盐酸溴己新吸入粉雾剂的质量与稳定性考察

摘 要 目的：评价自制的盐酸溴己新吸入粉雾剂的质量并考察其稳定性。方法: 采用冷冻干燥 气流粉碎法制备盐酸溴己新吸入粉雾剂,考察其吸湿性及临界相对湿度;测定其粒径和水分并观察粉末形态;检查其细微粒子剂量和递送剂量均一性;开展盐酸溴己新吸入粉雾剂稳定性考察。结果:所制备的盐酸溴己新吸入粉雾剂的临界相对湿度为65%,空气动力学粒径<5 μm,粉末含水量<2%,细微粒子剂量＞30%,递送剂量均一性符合药典要求;稳定性试验中各指标在观察期内无明显变化。结论:所制备的盐酸溴己新吸入粉雾剂适合肺部吸入给药,且具有较好的稳定性。     

吸入用乙酰半胱氨酸溶液雾化特性的体外评价

目的 研究吸入用乙酰半胱氨酸溶液的雾化特性,建立体外评价方法。方法 使用呼吸模拟装置对吸入用乙酰半胱氨酸溶液的递送速率和递送总量进行研究,使用新一代药用多级撞击器（NGI）测定空气动力学粒径分布。结果 不同雾化装置检测递送速率和递送总量数据存在明显差异,但使用同品牌雾化装置时吸入用乙酰半胱氨酸溶液自制样品和参比制剂的递送速率和递送总量无明显差异。不同雾化装置检测空气动力学粒径分布数据存在明显差异,但是使用同一品牌雾化装置,吸入用乙酰半胱氨酸溶液自制样品与参比制剂无明显差异。结论 所测定的体外数据描述了吸入用乙酰半胱氨酸溶液的体外特征,可为该制剂的体外评价提供参考。     

肺部吸入制剂评价方法研究进展

肺部吸入制剂在治疗肺炎、哮喘、慢性阻塞性肺病（COPD）等肺部疾病中的应用广泛。肺部吸入制剂主要包括吸入气雾剂、干粉吸入剂、吸入喷雾剂和吸入溶液,其体外评价方法主要包括递送剂量及递送剂量均一性,空气动力学粒径分布,喷雾模式和喷雾形态;体内评价方法主要包括药动学研究与放射性核素成像。就肺部吸入制剂的体内外评价方法的研究进展进行综述。     

硫酸沙丁胺醇吸入气雾剂的喷雾模式和喷雾形态的测定及群体生物等效分析

目的:测定定量型吸入气雾剂参比制剂和受试制剂各3批的喷雾模式和喷雾形态、递送剂量，判断参比制剂和受试制剂体外雾化形态和剂量的等效性。方法:采用激光成像系统测定硫酸沙丁胺醇吸入气雾剂的喷雾模式和喷雾形态，以喷射角度和喷射宽度作为喷雾形态的评价参数，以椭圆比和喷射面积作为喷雾模式的评价参数，对结果进行体外群体等效性分析。结合递送剂量测定结果，判断参比制剂和受试制剂的体外等效性。结果:参比制剂和受试制剂喷射角度几何平均值的比值分别为98.2%(3 cm)、97.1%(6 cm),喷射宽度几何平均值的比值分别为97.4%(3 cm)、98.4%(6 cm),对3 cm和6 cm处的椭圆比、喷射面积、喷射角度、喷射宽度分别进行群体等效分析，得到各参数的95%置信区间的上限值，椭圆比均为-0.02(3 cm和6 cm),喷射面积分别为-0.01(3cm)和-0.02(6 cm),喷射角度均为-0.02(3 cm和6 cm),喷射宽度均为-0.02(3 cm和6 cm)。参比制剂和受试制剂的递送剂量相差较大，受试制剂的递送剂量均一性较好。结论:参比制剂和受试制剂在喷雾模式和喷雾形态项目评价为等效，但...     

