硫酸沙丁胺醇脉冲控释微丸的制备

目的制备硫酸沙丁胺醇脉冲控释微丸。方法采用挤出滚圆法制备载药丸芯 ,使用水溶胀性材料为内包衣溶胀层 ,乙基纤维素水分散体为外包衣控释层制备脉冲控释微丸 ,并考察溶胀层材料类型、十二烷基硫酸钠 (SDS)含量、溶胀层和控释层包衣增重量对药物释放的影响。结果药物通过控释层衣膜破裂而释放 ,溶胀层材料类型、内包衣层中SDS的加入与否、溶胀层和控释层厚度对脉冲控释微丸的释药时滞和释药速率均具有显著性影响。结论采用低取代羟丙基纤维素为溶胀性材料 ,并加入 0 0 5 2mol LSDS ,共同作为内包衣层 ,制备的脉冲控释微丸 ,当内包衣层和外包衣层增重均为 1 8%时 ,在模拟人体内胃肠道pH值变化条件下达到了时滞为 4 5h ,时滞后 1 5h累积释药 80 %以上的脉冲释药效果     

Analysis of salbutamol and related impurities by derivative spectrometry

Ultraviolet derivative spectrometry has been proposed for the analysis of salbutamol and related impurities. The assay of salbutamol aldehyde, 5-formyl-saligenin, and salbutamol ketone was performed in sodium hydroxide 0.1 mol/l solutions, using first and second derivative spectra. The method has been applied for the assay of related impurities of commercial samples of salbutamol sulfate.     

In vitro and in vivo studies of sustained-release floating dosage forms containing salbutamol sulfate

Peroral sustained-release floating capsules containing salbutamol sulfate were formulated using different combinations of hydrocolloids of natural and semi-synthetic origin. The floating properties and release rate characteristics were determined for the capsules in simulated gastric fluid USP XXI and HCl (0.1 mol.l-1) as dissolution media. Also, a marketed sustained-release non-floating capsule containing salbutamol sulfate was studied for its release rate characteristics. The floating capsule formulated showed a Higuchian release profile while the marketed product released only about 80% of the total dose in the stipulated 12 h in the dissolution medium. In vivo X-ray studies of the abdomen were carried out to locate the floating and non-floating (fabricated) dosage forms at various time intervals of uniform duration. The floating capsule definitely indicated a residence time (up to 8-9 h) in the stomach greater than for the non-floating capsule.     

Preformulation study of a poorly water-soluble drug, alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol: selection of the base for dosage form design

The physicochemical properties of the base and hydrochloride salt of the poorly water-soluble drug alpha-pentyl-3-(2-quinolinylmethoxy) benzenemethanol (REV 5901) were investigated in order to select an appropriate form of the drug for dosage form development. The pH-solubility profiles of both the base and the salt at 37 degrees C were identical and were in agreement with a pKa value of 3.67 determined by the UV spectral method. The solubility of the drug (approximately 0.002 mg/mL at pH 6) increased gradually with a decrease in pH and reached a value of 0.95 mg/mL at pH 1; at pH values less than 1, the solubility decreased due to the common-ion effect. The pHmax, i.e., the pH of maximum solubility of the drug was, therefore, 1.0. The role of the pHmax in the selection of a salt or base form of a compound was investigated. Due to the conversion of the salt to the base at the surface of the dissolving solid at pH values greater than pHmax, the dissolution rates of both the base and the salt were identical. In the solid state, the salt existed in anhydrous and monohydrate forms; the anhydrous salt converted to the hydrate at greater than 40% relative humidity, and the hydrate lost water at 40-60 degrees C. The thermal properties of the salt were indicative of its potential instability, which was confirmed by accelerated stability studies. The base existed in a stable crystalline solid form, and also in an oily liquid form which converted to crystals on standing.(ABSTRACT TRUNCATED AT 250 WORDS)     

