Estudio aleatorizado, cruzado, de no inferioridad para evaluar la eficacia, la seguridad y la tolerabilidad de dos formulaciones de budesonida/fumarato de formoterol en adultos asmáticos / Randomized, Crossover, Non-Inferiority Study to Evaluate the Efficacy, Safety and Tolerability of Two Budenoside/Formoterol Fumarate Formulations in Asthmatic Adults

RESUMEN El asma es un grave problema de salud mundial. Según el último informe del Ministerio de Salud, 1 380 000 sujetos padecen asma en la Argentina.1 Las guías internacionales (Europa, Estados Unidos, OMS) varían en su enfoque para definir la equivalencia y la posibilidad de intercambio de los productos para inhalación respiratorios. Si bien es posible un enfoque in vitro, en general las guías recomiendan brindar más indi cios clínicos que avalen la posibilidad de intercambiar el producto innovador por otro posteriormente desarrollado con iguales principios activos en polvo seco para inhalar. Este estudio, aleatorizado de fase IV, se realizó para establecer la eficacia, seguridad y tolerabilidad de Neumoterol® 400 en comparación con el producto medicinal de refe rencia Symbicort forte budesonida/fumarato de formoterol 320/9 μg, indicados 2 veces al día en pacientes asmáticos. Además, se evaluó la preferencia de los pacientes por uno u otro dispositivo. Se demostró la no inferioridad de la formulación evaluada en comparación con el pro ducto medicinal de referencia. El límite inferior del IC del 95% para la diferencia entre los tratamientos fue mayor que el margen predefinido de no inferioridad de -125 mL (diferencia: 0,044 l [IC del 95%: -0,008 a 0,096]). Asimismo, se comprobaron valores más altos para el AUC0-10h del FEV1 y un mayor cambio respecto del puntaje basal en la prueba de control del asma el día 29 para las cápsulas de budesonida/fumarato de formoterol 400/12 μg. En un análisis exploratorio sobre la preferencia de los pacientes por los dispositivos, una mayor proporción de participantes expresaron su preferencia global por la cápsula de budesonida/fumarato de formoterol 400/12 μg. No se informa ron diferencias en la incidencia de AE o SAE (del inglés Adverse event: evento adver so y Severe Adverse Event: evento adverso severo) graves durante el tratamiento o después de este. El perfil de seguridad de ambos productos en general concordó con el perfil comprobado de budesonida/fumarato de formoterol.

ABSTRACT Asthma is a serious worldwide health problem. According to the last report of the Min istry of Health, 1,380,000 subjects suffer from asthma in Argentina.1 The International Guidelines (Europe, United States, WHO [World Health Organization]) have varying approaches to define the equivalence and possibility of switching respiratory inhalation products. Whereas an in vitro approach is possible, in general Guidelines recommend providing more clinical evidence that support the possibility of switching from the inno vative product to another one subsequently developed with the same active ingredient in the form of dry powder inhaler. This randomized, phase IV study has been conduct ed to establish the efficacy, safety and tolerability of Neumoterol® 400 compared to the reference medicinal product Symbicort forte, budenoside/formoterol fumarate 320/9 μg twice a day in asthmatic patients. Also, the patients' preference for one device or the other has been evaluated. The evaluated formulation has proven to be non-inferior compared to the reference medicinal product. The lower 95% CI (confidence interval) limit for the difference be tween treatments was higher than the predefined non-inferiority margin of -125 mL (difference: 0.044 l [95% CI: -0.008 to 0.096]). Also, higher values were evidenced for the AUC0-10h (are under the curve) of the FEV1 (forced expiratory volume in the first second) and a more important change of the baseline score in the asthma control test on day 29 for the budenoside/formoterol fumarate capsules of 400/12 μg. In one exploratory test about the patients' preference for one device or the other, a higher pro portion of participants expressed their global preference for the budenoside/formoterol fumarate capsule of 400/12 μg. No differences were reported in the incidence of AEs (adverse events) or SAEs (serious adverse events) during or after the treatment. The safety profile of both products in general agreed with the verified profile of budenoside/ formoterol fumarate.

