (S/N=3) of clenbuterol, salbutamol, ractopamine and terbutaline were 0. 05, 0. 05, 0. 05 and 0. 2 µg/kg, and the limits of quantification (S/N= 10) were 0. 25, 0. 25, 0. 1 and 0. 5 µg/kg, respectively. The average recoveries of the four ß2-agonists spiked in blank samples at the spiked levels of 2. 5, 5 and 10 µg/kg were 90. 3%-120. 5% with the relative standard deviation (RSD) range of 1. 60%-9. 33%. The method is reliable, sensitive, good recovery and repeatability. It is suitable for the determination of the residues of the four ß2-agonists in animal foods.
Assuntos
Agonistas Adrenérgicos beta/análise , Ração Animal/análise , Cromatografia Líquida de Alta Pressão , Resíduos de Drogas/análise , Espectrometria de Massas em Tandem , Albuterol/análise , Clembuterol/análise , Fenetilaminas/análise , Extração em Fase Sólida , Terbutalina/análiseRESUMO
In this study, homemade disposable gold electrodes made from recordable compact disks were modified with carbon nanotubes for amperometric quantification of terbutaline sulfate in pharmaceutical products. A flow cell using an impingent jet of solution on the electrode surface was build and used for amperometric detection, and a series of experiments were carried out to find the best experimental conditions for the new electrode in a specially designed cell. A linear response for terbutaline was obtained in the range from 3.0 × 10(-6) to 5.0 × 10(-4) mol L(-1) (at 0.63 V vs. Ag/AgCl). The limits of detection and quantification were calculated as 5.8 × 10(-7) mol L(-1) (S/N = 3) and 1.9 × 10(-6) mol L(-1) (S/N = 10), respectively. A frequency of 30 injections h(-1) was attained. The proposed method was successfully applied to the analyses of commercial syrup samples, and all results were in good agreement with those obtained by using high performance liquid chromatography and capillary electrophoresis-tandem mass spectrometry.
Assuntos
Discos Compactos , Eletroquímica/instrumentação , Limite de Detecção , Nanotubos de Carbono/química , Preparações Farmacêuticas/química , Terbutalina/análise , Eletrodos , Ouro/química , Terbutalina/química , Fatores de TempoRESUMO
An accurate and precise determination of terbutaline has been carried out using a glassy carbon electrode (GCE) modified with a composite of multi-walled carbon nanotubes (MWCNTs) and nanoparticles of zirconium oxide (ZrO2NPs). Energy dispersive X-ray and scanning electron microscopic techniques were utilized for the characterization of the composite layer. Terbutaline exhibited a broad oxidation peak at 770mV on a GCE. However, MWCNTs/GCE presented an electrocatalytic effect toward the oxidation of terbutaline with a better anodic peak at 660mV. Furthermore, the electrochemical behavior of terbutaline has greatly been improved at a GCE modified with a composite of MWCNTs and nanoparticles of ZrO2. The ZrO2NPs/MWCNTs/GCE exhibited a sharp anodic wave at 645mV with a large enhancement of the current response for terbutaline. Square wave voltammetry (SWV) was performed for the determination of terbutaline at ZrO2NPs/MWCNTs/GCE. A linear plot was obtained for the current responses of terbutaline against concentrations in the range of 10-160nM yielding a detection limit of 2.25nM (based on 3Sb/m). Improved voltammetric behavior, long-time stability and good reproducibility were obtained for terbutaline at the proposed electrode. A mean recovery of 101.2% with an RSD% of 1.9 was obtained for the analysis of the drug formulation. The accurate and precise quantification of terbutaline makes the ZrO2NPs/MWCNTs/GCE system of great interest for monitoring its therapeutic use.
Assuntos
Nanopartículas/química , Terbutalina/análise , Zircônio/química , Eletrodos , Humanos , Nanopartículas/ultraestrutura , Urina/químicaRESUMO
High-performance liquid chromatography method for anti-asthmatic ß2-agonist drug bambuterol, its process-related impurities and its major degradation products was developed and validated using quality by design concept. A 3(3) full factorial design was employed to study the effect of three independent factors, namely, ratio of organic modifiers in mobile phase, pH of the buffer and flow rate of the mobile phase. The responses considered were retention time of the last peak and resolution of poorly separated peaks (drug and PR-4 and drug and DP-3). The optimum conditions for separation were determined with the aid of design of experiments. The optimized ternary solvent composition was a mixture of 10 mM ammonium acetate buffer (pH 6.0), methanol and acetonitrile in the ratio of 90:5: 5 (v/v/v) in solvent reservoir A and 10:45:45 (v/v/v) in solvent reservoir B. The separation of the analytes was achieved by using a gradient method. The predictability criteria of the optimized method demonstrated good correlation between observed and predicted response. The method was validated for specificity, linearity, accuracy, precision and robustness in compliance with the International Conference on Harmonization guidelines Q2R1.