联合吸入硫酸镁及沙丁胺醇治疗哮喘的临床研究

目的：探讨联合吸入7.5%等渗硫酸镁及1％沙丁胺醇对发作期哮喘患肺功能的影响。方法：将75例发作期哮喘患随机分成A、B、C3组，每组25人，A组雾化吸入7.5%等渗硫酸镁溶液3ml后间歇5min，再吸入生理盐水3ml。B组雾化吸入0.1%沙丁胺醇3ml后，间歇5min再吸入生理盐水3ml。C组雾化吸入0.1%沙丁胺醇3ml后，间歇5min再雾化吸入7.5%等渗硫酸镁溶液3ml。于吸药前、后15min分界和肺活量（FVC）、1秒钟用力呼气容积（FEV1）、最大呼气流量（PEF）的检测，并分别测A、C两组吸药前后收缩压、舒张压、心率、呼吸的变化。结果：3组吸药前后肺功能指标占其正常预计值的百分比浓度（FVC％、FEV1％、PEF％）比较均有显性差异（P＜0．05）；3组间吸药后15min肺功能比较：B组显高于A组（P＜0．05）；C组非常显高于B组（P＜0．01）和A组（P＜0．01）。A组及C组吸药前后收缩压、舒张率、心率和呼吸频率差异均无显性（P＞0．05）。结论：联合吸入7．5％等渗硫酸镁及1％沙丁胺醇对发作期哮喘患的治疗有协同作用，能明显改善通气功能，且对患的血压、心率、呼吸无明显影响。     

The effect of alkylpolyglycoside surfactants on the crystallization of spray-dried salbutamol sulphate: a GravimetricNear-Infrared Spectroscopy Study

This study monitored the effect of a series of structurally related surfactants on the crystallization of amorphous salbutamol sulphate. Amorphous salbutamol sulphate was prepared by spray drying from a solution in water and in the presence of various alkylpolyglycosides (APGs) at different concentrations. The particles were then analyzed using isothermal microcalorimetry and water vapor sorption (Dynamic Vapour Sorption, DVS) analysis combined with near-infrared spectroscopy (DVS-NIR). Both isothermal microcalorimetry and DVS-NIR were able to detect the transition from the amorphous to the crystalline state. The presence of APG surfactants modified the shape of the crystallization peak obtained using isothermal microcalorimetry. The gravimetric study combined with NIR revealed that while the crystallization was similar for the particles with or without surfactant, there was a great difference in the release of water from the newly formed crystal. In the presence of some of the surfactants tested, salbutamol sulphate released the water much faster than in the absence of surfactant. These results helped to explain the differences found in the isothermal microcalorimeter data. Differences were observed in the shapes of the NIR water peaks related to water due to the presence of the surfactant. In conclusion, the use of DVS combined with NIR has helped to analyze and understand the effect of APGs on the crystallization of amorphous salbutamol sulphate.     

The effect of alkylpolyglycoside surfactants on the crystallization of spray-dried salbutamol sulphate: a gravimetric near-infrared spectroscopy study

This study monitored the effect of a series of structurally related surfactants on the crystallization of amorphous salbutamol sulphate. Amorphous salbutamol sulphate was prepared by spray drying from a solution in water and in the presence of various alkylpolyglycosides (APGs) at different concentrations. The particles were then analyzed using isothermal microcalorimetry and water vapor sorption (Dynamic Vapour Sorption, DVS) analysis combined with near-infrared spectroscopy (DVS-NIR). Both isothermal microcalorimetry and DVS-NIR were able to detect the transition from the amorphous to the crystalline state. The presence of APG surfactants modified the shape of the crystallization peak obtained using isothermal microcalorimetry. The gravimetric study combined with NIR revealed that while the crystallization was similar for the particles with or without surfactant, there was a great difference in the release of water from the newly formed crystal. In the presence of some of the surfactants tested, salbutamol sulphate released the water much faster than in the absence of surfactant. These results helped to explain the differences found in the isothermal microcalorimeter data. Differences were observed in the shapes of the NIR water peaks related to water due to the presence of the surfactant. In conclusion, the use of DVS combined with NIR has helped to analyze and understand the effect of APGs on the crystallization of amorphous salbutamol sulphate.     

