Abstract：OBJECTIVE To put forward considerations for the quality evaluation of solid dispersions prepared by hot melt extrusion (HME) from the perspectives of formulation, production process and quality control, and provide reference for pharmaceutical development. METHODS The solid dispersion preparations which have been marketed in recent years were summarized, and the types and functions of key excipients were discussed. The formulation and production process of HME were introduce, and the basic considerations for the quality control of solid dispersions were put forward. RESULTS The types of excipients commonly used in the formulation of HME solid dispersions included carrier matrixes, plasticizers, surfactants, and glidants. The carrier matrixes used in marketed formulations mainly include PVP/VA, HPMCAS, and HPMC. Hot melt extrusion temperature and screw kneading are the key process parameters that affect the quality of solid dispersions. Quality control should focus on amorphous and dissolution. CONCLUSION It is important to pay attention to the change of quality of solid dispersions under long-term and accelerated storage conditions, especially for amorphous and dissolution.
马骏威, 安娜. 热熔挤出法固体分散体质量评价的考虑[J]. 中国药学杂志, 2020, 55(21): 1819-1823.
MA Jun-wei, AN Na. Consideration for Quality Evaluation of Solid Dispersions Prepared by Hot Melt Extrusion. Chinese Pharmaceutical Journal, 2020, 55(21): 1819-1823.
CUI D F. Pharmaceutics(药剂学) [M]. Beijing: People′s Medical Publishing House, 2011: 347-354.
[2]
HAN F, ZHANG W, WANG Y, et al. Applying supercritical fluid technology to prepare ibuprofen solid dispersions with improved oral bioavailability[J]. Pharmaceutics, 2019, 11(2):67-80.
[3]
LAFOUNTAINE J S, JERMAIN S V, PRASAD L K, et al. Enabling thermal processing of ritonavir-polyvinyl alcohol amorphous solid dispersions by KinetiSol® dispersing[J]. Eur J Pharm Biopharm, 2016, 101: 72-81.
[4]
HUANG Y, DAI W G. Fundamental aspects of solid dispersion technology for poorly soluble drugs[J]. Acta Pharm Sin B(药学学报 英文), 2014, 4(1):18-25.
[5]
MCKELVEY C A, KESISOGLOU F. Enabling an HCV treatment revolution and the frontiers of solid solution formulation[J]. J Pharm Sci, 2019, 108(1):50-57.
[6]
HUANG S, WILLIAMS R O. Effects of the preparation process on the properties of amorphous solid dispersions[J]. AAPS Pharm Sci Technol, 2018, 19(5):1971-1984.
[7]
RAHMAN M, OZKAN S, LESTER J, et al. Annual Meeting of the American Association of Pharmaceutical Scientists: Plasticizer Compatibility and Thermal and Rheological Properties of PlasdoneTM povidone And copovidone polymers for Hot-melt Extrusion Applications[C]. Chicago: Ashland, 2012:1-7.
[8]
ALBERS J. Hot-Melt Extrusion With Poorly Soluble Drugs[M]. Göttingen: Cuvillier, 2008.
[9]
SOLANKI N G, GUMASTE S G, SHAH A V, et al. Effects of surfactants on itraconazole-hydroxypropyl methylcellulose acetate succinate solid dispersion prepared by hot melt extrusion. Ⅱ: rheological analysis and extrudability testing[J]. J Pharm Sci, 2019, 108(9):3063-3073.
[10]
KEEN J M, MCGINITY J W. Melt Extruded Controlled Release Dosage Forms[M]. New York:Springer, 2013: 243-260.
[11]
NAKAMICHI K, NAKANO T, YASUURA H, et al. The role of the kneading paddle and the effects of screw revolution speed and water content on the preparation of solid dispersions using a twin-screw extruder[J]. Int J Pharm, 2002, 241(2):203-211.
[12]
HUANG R, YE X X, LU D, et al. Analysis of the polymorphism of furosemide by Raman spectroscopy and establishment of the quantitative model [J]. Chin Pharma J(中国药学杂志),2018, 53(24):2127-2131.
[13]
NEWMAN A, HASTEDT J E, YAZDANIAN M. New directions in pharmaceutical amorphous materials and amorphous solid dispersions, a tribute to Professor George Zografi-Proceedings of the June 2016 Land O′Lakes Conference[J]. AAPS Open, 2017, 3(1):7-19.
[14]
LAGGNER P, PAUDEL A. Density fluctuations in amorphous pharmaceutical solids. Can SAXS help to predict stability?[J]. Colloids Surf B Biointerfaces, 2018, 168: 76-82.
[15]
PICCINNI P, TIAN Y, MCNAUGHTON A, et al. Solubility parameter-based screening methods for early-stage formulation development of itraconazole amorphous solid dispersions[J]. J Pharm Pharmacol, 2016, 68(5):705-720.
[16]
IBRAHIM M, ZHANG J, REPKA M, et al. Characterization of the solid physical state of API and its distribution in pharmaceutical hot melt extrudates using Terahertz Raman imaging[J]. Aaps Pharmscitech, 2019, 20(2):62-70.
[17]
CRAIG D Q M. The mechanisms of drug release from solid dispersions in water-soluble polymers[J]. Int J Pharm, 2002, 231(2):131-144.
[18]
SABOO S, MUGHEIRBI N A, ZEMLYANOV D Y, et al. Congruent release of drug and polymer: a “sweet spot” in the dissolution of amorphous solid dispersions[J]. J Controlled Release, 2019, 298(1):68-82.
[19]
KAKUMANU V K, BANSAL A K. Enthalpy relaxation studies of celecoxib amorphous mixtures[J]. Pharm Res, 2002, 19(12):1873-1878.
[20]
ZHOU D, ZHANG G G Z, LAW D, et al. Physical stability of amorphous pharmaceuticals: importance of configurational thermodynamic quantities and molecular mobility[J]. J Pharm Sci, 2002, 91(8):1863-1872.
[21]
SUN M, WU C, FU Q, et al. Solvent-shift strategy to identify suitable polymers to inhibit humidity-induced solid-state crystallization of lacidipine amorphous solid dispersions[J]. Int J Pharm, 2016, 503(1-2):238-246.
[22]
WU Q, KENNEDY M T, NAGAPUDI K, et al. Humidity induced phase transformation of poloxamer 188 and its effect on physical stability of amorphous solid dispersion of AMG 579, a PDE10A inhibitor[J]. Int J Pharm, 2017, 521(1-2):1-7.
[23]
DESHMUKH S, PARADKAR A, ABRAHMSÉN-ALAMI S, et al. Injection moulded controlled release amorphous solid dispersions: synchronized drug and polymer release for robust performance[J]. Int J Pharm, 2020, 575(19):118908-118950.
[24]
SARODE A L, OBARA S, TANNO F K, et al. Stability assessment of hypromellose acetate succinate (HPMCAS) NF for application in hot melt extrusion (HME)[J]. Carbohydr Polym, 2014, 101(9):146-153.
2020, Vol. 55 