异丙托溴铵雾化吸入为主三联治疗慢阻肺急性加重期疗效观察

摘 要 目的： 探讨异丙托溴铵雾化吸入为主三联治疗慢性阻塞性肺疾病急性加重期（AECOPD）的临床疗效及安全性。方法: AECOPD患者150例随机分为两组各75例,对照组给予布地奈德+沙丁胺醇雾化吸入,观察组在此基础上加用异丙托溴铵雾化吸入治疗。比较两组患者临床疗效、治疗前后呼吸困难评分、肺功能指标水平、血气分析指标水平及药品不良反应发生率等指标。结果: 观察组临床总有效率显著优于对照组（P<0.05）。两组患者治疗后呼吸困难评分、肺功能指标及血气分析指标均较治疗前有显著改善（P<0.05）,且观察组患者上述指标均显著优于对照组（P<0.05）。两组药品不良反应发生率比较,差异无统计学意义（P＞0.05）。结论:异丙托溴铵雾化吸入为主三联治疗AECOPD患者可有效缓解临床症状体征,改善肺部通气功能,提高临床疗效,且未增加不良反应发生风险。     

2018—2020年咸阳市中心医院肺部吸入制剂的应用情况分析

目的 分析咸阳市中心医院吸入制剂应用情况,为患者及临床使用提供参考。方法 对2018—2020年咸阳市中心医院肺部吸入制剂的种类、销售额、用药频度（DDDs）、日均费用（DDC）和药品使用排序比（B/A）进行统计分析。结果 2018—2020年咸阳市中心医院肺部吸入制剂的用药金额呈逐年上升趋势,总金额的构成比基本保持稳定。其中总金额排前3位的制剂分别为吸入用布地奈德混悬液、布地奈德福莫特罗粉吸入剂、吸入用复方异丙托溴铵;DDDs排名前3位的制剂分别是布地奈德福莫特罗粉吸入剂、吸入用布地奈德混悬液、噻托溴铵粉吸入剂;DDC排名前3位的制剂分别是吸入用复方异丙托溴铵溶液、吸入用布地奈德混悬液、布地奈德福莫特罗粉吸入剂;B/A值均低于2。结论 2018—2020年度咸阳市中心医院肺部吸入制剂使用及价格结构较为合理。     

沙丁胺醇加异丙托溴铵治疗喘息性支气管炎

目的:观察空气压缩泵雾化吸入沙丁胺醇加异丙托溴铵治疗婴幼儿喘息性支气管炎的效果.方法:喘息性支气管炎患儿74例,分为治疗组35例,以空气压缩泵雾化吸入0.5%沙丁胺醇0.25 mL&#8226;次 1和0.025%异丙托溴铵0.5 mL&#8226;次 1加0.9%氯化钠溶液至2～3 mL,空气压缩泵雾化吸入,bid,每次10～15 min,疗程3～7 d;对照组39例,不加雾化.两组患儿其他治疗均相同.结果:治疗组有效率94.3%,对照组有效率64.1%(P＜0.01).结论:沙丁胺醇加异丙托溴铵雾化吸入治疗婴幼儿喘息性支气管炎能减轻症状,缩短病程,改善预后.     

异丙托溴铵雾化液联合3%高渗盐水辅助治疗小儿毛细支气管炎的临床观察

目的 观察异丙托溴铵雾化液联合3%高渗盐水辅助治疗小儿毛细支气管炎的临床疗效。方法 选取2010年1月-2013年10月诸城市妇幼保健院收治的毛细支气管炎患儿168例,随机分为对照组和治疗组,每组各84例。所有患儿常规性进行吸氧、抗病毒、抗炎、止咳、退热、化痰及激素治疗。对照组在常规性治疗基础上雾化吸入3%高渗盐水,3 mL/次,3～4次/d。治疗组雾化吸入异丙托溴铵雾化液联合3%高渗盐水,3 mL/次,3～4次/d。两组均持续治疗14 d。观察两组的临床疗效,比较两组患儿喘憋消失时间,哮鸣音消失时间,肺部X线影像好转时间和住院时间。结果 治疗组和对照组的总有效率分别为95.24%、84.52%,两组比较差异有统计学意义（P<0.05）。治疗后,治疗组喘憋消失、哮鸣音消失、肺部X线影像好转及住院时间均显著短于对照组,两组比较差异有统计学意义（P<0.05）。结论 异丙托溴铵雾化液联合3%高渗盐水辅助治疗小儿毛细支气管炎具有较好的临床疗效,可明显改善患儿的症状、体征,值得临床推广应用。     