The degradation of salbutamol in ethanolic solutions

The degradation pathways of salbutamol in ethanolic solutions have been investigated and three potential ethyl ether degradation products have been identified. Two have been confirmed as salbutamol ethyl ethers and the third as a diethyl ether. All three degradation products have been structurally elucidated by LC–MS–MS (TOF and tandem quadrupole). The two ethyl ethers have a molecular weight of 267 Da (28 units higher than salbutamol) and are structural isomers (molecules with the same molecular weight but different structural arrangements). The molecular weight of the two ethyl ethers is consistent with the addition of one ethyl group to the salbutamol molecule and elimination of one water molecule. The molecular weight of the diethyl ether is 295 Da (56 units higher than salbutamol) and is consistent with the addition of two ethyl groups to the salbutamol molecule and elimination of two water molecules. A plausible degradation mechanism for the formation of the salbutamol ethyl ethers is the acid-catalysed dehydration of alcohols. Acidic pH is required to drive the degradation of salbutamol in ethanolic solution. Higher degradation levels of salbutamol ethyl ethers are achieved in acidic pH solutions. Levels of the two salbutamol ethyl ethers reach a maximum at an ethanol concentration of around 20%. Levels of the diethyl ether increase linearly with ethanol concentration, until it becomes the major degradation product in high concentration ethanolic solutions (≥30%).     

Dry powder aerosol generation in different environments: Performance comparisons of albuterol,albuterol sulfate,albuterol adipate and albuterol stearate

Aerosols formed by three salts and the free base of albuterol were compared following their formation from similarly micronized crystalline powders held in a model dry powder inhaler (DPI) under varying environmental conditions. Aqueous solubility at 22°C was the greatest for albuterol adipate diethanolate (353 mg/ml), followed by albuterol sulfate (250 mg/ml), albuterol free base (15.7 mg/ml) and albuterol stearate (0.6 mg/ml). Temperature and relative humidity (RH) of the air drawn through the inhaler was systematically varied in the range 20–45°C and 30–95% RH. Several inhaler performance outcomes were compared statistically between physical forms and across the applied environmental conditions. Significant differences (P < 0.05) existed between powder forms with respect to emptying of the metering disk, inhaler emptying, powder deaggregation, fine particle dose (mass < 6.4 μm aerodynamic diameter), and each compound's susceptibility to temperature and relative humidity. The free base emptied poorly from the inhaler compared to all salt forms. Inhaler emptying for all four compounds was unaffected by temperature and humidity over most environments tested (P > 0.05) although only albuterol adipate diethanolate and albuterol sulfate were insensitive at 94% RH and 45°C. At 20°C and 50% RH, the fine particle percent of the emitted doses [mean (experimental range)] were 77.7 (7.3)%, 63.6 (4.2)%, 9.0 (1.8)% and 55.7 (3.4)% for the free base, sulfate, adipate diethanolate and stearate salts of albuterol, respectively. Fine particle doses and percents of albuterol and albuterol sulfate decreased progressively with increasing relative humidity and temperature while albuterol adipate diethanolate and albuterol stearate aerosol performance remained largely unaffected; these latter salts showed changes in fine particle percents only at 45°C and 95% RH although the adipate diethanolate deaggregated very poorly under all conditions. Overall, albuterol stearate, the most hydrophobic salt, emptied and aerosolized best from the inhaler and showed least sensitivity to temperature and humidity. Neither solubility nor moisture sorption correlated directly with inhaler performance in high humidity environments, showing that the multiplicity of factors controlling the quality of the emitted aerosol from DPIs prevents straightforward prediction of optimal physical forms and mandates their experimental review. Nevertheless, salt selection is an important area to screen as new compounds are developed for inhalation and DPI device performance continues to improve.     

