Objective:To establish a laser light diffraction method for determination of the particle size and particle size distribution of bromhexine hydrochloride, and to explore the effect of the particle size of active pharmaceutical ingredient (API) on the dissolution in vitro. Methods:The Malvern Mastersizer 3000 laser particle size analyzer with AERO S dry sampler was used. The determination conditions were as follows:background measurement time:10 s, sample measurement time:15 s, obscuration:0.50%-5%, particle RI∶1.626, particle AI∶0.1, analysis model:general, fine dry powder model, pressure:350 kPa, sampling velocity:40%, hopper gap:2.0 mm, sample weight:200 mg. Results:The laser diffraction method could be used to determine the particle size of bromhexine hydrochloride. The relative standard deviation values (RSD%) of methodology validation and sample measurement were less than 5%. The particle size distribution values of 4 batches of self-made samples were 30.05, 40.60, 48.60 and 82.20 μm, respectively. The larger the particle size of the API, the slower the dissolution rate of the granules. Conclusion:The method is suitable for the particle size and its distribution determination of bromhexine hydrochloride. And the particle size distribution of bromhexine hydrochloride has significant influence on the release of granules, therefore it is very important to control the particle size in the production process of pharmaceutical preparation.
WANG Yue, WU Song, XUE Dan, ZHANG Kun, SHAO Hui-hui, XU Wei-guo, ZHANG Dui-liang, ZHANG Song, YANG Qing-yun
. Methodological study of particle size distribution of bromhexine hydrochloride by laser diffraction method*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(8)
: 1448
-1453
.
DOI: 10.16155/j.0254-1793.2021.08.20
[1] MAGGIO R,CORSINI GU.Repurposing the mucolytic cough suppressant and TMPRSS2 protease inhibitor bromhexine for the prevention and management of SARS-CoV-2 infection[J].Pharm Res,2020,157(157):1
[2] LUCAS JM,HEINLEIN C,KIM T,et al.The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis[J].Cancer Discov,2014,4(11):1310
[3] SHEN LW,MAO HJ,WU YL,et al.TMPRSS2:A potential target for treatment of influenza virus and coronavirus infections[J]. Biochimie,2017,142(142):1
[4] ANSARIN K,TOLOUIAN R,ARDALAN M,et al.Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients:a randomized clinical trial[J].BioImpacts,2020,10(4): 209
[5] 中华人民共和国药典2020 年版. 二部[S].2020:1325
ChP 2020. VolⅡ[S].2020:1325
[6] SUN J,WANG F,SUI Y,et al.Effect of particle size on solubility, dissolution rate,and oral bioavailability:evaluation using coenzyme Q10 as naked nanocrystals[J].Int J Nanomedicine,2012(7): 5733
[7] KUCHENBECKER P,GEMEINERT M,RABE T.Inter-laboratory study of particle size distribution measurements by laser diffraction[J].Part Part Syst Charact,2012,29(4):304
[8] 丁怡. 激光散射法测定酪酸梭菌肠球菌三联活菌散粒度的探讨[J].中国药师,2017,20(4):757
DING Y.Determination of particle size of clostridium butyricum enterococcus triple viable powder by laser light scattering method[J].China Pharm,2017,20(4):757
[9] 丁怡,方海顺.激光粒度散射法测定微晶纤维素粒度的研究与应用[J].今日药学,2017,27(4):237
DING Y,FANG HS.Study and application of particle size of microcrystalline cellulose by laser scattering analyzer[J].Pharm Today,2017,27(4):237
[10] SASSIKOVA M,MARSALEK R.Characterization of the size distribution of subbituminous coal by laser diffraction[J].Instrum Sci Technol,2016,44(3):233
[11] 沈丹丹,曾令高,许娟,等.激光粒度仪测定环索奈德粒度分布的应用研究[J].中国抗生素杂志,2019,44(8):946
SHEN DD,ZENG GL,XU J,et al.Application of the laser particle analyzer to determine the laser particle size of ciclesonide[J].Chin J Antibiot,2019,44(8):946
[12] 吴燕,刘菁,安彦,等.甲基纤维素粒度与粒度分布测定法研究[J].药物分析杂志,2019,39(4):755
WU Y,LIU J,AN Y,et al.Methodological study on particle size distribution of methylcellulose by laser particle analyzer[J].Chin J Pharm Anal,2019,39(4):755
[13] GB/T 19077 – 2016 粒度分析激光衍射法[S]. 2016:11
GB/T 19077 – 2016 Particle Size Analysis – Laser Diffraction Methods[S]. 2016:11
[14] CHU KR,LEE E,JEONG SH,et al.Effect of particle size on the dissolution behaviors of poorly water-soluble drugs[J].Archives Pharm Res,2012,35(7):1187
[15] 关玉晶,杨波,蒋翠莺.光散射法测定难溶性药物粒度[J].海峡药学,2017,29(7):1
GUAN YJ,YANG B,JIANG CY.Determination of particle size distribution of poorly water-soluble drugs by laser light diffraction technique[J].Strait Pharm J,2017,29(7):1
[16] 郝福,胡向青,巴晓雨,等.激光粒度分析技术在药物研究和质量控制中的应用进展[J].分析测试技术与仪器,2017,23(2):72
HAO F,HU XQ,BA XY,et al.Advances of application of laser diffraction technique of particle size analysis in pharmaceutical quality analysis[J].Anal Testing Technol Instrum,2017,23(2):72