Kenyon C J, Dewsbury N J, Newman S P
Pharmaceutical Profiles Ltd, Nottingham, UK.
Thorax. 1995 Aug;50(8):846-50. doi: 10.1136/thx.50.8.846.
The equivalence of generic beclomethasone dipropionate (BDP) formulations with their innovator counterpart must be demonstrated if generic formulations are to be used. This study has examined the aerodynamic particle size distributions of both innovator and generic formulations of BDP and the effect of a large volume spacer (Volumatic) on these distributions.
Aerosol clouds of three formulations of BDP delivering 250 micrograms per metered dose were characterised using a high precision multistage liquid impinger, and the amount of drug in different particle size bands was determined by spectrophotometric assay.
The mean (SD) respirable fractions of Becloforte, Beclazone, and Filair without the spacer (n = 10) were 24.1 (2.1)%, 23.1 (2.7)%, and 23.0 (2.1)% respectively; however, the ratio of deposition on stage 4 of the impinger to that on stage 3 was lower for Beclazone and for Filair than for Becloforte, implying a smaller proportion of fine particles for the generic products. When the three products delivered via the Volumatic spacer device were compared, the respirable fraction for Becloforte (n = 10) was 25.0 (4.0)%, but those of Beclazone (n = 10) and Filair (n = 11) were 16.0 (1.9)% and 14.6 (3.4)%. Repeat testing (n = 5) at a later date showed higher mean respirable fractions for all three products, but a trend towards the highest respirable fraction for Becloforte, and the same rank order for the other two products.
These in vitro findings suggest that the particle size distributions of the two generic formulations of BDP are not equivalent to that of the innovator product. Some differences in particle size distributions might not have been detected by a twin impinger. Clinical testing would be required to assess the therapeutic equivalence of innovator and generic corticosteroid products used with or without spacer devices.
如果要使用丙酸倍氯米松（BDP）的仿制药，必须证明其与原研产品的等效性。本研究考察了BDP原研产品和仿制药的空气动力学粒径分布，以及大容量储雾罐（Volumatic）对这些分布的影响。
使用高精度多级液体冲击器对三种每揿剂量为250微克的BDP制剂的气溶胶云进行表征，并通过分光光度法测定不同粒径范围内的药物量。
不含储雾罐时，必可酮、倍氯米松气雾剂和费里奈德的平均（标准差）可吸入分数（n = 10）分别为24.1（2.1）%、23.1（2.7）%和23.0（2.1）%；然而，倍氯米松气雾剂和费里奈德在冲击器第4阶段的沉积量与第3阶段沉积量的比值低于必可酮，这意味着仿制药的细颗粒比例较小。当比较通过Volumatic储雾罐装置递送的三种产品时，必可酮（n = 10）的可吸入分数为25.0（4.0）%，而倍氯米松气雾剂（n = 10）和费里奈德（n = 11）的可吸入分数分别为16.0（1.9）%和14.6（3.4）%。日后进行的重复测试（n = 5）显示，所有三种产品的平均可吸入分数均较高，但必可酮的可吸入分数有最高的趋势，其他两种产品的排名顺序相同。
这些体外研究结果表明，两种BDP仿制药的粒径分布与原研产品不等效。双冲击器可能未检测到粒径分布的某些差异。需要进行临床试验，以评估使用或不使用储雾罐装置的原研和仿制皮质类固醇产品的治疗等效性。