Bioavailability assessment of salbutamol sulfate suppositories in human volunteers

The purpose of this investigation was to evaluate the bioavailability of three salbutamol sulfate suppository formulations. The formulations were; 2 mg salbutamol sulfate in Suppocire NA base containing 6% Eudispert gel (F1), 2mg salbutamol sulfate in Witepsol H15 base containing 3% methyl cellulose gel (F2), and 2 mg salbutamol sulfate in Witepsol W25 base containing 3% methyl cellulose gel (F3). The formulations were administered via rectal route in six healthy male adult volunteers. The bioavailability of the three suppository formulations was compared with the oral bioavailability of salbutamol sulfate 2mg tablets (F4). Six volunteers participated in a four-way crossover study, where each study was separated from the other by an interval of 1 weak. Venous blood samples of 5 ml were taken immediately before dosing and after predetermined time intervals of 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 and 8 h. The result showed that Cmax +/- S.D. observed were 12.96 +/- 2.11, 14.78 +/- 2.33, 10.02 +/- 1.42 and 11.51 +/- 1.22 ng ml(-1) for F1, F2, F3 and F4, respectively. The Tmax +/- S.D. were found to be 1.91 +/- 0.20, 1.83 +/- 0.26, 2.50 +/- 0.00 and 2.67 +/- 0.24 h for F1, F2, F3 and F4, respectively. AUC +/- S.D. values were 40.25 +/- 1.88, 42.16 +/- 1.55, 28.62 +/- 1.98 and 37.63 +/- 1.44 ng h per ml for F1, F2, F3 and F4, respectively. The relative bioavailabilities of the investigated formulations were 112.04, 106.96 and 76.06 for formula F2, F1 and F3, respectively, when compared with the oral preparation (F4). The finding indicates that the bioavailability of salbutamol sulfate can be enhanced by delivering it rectally with Suppocire NA base containing 6% Eudispert gel or with Witepsol W25 base containing 3% methyl cellulose to match that of oral tablets. Salbutamol sulfate can be rectally administered in patients who are less compliant with the oral administration.     

Impact of process variables on the micromeritic and physicochemical properties of spray‐dried microparticles – Part II. Physicochemical characterisation of spray‐dried materials

Objectives In this work we investigated the residual organic solvent content and physicochemical properties of spray‐dried chlorothiazide sodium (CTZNa) and potassium (CTZK) salts. Methods The powders were characterised by thermal, X‐ray diffraction, infrared and dynamic vapour sorption (DVS) analyses. Solvent levels were investigated by Karl–Fischer titration and gas chromatography. Key findings Spray‐drying from water, methanol (MeOH) and mixes of MeOH and butyl acetate (BA) resulted in amorphous microparticles. The glass transition temperatures of CTZNa and CTZK were ～192 and ～159°C, respectively. These materials retained their amorphous nature when stored at 25°C in dry conditions for at least 6 months with no chemical decomposition observed. DVS determined the critical relative humidity of recrystallisation of CTZNa and CTZK to be 57% RH and 58% RH, respectively. The inlet temperature dependant oxidation of MeOH to formaldehyde was observed; the formaldehyde was seen to deposit within the amorphous matrix of spray‐dried product. Spray‐drying in the open blowing mode coupled with secondary drying resulted in a three‐fold reduction in residual BA (below pharmacopoeial permitted daily exposure limit) compared to spray‐drying in the closed mode. Conclusions Experiments showed that recirculation of recovered drying gas increases the risk of deposition of residual solvents in the spray‐dried product.     