助悬剂用量对糠酸氟替卡松鼻喷剂喷雾特性的影响

目的 研究混悬型鼻喷剂中助悬剂Avicel^®浓度对鼻喷剂喷雾模式、喷雾形态以及雾滴粒径的影响。方法 制备不同Avicel^®浓度的糠酸氟替卡松鼻用混悬液。通过SprayVIEW^®喷雾测试系统测试鼻喷剂的喷雾特性参数,使用Box-Behnken响应面法分析Avicel^®浓度对鼻喷剂体外喷雾特性的影响,同时考察Avicel^®浓度对喷雾雾滴粒径的分布影响以及在不同检测距离下雾滴的粒径变化。结果 增大Avicel^®浓度会显著减小喷雾面积以及喷雾角度和宽度（P<0.001）,同时增大D₅₀和整体粒径。增大驱动速度会显著增大喷雾面积、喷雾角度和宽度（P<0.05）,驱动加速度对喷雾特性的影响远小于Avicel^®浓度和驱动速度。随着检测距离的增加,雾滴粒径分布变得更加集中,雾滴粒径分布跨度变小。结论 本研究通过Box-Behnken响应面法发现Avicel^®的浓度与驱动速度对喷雾特性的影响存在拮抗作用,为鼻喷剂Avicel^®浓度的选择以及装置推荐驱动参数提供了参考。     

不同方法雾化吸入布地奈德及复方异丙托溴铵治疗儿童喘息性支气管炎疗效观察

目的:观察比较氧气驱动与空气压缩泵两种方法雾化吸入布地奈德混悬液及复方异丙托溴铵溶液治疗儿童喘息性支气管炎的疗效。方法:选择喘息性支气管炎患儿75例,将其随机分成3组,每组25例,三组均采用常规治疗方法,对照组未予雾化吸入,治疗A组采用空气压缩泵雾化吸入布地奈德混悬液及复方异丙托溴铵溶液,治疗B组采用氧气驱动雾化吸入相同药物。观察三组疗效、症状、体征变化情况。结果:治疗A、B两组总有效率分别为88.0%、96.0%均高于对照组(P<0.05)。气喘缓解时间治疗A、B两组均较对照组短(P<0.05),而治疗B组又相对短于治疗A组(P<0.05)。第一次雾化吸入后血氧饱和度(SaO2)与吸入前相比,治疗A组无明显变化(P>0.05),但治疗B组有明显上升(P<0.01)。结论:氧气驱动与空气压缩泵雾化吸入布地奈德混悬液及复方异丙托溴铵溶液均是治疗儿童喘息性支气管炎的有效方法,但氧气驱动雾化吸入治疗效果优于空气压缩泵雾化吸入。     

Validity of in Vitro Tests on Aqueous Spray Pumps as Surrogates for Nasal Deposition