Assuntos
Antiasmáticos/análise , Cromatografia Líquida de Alta Pressão/métodos , Terbutalina/análogos & derivados , Cromatografia Líquida de Alta Pressão/instrumentação , Solventes/análise , Terbutalina/análiseRESUMO
A simple, specific, accurate and precise spectrophotometric stability indicating method is developed for determination of bambuterol hydrochloride (BH) in the presence of its degradation product terbutaline (TERB) and in pharmaceutical formulations. A newly developed spectrophotometric method called ratio difference method by measuring the difference in amplitudes between 245 and 260 on of ratio spectra. The calibration curves are linear over the concentration range of 0. 1 - 1 mg . mL-1 for BH and 0. 1-0. 7 mg . mL-1 for TERB with mean percentage recovery of 100. 56 ± 0. 751 and 99. 88 ± 1. 183, respectively. The selectivity of the proposed method is checked using laboratory prepared mixtures. The proposed method has been successfully applied to the analysis of BH in pharmaceutical dosage forms without interference from other dosage form additives and the results have been statistically compared with pharmacopeial method.
Assuntos
Espectrofotometria , Terbutalina/análogos & derivados , Terbutalina/análiseRESUMO
ß-Agonists are a group of illegal feed additives. In this paper, it was found that the light emission produced by the oxidation of luminol by potassium ferricyanide was enhanced by the ß-agonists (ractopamine, salbutamol, and terbutaline). Based on chemiluminescence phenomenon, a novel, rapid, and sensitive microflow injection analysis system on a microfluidic glass chip was established for determination of the ß-agonists. The chip was fabricated from two glass plates (64 mm × 32 mm) with microchannels of 200 µm width and 100 µm depth. The detection limits were achieved at 2.0 × 10(-8) mol/L of ractopamine, 1.0 × 10(-8) mol/L of terbutaline and 5.0 × 10(-7) mol/L of salbutamol. In this report, our method was applied for determination of the ß-agonists in swine hair from three different sources with satisfactory results.
Assuntos
Agonistas Adrenérgicos beta/análise , Cabelo/química , Medições Luminescentes/métodos , Agonistas Adrenérgicos beta/química , Albuterol/análise , Animais , Desenho de Equipamento , Ferricianetos/química , Análise de Injeção de Fluxo/instrumentação , Análise de Injeção de Fluxo/métodos , Cinética , Dispositivos Lab-On-A-Chip , Limite de Detecção , Medições Luminescentes/instrumentação , Luminol/química , Fenetilaminas/análise , Sus scrofa , Terbutalina/análiseRESUMO
The enantioseparation of acidic and basic compounds can be successfully achieved in nonaqueous capillary electrophoresis using single-isomer charged ß-cyclodextrin (ß-CD) derivatives of opposite charge to that of the analytes. This chapter describes how to separate the enantiomers of three basic substances selected as model compounds, i.e., alprenolol, bupranolol, and terbutaline, using the negatively charged heptakis(2,3-di-O-acetyl-6-O-sulfo)-ß-CD. The enantiomers of three acidic drugs (tiaprofenic acid, suprofen, and flurbiprofen) are resolved using a monosubstituted amino ß-CD derivative, namely, 6-monodeoxy-6-mono(3-hydroxy)propylamino-ß-CD.
Assuntos
Eletroforese Capilar/métodos , beta-Ciclodextrinas/análise , beta-Ciclodextrinas/química , Alprenolol/análise , Alprenolol/química , Bupranolol/análise , Bupranolol/química , Flurbiprofeno/análise , Flurbiprofeno/química , Propionatos/análise , Propionatos/química , Estereoisomerismo , Suprofeno/análise , Suprofeno/química , Temperatura , Terbutalina/análise , Terbutalina/química , Raios UltravioletaRESUMO
A non-destructive method for analyzing crystalline tulobuterol (TBR; a bronchodilator [ß(2)-blocker]) in transdermal drug delivery system tapes with a crystal reservoir system was developed. A near infrared spectroscopy (NIRS) and a near infrared spectroscopic imaging (NIRI) were used to investigate the distribution of TBR crystals in transdermal tapes. The characteristic peak derived from a first overtone of secondary amine which appears based on crystal growth was used for the detection of crystals. NIR images were composed by the integrated values of that peak at each pixel. The time-course analysis by NIRS showed that the intensity of the peaks gradually increased, and the intensity reached a plateau between day 30 and day 42 after preparation of the model tapes. The authors observed the growth and distribution of TBR crystals in small areas in several types of matrices by NIRI time-course measurement. The authors also found that a macroscopic map can provide a rough distribution map of crystalline TBR in a whole matrix. In the case in which a tape distributed from the innovator was examined, the characteristic peak was also detected through a liner or a supporting board, by transmittance-reflectance NIR measurement.