硫酸沙丁胺醇油包水型口服纳米乳的制备及小肠吸收考察

目的研究硫酸沙丁胺醇油包水(W/O)型口服纳米乳的成乳条件及小肠吸收情况。方法采用两种制备方法考察不同制备条件对纳米乳形成的影响;采用伪三元相图法考察油相与司盘80的不同配比对成乳区域的影响,求出W/O型纳米乳形成区域;采用HPLC法测定纳米乳中硫酸沙丁胺醇的含量;采用大鼠在体小肠循环法初步考察该纳米乳的口服吸收情况。结果在本实验范围内,稳定且含水量较高、有实际应用价值的W/O型纳米乳的优化处方为豆油、司盘80、吐温80、蒸馏水的质量比为22.8∶22.8∶45.5∶8.9。根据最优处方,将水溶性药物硫酸沙丁胺醇溶于水相中,制得了W/O型纳米乳。大鼠在体小肠循环吸收试验初步证明了该纳米乳具有缓释作用。结论W/O型纳米乳可作为水溶性药物的缓控释制剂的载体。     

Simultaneous quantitative determination of salbutamol sulfate and bromhexine hydrochloride in drug preparations by difference spectrophotometry

A difference spectrophotometric procedure has been developed for the simultaneous determination of salbutamol sulfate (SS) and bromhexine hydrochloride (BH) in tablet preparations. The method comprised the measurements of the absorbance of a solution of the drug mixture in pH 2.0 buffer solution relative to that of an equimolar solution in 0.1 N methanolic NaOH at wavelengths of 310 and 280 nm. The presence of identical isosbestic points for pure drug solutions and sample solutions indicated the non-interference of excipients in the absorption at these wavelengths. Compliance with Beer's law was achieved in the concentration range of 0–100 μg/ml for SS and 0–200 μg/ml for BH at these wavelengths.     

The influence of exercise and dehydration on the urine concentrations of salbutamol after inhaled administration of 1600 µg salbutamol as a single dose in relation to doping analysis

The present study investigated the influence of exercise and dehydration on the urine concentrations of salbutamol after inhalation of that maximal permitted (1600 µg) on the 2015 World Anti‐Doping Agency (WADA) prohibited list. Thirteen healthy males participated in the study. Urine concentrations of salbutamol were measured during three conditions: exercise (EX), exercise+dehydration (EXD), and rest (R). Exercise consisted of 75 min cycling at 60% of VO_2max and a 20‐km time‐trial. Fluid intake was 2300, 270, and 1100 mL during EX, EXD, and R, respectively. Urine samples of salbutamol were collected 0–24 h after drug administration. Adjustment of urine concentrations of salbutamol to a specific gravity (USG) of 1.020 g/mL was compared with no adjustment. The 2015 WADA decision limit (1200 ng/mL) for salbutamol was exceeded in 23, 31, and 10% of the urine samples during EX, EXD, and R, respectively, when unadjusted for USG. When adjusted for USG, the corresponding percentages fell to 21, 15, and 8%. During EXD, mean urine concentrations of salbutamol exceeded (1325±599 ng/mL) the decision limit 4 h after administration when unadjusted for USG. Serum salbutamol C_max was lower (P<0.01) for R(3.0±0.7 ng/mL) than EX(3.8±0.8 ng/mL) and EXD(3.6±0.8 ng/mL). AUC was lower for R (14.1±2.8 ng/mL·?h) than EX (16.9±2.9 ng/mL·?h)(P<0.01) and EXD (16.1±3.2 ng/mL·?h)(P<0.05). In conclusion, exercise and dehydration affect urine concentrations of salbutamol and increase the risk of Adverse Analytical Findings in samples collected after inhalation of that maximal permitted (1600 µg) for salbutamol. This should be taken into account when evaluating doping cases of salbutamol. Copyright © 2015 John Wiley & Sons, Ltd.     