Purpose. To determine whether deposition pattern is related to in vitromeasurements of droplet size, plume geometry, and spray pattern between two different nasal spray pumps believed to have different performance characteristics. Methods. Ten healthy volunteers inhaled radiolabeled saline from two different spray pumps (pump A and pump B). Deposition pattern was quantified from lateral views of the nose by gamma scintigraphy, expressed as the ratio of anterior to posterior (I:O) and superior to inferior (U:L) deposition. Droplet size was determined by Malvern Mastersizer S. Spray patterns were determined at 2.5 and 5 cm from the tip of the spray nozzle. Two-dimensional images of the emitted plume were captured by high-speed still photography. Results. There were no significant differences in I:O or U:L ratios for pump A compared to pump B, indicating no significant differences in deposition pattern. The volume diameters, D_v10 and D_v50, were not statistically different for pump A compared to pump B. There was a significant difference in D_v90 between pump A and pump B, (86.9 ± 5.8 m and 77.4 ± 2.4 m, respectively; P < 0.001). The ratio of the longest to shortest diameter for the spray pattern with pump A was 1.26 ± 0.06 at 2.5 cm and 1.44 ± 0.08 at 5 cm. The ratio for pump B was 1.13 ± 0.03 at 2.5 cm and 1.19 ± 0.05 at 5 cm. Ratios at both heights were statistically different for pump A compared to pump B (P < 0.00002 and P < 0.000001, respectively) Plume geometry analysis indicated statistical differences in both the width (17.0 ± 0.97 vs. 18.5 ± 0.56 cm, respectively; p<0.001) and the maximum length of the plumes (46.0 ± 1.83 vs. 53.1 ± 4.88 cm, respectively; p < .002). The differences in velocity of the plume and spray angle between the two pumps were not statistically different. Conclusions. Certain in vitrotests detected performance differences between the two pumps. However, these differences did not translate into different deposition patterns in vivo.     

Formulation and development of metered dose inhalations of salbutamol in solution form

In the present study attempts were made to prepare metered dose inhalation of salbutamol in solution form and compared it with the marketed metered dose inhalation in suspension form. Solution form of the drug was found better than marketed suspension formulation with respect to homogeneity and content uniformity. Propellant blend P-11 and P-12 in the proportion 30:70 was selected as it gave optimum vapour pressure. Surfactant oleic acid in concentration 10 mg per can was selected as it gave best results with clarity, spray pattern, vapour pressure, content per spray and rate of evaporation. Ethyl alcohol 2 ml per can was used as a cosolvent to give a clear solution, optimum vapour pressure, maximum content per spray and fair rate of evaporation. The selected formulation was subjected to the physico-chemical evaluation tests as per the standard pharmacopoeial procedures and the characteristics of the formulations were further compared with a conventional marketed formulation. In vitro study reveled the net respirable fraction was better than marketed preparation.     

喷雾模式及喷雾形态用于口腔吸入及鼻用制剂的质量评价

口腔吸入及鼻用制剂（orally inhaled and nasal drug products,OINDPs）是指将药物制备成干粉或雾滴,利用给药装置,分别将药物运送至肺部或鼻腔黏膜,进而发挥局部或全身治疗作用的剂型。喷雾模式和喷雾形态是溶液及混悬型吸入及鼻用制剂体外评价的重要指标,可以采用激光成像系统进行测定。对喷雾模式及喷雾形态的测定方法和结果评价进行了详细讨论,同时对激光成像系统中自动触发器模块的参数选择进行了相关说明。     

A novel metered dose transdermal spray formulation for oxybutynin

The objective of the present work was to develop a metered dose spray formulation for transdermal delivery of oxybutynin and to carry out the in vitro characterization of the optimized formulation. Oxybutynin release from a series of ethanol/acetone/methylal based formulations was assessed in vitro and the developed formulation was used for delivery from a metered dose spray. Various qualitative and quantitative parameters like spray pattern, particle size distribution, pH, evaporation time, pump seal efficiency test, average weight per metered dose, content per spray and content uniformity were evaluated. The different film forming agents were assessed and carbopol (0.5%) and lutrol (0.1%) were found to give good clarity of solution, evaporation rate, spray pattern and tackiness of the film. Diffusion studies of the optimized formulations through the semipermeable membrane showed the release of drug to the extent of almost 50% over a period of 24 h. Stability studies were conducted as per ICH guidelines and indicated that formulations were stable. Skin irritation studies were performed using rabbit as an animal model. The results obtained show that the metered dose transdermal spray formulation can be a promising and innovative therapeutic system for the transdermal administration of oxybutynin.     