Research Progress of Pulmonary Drug Delivery System / 医药导报

The pulmonary drug delivery system is a new drug delivery system developed in recent decade.Its composi-tion and mode of administration are obviously different from those of the general preparation.The advantages of pulmonary drug de-livery system include high local drug concentration,no first pass effect and fast drug absorption.Currently,it has become an impor-tant means of treating lung diseases and promoting the drug absorption of macromolecules.The drug categories,excipients,inhala-tion devices and clinical application of pulmonary drug administration were analysed by literature reviews.Furthermore,the re-search progress and characteristics of pulmonary drug delivery system in recent years were also summarized,which provide refer-ence for further study of pulmonary drug delivery.

Clinical Observation of Salmeterol Fluticasone Combined with Tiotropium Bromide in the Treatment of COPD via Different Inhalation Devices / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of salmeterol fluticasone combined with tiotropium bromide in the treatment of COPD via different inhalation devices.METHODS:Eighty COPD patients were selected from our hospital during Jan.2014 to Jan.2015,and then divided into trial group and control group according to random number table,with 40 cases in each group.Both groups were given Salmeterol fluticasone inhalant 500 μg,bid+Tiotropium bromide inhalant 18 μg,qd.Control group was given medicine via inhalation device coming with medicine,while trial group was given medicine via gas compression type ultrasonic spray inhalator.Both groups were treated for 1 year.Blood concentration of medicine 0.5 h after medication,mMRC score and COPD acsessment test (CAT) score 3,6,9 months after treatment,the times of acute exacerbation during treatment,FEV1％ before and af ter treatment were all observed in 2 groups.The occurrence of ADR was recorded.RESULTS:Four cases withdrew from trial group and 1 case from control group.After medication,there was no statistical significance in blood concentration of fluticasone,salmeterol and tiotropium bromide between 2 groups (P＞0.05).0.5 h after medication,mMRC score of trial group was slightly lower than that of control group,without statistical significance (P＞0.05);CAT score of it was significantly lower than that of control group,with statistical significance (P＜0.05).The times of acute exacerbation in trial group during treatment was significantly less than control group,with statistical significance (P＜0.05).The decrease of FEV1％ in trial group was slightly lower than control group,without statistical significance (P＞0.05).The incidence of ADR in trial group was significantly lower than control group,with statistical significance (P＜0.05).CONCLUSIONS:For COPD patients,salmeterol fluticasone combined with tiotropium bromide via gas compression type ultrasonic spray inhalator is better than inhalation device coming with medicine in clinical efficacy and safety.

Simulation and validation of computational fluid dynamics used for selected inhalation device of Rehmanniae Radix oligosaccharide dry powder inhalation / 中草药

Objective: To simulate the kinematics of drug particles in two kinds of dry powder inhalation devices for Rehmanniae Radix oligosaccharide dry powder inhalation (RRODPI) by computational fluid dynamics (CFD), and to compare simulation results with the in vitro deposition results in order to verify the accuracy of the results. Methods: NGI was used to carry out in vitro deposition experiments, and the relative experiment data were obtained. UGNX 10.0 software was adopted to establish three-dimensional models of two kinds of dry powder inhalation devices according to their actual sizes, and then the models were imported into ICEM CFD software to divide mesh. After checking mesh quality, mesh was imported to Fluent software and the related parameters were set. When the data was in steady state after iteration and convergence, the data analysis was carried out; Finally the kinematics results of drug particles at three kinds of particle sizes in two kinds of dry powder inhalation devices were gained. The kinematics results were compared with the in vitro deposition results to verify the simulation results. Results: In vitro deposition experiment results showed that the effective deposition rate in twister was higher than that in osmohaler. CFD results showed that drug particles at different sizes in twister could all reach the outlet but for drug particles in osmohaler, it could not reach the outlet at a certain range of sizes. The two results showed that twister was more suitable for the dry powder inhaler device of RRODPI. Conclusion: It is comparatively intuitive to use CFD to carry out the kinematics simulation of drug particles in two kinds of dry powder inhalation devices and the result is consistent with the in vitro deposition experiment results, which can well predict the motion state of drug particles in the two dry powder inhalation devices.

Study Progress in Inhalation Drug Delivery Systems / 中国药师

Objective:To review the research progress and practical achievements in inhalation drug delivery systems. Methods:Based on the recently published papers and international conference papers,the research on the application of inhalation drug delivery systems was summarized and analyzed. Results:The advantages of inhalation drug delivery systems were illustrated. The advantages and drawbacks of different inhalation devices were reviewed,the guidelines for the selection and application were introduced,and the development direction of inhalation therapy was reviewed as well. Conclusion:Inhalation drug delivery systems show good application prospect.