Physicochemical and in vitro deposition properties of salbutamol sulphate/ipratropium bromide and salbutamol sulphate/excipient spray dried mixtures for use in dry powder inhalers

The physicochemical and aerodynamic properties of spray dried powders of the drug/drug mixture salbutamol sulphate/ipratropium bromide were investigated. The in vitro deposition properties of spray dried salbutamol sulphate and the spray dried drug/excipient mixtures salbutamol sulphate/lactose and salbutamol sulphate/PEG were also determined. Spray drying ipratropium bromide monohydrate resulted in a crystalline material from both aqueous and ethanolic solution. The product spray dried from aqueous solution consisted mainly of ipratropium bromide anhydrous. There was evidence of the presence of another polymorphic form of ipratropium bromide. When spray dried from ethanolic solution the physicochemical characterisation suggested the presence of an ipratropium bromide solvate with some anhydrous ipratropium bromide. Co-spray drying salbutamol sulphate with ipratropium bromide resulted in amorphous composites, regardless of solvent used. Particles were spherical and of a size suitable for inhalation. Twin impinger studies showed an increase in the fine particle fraction (FPF) of spray dried salbutamol sulphate compared to micronised salbutamol sulphate. Co-spray dried salbutamol sulphate:ipratropium bromide 10:1 and 5:1 systems also showed an increase in FPF compared to micronised salbutamol sulphate. Most co-spray dried salbutamol sulphate/excipient systems investigated demonstrated FPFs greater than that of micronised drug alone. The exceptions to this were systems containing PEG 4000 20% or PEG 20,000 40% both of which had FPFs not significantly different from micronised salbutamol sulphate. These two systems were crystalline unlike most of the other spray dried composites examined which were amorphous in nature.     

Hydrochloride salt co-crystals: preparation,characterization and physicochemical studies

Co-crystallization approach for modification of physicochemical properties of hydrochloride salt is presented. The objective of this investigation was to study the effect of co-crystallization with different co-crystal formers on physicochemical properties of fluoxetine hydrochloride (FH). FH was screened for co-crystallization with a series of carboxylic acid co-formers by slow evaporation method. Photomicrographs and melting points of crystalline phases were determined. The co-crystals were characterized by FTIR, DSC and PXRD methods. Solubility of co-crystals was determined in water and buffer solutions. Powder and intrinsic dissolution profiles were assessed for co-crystals. Physical mixtures of drug and co-formers were used for comparisons at characterizations and physicochemical properties evaluation stages. Four co-crystals of FH viz. Fluoxetine hydrochloride-maleic acid (FH-MA), Fluoxetine hydrochloride-glutaric acid (FH-GA), Fluoxetine hydrochloride-L-tartaric acid (FH-LTA) and Fluoxetine hydrochloride-DL-tartaric acid (FH-DLTA) were obtained from screening experiments. Physical characterization showed that they have unique crystal morphology, thermal, spectroscopic and X-ray diffraction properties. Solubility and dissolution studies showed that Fluoxetine hydrochloride-maleic acid co-crystal possess high aqueous solubility in distilled water, pH 4.6, 7.0 buffer solutions and dissolution rate in distilled water than that of pure drug. Co-crystal formation approach can be used for ionic API to tailor its physical properties.     

Polycaprolactone microspheres as carriers for dry powder inhalers: effect of surface coating on aerosolization of salbutamol sulfate

This study reports the factors controlling aerosolization of salbutamol sulfate (SS) from mixtures with polycaprolactone (PCL) microspheres fabricated using an emulsion technique with polyvinyl alcohol (PVA) as stabilizer. The fine particle fraction (FPF) of SS from PCL measured by a twin-stage impinger was unexpectedly found to be zero, although scanning electron microscopy showed that the drug coated the entire microsphere. Precoating the microspheres with magnesium stearate (MgSt) excipient solutions (1%-2%) significantly increased (p < 0.05, n = 5) the FPF of SS (11.4%-15.4%), whereas precoating with leucine had a similar effect (FPF = 11.3 ± 1.1%), but was independent of the solution concentration. The force of adhesion (by atomic force microscopy) between the PCL microspheres and SS was reduced from 301.4 ± 21.7?nN to 110.9 ± 30.5 nN and 121.8 ± 24.6 nN, (p < 0.05, n = 5) for 1% and 2% MgSt solutions, respectively, and to 148.1 ± 21.0 nN when coated with leucine. The presence of PVA on the PCL microspheres (detected by X-ray photoelectron spectroscopy) affected the detachment of SS due to strong adhesion between the two, presumably due to capillary forces acting between them. Precoating the microspheres with excipients increased the FPF significantly by reducing the drug-carrier adhesion.     