五淋化石丸联合黄酮哌酯治疗慢性非细菌性前列腺炎的临床研究

目的探讨五淋化石丸联合黄酮哌酯治疗慢性非细菌性前列腺炎的临床疗效。方法选取2018年1月—2020年1月在驻马店市中心医院泌尿一科住院治疗的134例慢性非细菌性前列腺炎患者,随机分成对照组(n=67)和治疗组(n=67)。对照组口服盐酸黄酮哌脂片,0.2g/次,3次/d。治疗组在对照组的基础上口服五淋化石丸,5丸/次,3次/d。两组均同时治疗7d。观察两组的临床疗效,比较两组治疗前后NIH-CPSI评分和血清炎性因子的变化情况。结果治疗后,治疗组总有效率97.01%显著高于对照组的74.63%(P<0.05)。治疗后,两组疼痛症状评分、排尿症状评分、生活质量评分均显著降低(P<0.05);治疗后,治疗组NIH-CPSI评分显著低于对照组(P<0.05)。治疗后,两组患者白细胞介素4(IL-4)、白细胞介素8(IL-8)、肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)水平均显著降低(P<0.05);治疗后,治疗组血清炎性因子水平低于对照组(P<0.05)。结论五淋化石丸联合黄酮哌酯治疗慢性非细菌性前列腺炎临床疗效显著,能有效改善尿频、尿急、尿痛等症状,降低炎症因子的水平,值得临床借鉴与参考。     

Once-daily glycopyrronium bromide (Seebri Breezhaler®) for the treatment of chronic obstructive pulmonary disease (COPD)

Introduction: Long-acting bronchodilators are the mainstay of pharmacological therapy for patients with chronic obstructive pulmonary disease (COPD). The choice of optimal bronchodilator therapy for COPD is increasingly difficult for clinicians as new treatments are marketed.Areas covered: Inhaled glycopyrronium bromide (Seebri Breezhaler®) is a well-tolerated long-acting anti-muscarinic agent (LAMA) with a fast onset of action. In patients with moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of FEV₁, use of relief medication, day-time dyspnea scores, and probably also on health status. Furthermore, glycopyrronium bromide also has beneficial effects on dynamic hyperinflation and, probably by that, exercise tolerance. Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, although as a secondary outcome only. Expert opinion: Once-daily inhaled glycopyrronium bromide has positive impact on important COPD outcomes, comparable to the effects of other marketed LAMAs. Once-daily administration may improve adherence, and glycopyrronium bromide has the potential for a role in the future management of COPD similar to that of other long-acting anti-muscarinic agents, including tiotropium. Studies of glycopyrronium bromide with exacerbation rate as the primary outcome of interest is needed.     

The influence of actuation parameters on in vitro testing of nasal spray products

Nasal spray drug products are normally characterized via measurement of shot weight, spray pattern, plume geometry, and droplet size distribution (DSD). In this project, the actuation parameters, such as stroke length, actuation velocity, and actuation acceleration, were investigated to ascertain how they affect nasal spray characteristics. Pfeiffer nasal spray pump units filled with water were used in the study. Actuation parameters were adjusted using an electronic automated actuation system, SprayVIEW NSx. Spray pattern and plume geometry measurements were carried out using a high speed optical spray characterization system, SprayVIEW NSP, and DSD analysis was performed using a Malvern 2600 laser diffraction system. Our results show that different actuation parameters affect the nasal spray characteristics in different ways and to different degrees. Among all the actuation parameters, stroke length and actuation velocity have significant effects on the nasal spray characteristics, while the other actuation parameters have little, if any, effect. Compared to spray pattern, plume geometry and DSD, shot weight provides very little characterization information. The findings from this work suggest that, for in vitro bioavailability (BA) and bioequivalence (BE) studies of nasal spray products, the actuation parameters, stroke length, and velocity must be carefully selected. Spray pattern, plume geometry, and DSD appear to provide critical data for assessment of nasal pump performance.