Assuntos
Espectroscopia de Luz Próxima ao Infravermelho/métodos , Terbutalina/análogos & derivados , Administração Cutânea , Broncodilatadores/análise , Broncodilatadores/química , Cristalização , Terbutalina/análise , Terbutalina/químicaRESUMO
Electromembrane extraction followed by high-performance liquid chromatography coupled with ultraviolet detection was validated for the determination and quantification of salbutamol (SB) and terbutaline in aqueous samples. A 200-V electrical field was applied to extract the analytes from 2.5 mL sample solution with pH 3.0, through an organic phase which consisted of 80% 2-nitrophenyl octyl ether, 10% di-(2-ethylhexyl) phosphate and 10% tris-(2-ethylhexyl)phosphate as supported liquid membrane into an acidic acceptor solution with pH 1.0, located inside the lumen of a hollow fiber. To achieve the best extraction conditions, the organic membrane composition was optimized separately and other parameters, such as extraction time, applied voltage and pH in sample solution and acceptor phase were studied using experimental design. Under optimal conditions, extraction recoveries of 53 and 43% were obtained for SB and terbutaline, respectively, which corresponded to preconcentration factors of 89 for SB and 72 for terbutaline. The method offers acceptable linearity with correlation coefficient higher than 0.9947 and relative standard deviation less than 4.7%. Finally, it was applied for analysis of drugs in wastewater samples.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/análise , Albuterol/análise , Microextração em Fase Líquida , Terbutalina/análise , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/química , Cromatografia Líquida de Alta Pressão , Campos Eletromagnéticos , Membranas ArtificiaisRESUMO
The objective of this study was to develop novel preparation techniques for protein-loaded, controlled release alginate-poloxamer microparticles with a size range suitable for pulmonary administration. Bovine serum albumin (BSA)-loaded microparticles were prepared by spray-drying aqueous polymer-drug solutions, followed by cross-linking the particles in aqueous or ethanolic CaCl(2) or aqueous ZnSO(4) solutions. The microparticles were characterized with respect to their morphology (optical and scanning electron microscopy), particle size (laser light diffraction), calcium content (atom absorption spectroscopy), alginate content (complexation with 1,9-dimethyl methylene blue) and in vitro drug release (modified Franz diffusion cell). The spray-dried microparticles were spherical in shape with a size range of 4-6µm. Aqueous cross-linking led to a significant size increase (10-15µm), whereas ethanolic cross-linking did not. The substantial drug loss (â¼50%) during aqueous CaCl(2) cross-linking could be avoided by using aqueous ZnSO(4) or ethanolic CaCl(2) solutions. Protein release from microparticles cross-linked with ethanolic CaCl(2) solutions was much faster than in the case of aqueous CaCl(2) solutions, probably due to the lower calcium content. The salt concentration and temperature of the cross-linking solutions also affected the composition of and drug release from the microparticles. Cross-linked alginate-poloxamer microparticles can be produced in a size range appropriate for deep lung delivery and with controlled protein release kinetics (time frame: hours to days) with these novel preparation techniques. The systems offer an interesting potential for the controlled mucosal delivery of protein drugs.