氧气吸入沙丁胺醇佐治毛细支气管炎

目的：探讨氧气吸入沙丁胺醇佐治毛细支气管炎的疗效。方法：采用随机对照观察，治疗组32例毛细支气管炎用氧气驱动吸入沙丁胺醇治疗。对照组31例用利巴韦林超声雾化吸入治疗。结果：治疗组咳嗽、喘憋及肺部罗音消失时间均小于对照组。结论：氧气吸入沙丁胺醇治疗毛细支气管炎起效快，疗效明显，副作用少。     

硫酸镁联合硫酸沙丁胺醇对重度支气管哮喘急性发作患儿肺功能的影响

目的 探讨硫酸镁联合硫酸沙丁胺醇对重度支气管哮喘急性发作患儿肺功能的影响.方法 选择本院2015年1月至2016年6月期间收治的60例重度支气管哮喘急性发作患儿作为观察对象,随机分为观察组和对照组,每组30例.对照组采用硫酸沙丁胺醇治疗,观察组予以硫酸镁联合硫酸沙丁胺醇治疗,治疗1周后比较两组治疗效果、康复指标(哮鸣音、气短、咳嗽)、住院时间、肺功能指标[最大呼气流量(PEF)、1秒用力呼气容积(FEV1)、用力肺活量(FVC)]与不良反应.结果 观察组总有效率为96.67％,显著高于对照组的70.00％,差异有统计学意义(x 2=7.680,P＜0.05);治疗后与对照组相比,观察组哮鸣音消失时间[(1.04±0.35)d]、气短消失时间[(2.11±1.25)d]、咳嗽消失时间[(3.75±1.08)d]及住院时间[(5.28±1.53)d]均较短,差异均有统计学意义(均P＜0.05);两组治疗前的肺功能指标比较差异均无统计学意义(均P＞ 0.05);治疗后两组FEV1、PEF、FVC水平均显著升高,且观察组上升趋势更为显著,差异均有统计学意义(均P＜ 0.05);两组患儿不良反应发生率比较差异无统计学意义(x 2=0.267,P＞0.05).结论 与单纯采用硫酸沙丁胺醇治疗重度支气管哮喘急性发作相比,硫酸镁联合硫酸沙丁胺醇治疗效果更加确切,且不良反应较少,对改善患儿临床症状与肺功能均具有积极作用,值得临床进一步推广应用.     

Stability of ipratropium bromide and salbutamol nebuliser admixtures

The physicochemical stability of an admixture of ipratropium bromide and salbutamol nebuliser solutions, 1:1 v/v, was determined by storing solutions for five days in a refrigerator at 4C, at 22C protected from light and at 22C under 24 hour fluorescent lighting. Concentrations of ipratropium and salbutamol were periodically determined using a high performance liquid chromatography assay. The nebuliser solution admixtures retained greater than 90 per cent of their original concentrations of ipratropium and salbutamol for the duration of the study. Differences in losses between storage conditions were not statistically significant. Admixtures of proprietary ipratropium bromide and salbutamol nebuliser solutions (1:1 v/v) retain greater than 90 per cent of their initial concentrations if stored between 4C and 22C for periods of up to five days. An expiry period of five days for these admixtures would seem reasonable in practice.