Assuntos
Alginatos/química , Cápsulas/química , Composição de Medicamentos/métodos , Soroalbumina Bovina/química , Alginatos/ultraestrutura , Animais , Cloreto de Cálcio/química , Bovinos , Preparações de Ação Retardada/química , Portadores de Fármacos , Humanos , Microscopia Eletrônica de Varredura , Mucosa/metabolismo , Tamanho da Partícula , Soroalbumina Bovina/análise , Solventes/química , Terbutalina/análise , Terbutalina/química , Sulfato de Zinco/químicaRESUMO
A robust and sensitive microemulsion HPLC (MELC) method using oil-in-water microemulsion mobile phase was developed and used for the determination of terbutaline in Bricanyl(®) Turbuhaler. The applicability of microemulsion as an eluent for reversed phase HPLC was examined. In addition, the effect of operating parameters on the separation behaviour was studied. The samples were injected into C18 Spherisorb (250mm×4.6mm×5µm) columns at 25°C using a flow rate of 1ml/min. The mobile phase was 95.5% aqueous orthophosphate buffer (adjusted to pH 3 with orthophosphoric acid), 0.5% ethyl acetate, 1.5% Brij35, and 2.5% 1-butanol, all w/w. The terbutaline peak was detected by fluorescence, using excitation and emission wavelengths of 267 and 313nm, respectively. The accuracy of method was >99% and the calibration curve was linear (r(2)=0.99). The limit of detection (LOD) and limit of quantitation (LOQ) were 8µg/L and 26µg/L, respectively. The intra-day and inter-day precisions (in term of % coefficient of variation) were<1.46% and <0.97%, respectively. The influence of the composition of the microemulsion system was also studied and the method was found to be robust with respect to some changes of the microemulsion components. The microemulsion HPLC method has been applied to determine the content of the emitted dose and the fine particle dose of terbutaline in a Bricanyl(®) Turbuhaler.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Preparações Farmacêuticas/análise , Terbutalina/análise , Soluções Tampão , Emulsões , Concentração de Íons de Hidrogênio , Limite de Detecção , Tamanho da Partícula , Preparações Farmacêuticas/normas , Padrões de Referência , Reprodutibilidade dos Testes , Tensoativos/química , Terbutalina/normasRESUMO
Dry Powder Inhalers have drawn great attention from pharmaceutical scientists in recent years in particular those consisting of low-dose micronized drug particles associated with larger carrier particles and called interactive mixtures. However, there is little understanding of the relation between bulk powder properties such as powder structure and its aerodynamic dispersion performance. The aim of this work was to develop a simple method to measure the air permeability of interactive mixtures used in Dry Powder Inhalers by using Blaine's apparatus--a compendial permeameter and to relate it to the aerodynamic behaviour. The study was done with fluticasone propionate and terbutaline sulphate as drug models that were blended with several lactoses having different particle size distribution thus containing different percentages of fine particle lactose. The quality of the blends was examined by analysing the drug content uniformity. Aerodynamic evaluation of fine particle fraction was obtained using a Twin Stage Impinger. A linear correlation between a bulk property--air permeability of packed powder bed--and the fine particle fraction of drug was observed for the tested drugs. The air permeability reflects the quantity of the free particle fraction in the interparticulate spaces of powder bed that leads to fine particle fraction during fluidization in air flow. A theoretical approach was developed in order to link the air permeability of powder bed and drag force acting on powders during aerosolization process. The permeability technique developed in this study provides a potential tool for screening Dry Powder Inhaler formulations at the development stage.
Assuntos
Androstadienos/farmacocinética , Broncodilatadores/farmacocinética , Sistemas de Liberação de Medicamentos , Inaladores de Pó Seco , Terbutalina/farmacocinética , Administração por Inalação , Ar , Androstadienos/análise , Androstadienos/química , Broncodilatadores/análise , Broncodilatadores/química , Excipientes/química , Fluticasona , Lactose , Modelos Teóricos , Tamanho da Partícula , Permeabilidade , Pós/química , Terbutalina/análise , Terbutalina/químicaRESUMO
Aerosol drugs dominate a significant share of pharmaceutical preparations on the market. A novel sensitive method utilizing nano extractive electrospray ionization mass spectrometry (nanoEESI-MS) has been developed for the rapid analysis of aerosol drug samples with quantitative information. Without any sample pretreatment, aerosol drugs were manually sprayed into the primary ion plume created by a nano electrospray emitter for direct ionization under ambient conditions. The analyte ions of interest were guided into an ion trap mass spectrometer for tandem mass analysis. The active ingredients of various aerosol drugs, such as econazole nitrate, beclomethasone dipropionate, binary mixture of methyl salicylate and diphenhydramine, terbutaline, and salbutamol, were rapidly detected using nanoEESI-MS. A single sample analysis could be completed within 1.2 s. Tandem mass spectrometry was used to confirm the identification of important compounds in each aerosol drug sample. Reasonable relative standard deviation (RSD = 6.39%, n = 13) and acceptable sensitivity (10 ppt, 100 muL) were found for the salbutamol aerosol sample, which suggests that nanoEESI-MS has the quantitative capacity for analyzing complex pharmaceutical samples. This method was further extended to study the thermal decomposition process of salbutamol, showing that the degradation kinetics of salbutamol can be conveniently tracked. Our data demonstrate that nanoEESI tandem mass spectrometry is a fast and sensitive technique for the analysis of aerosol drug preparations, showing promising applications in pharmacology studies and in situ analysis of aerosol drugs on the market.