Correlation between critical material attributes of hydroxypropyl methyl cellulose type 2910 and film coating performance
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摘要:
以2
910 型羟丙甲纤维素（HPMC）为研究目标，探究不同来源和不同型号HPMC在薄膜包衣性能方面的关键物料属性（critical material attributes，CMAs）及各CMAs与薄膜包衣相关特性间的相关关系。首先采用各种分析技术对HPMC的CMAs和薄膜包衣相关特性进行表征。其次，采用主成分分析（principal component analysis，PCA）和正交偏最小二乘判别分析(orthogonal partial least-squares discrimination analysis，OPLS-DA)对其CMAs和薄膜包衣相关特性进行系统地评估，阐明HPMC的CMAs与薄膜包衣相关特性间的内在关系。结果表明，不同厂家HPMC在黏度、重均分子量、薄膜拉伸强度、伸长率、弹性模量、溶解时间、柔韧性等方面存在明显差异。PCA和OPLS-DA分析结果表明这11个变量之间显示出一定的相关性。这两个数学模型对HPMC样本均表现出较好的区分和分类效果，OPLS-DA模型比PCA模型分类效果更好。因此，本研究对HPMC辅料自身理化性质及其成膜特性进行了全面评价，进一步采用PCA和OPLS-DA建立二者相关性，明确了不同CMAs对HPMC薄膜包衣性能的影响程度，可作为辅料生产和制剂研发中选择辅料质控项目的重要参考。-
关键词:
- 羟丙甲纤维素 /
- 成膜性能 /
- 关键物料属性 /
- 主成分分析 /
- 正交偏最小二乘判别分析
Abstract:To better promote the development of film-coated formulations and membrane agents, the present study was carried out to investigate the critical material attributes (CMAs) of different sources and models of HPMC in terms of film-coating performance and the correlation between each of the CMAs and the film-coating-related properties, using 2
910 HPMC as the research target. Firstly, various analytical techniques were used to characterize the CMAs and film coating-related properties of HPMC. Secondly, the CMAs and film coating-related properties of HPMC were systematically evaluated by principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA). The CMAs and film-coating-related properties of HPMC were systematically evaluated to elucidate the intrinsic relationship between the CMAs and film-coating-related properties of HPMC. The results showed that there were significant differences in viscosity, weight-average molecular weight, film tensile strength, elongation, elastic modulus, dissolution time, and flexibility of HPMCs from different manufacturers. The results of PCA and OPLS-DA analyses indicated that these 11 variables showed some correlations with each other. Both mathematical models showed better differentiation and classification of HPMC samples, and the OPLS-DA model had a better classification effect than the PCA model. Therefore, in this study, the physicochemical properties and the film-forming characteristic of HPMC were comprehensively evaluated, and the correlation between them was further established using PCA and OPLS-DA. The impact degree of different CMAs on the film coating performance of HPMC was clarified, which can be used as an important reference for the selection of excipient quality control programs in excipient production and formulation research and development. -
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Figure 2. Water vapor permeability measurement results of HPMC films (A) 24 h and (B) 48 h ($\bar{x}\pm {{s}} $, n=3)ns：No significant difference
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Figure 3. Elastic modulus (A), dissolution time (B), and number of folding of HPMC films (C) ($\bar{x}\pm {{s}} $, n=3)*P < 0.05, **P < 0.01, *** P < 0.001
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Figure 4. Score plot (A) and loading plot (B) of the PCA model for HPMCη: Viscosity; Mw: Weight average molecular weight; WVP: Water vapor permeance; C(-OCH3): Methoxy content; C(-OC3H7O): Hydroxypropoxy content; EM: Elastic modulus; TS: Tensile strength; E: Elongation; DT: Dissolving time; F: Flexibility
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Figure 5. Score plo (A)t, S-plot (B) and VIP indexes of the OPLS-DA model (C) for HPMC
Table 1 Methoxy and hydroxypropoxy content of HPMC of different manufacturers and type
Manufacturer Type Methoxy
content/%Hydroxypropoxy
content/%Manufacturer A E5 28.50 8.40 E50 28.60 8.90 Manufacturer B E5 29.02 8.88 E50 29.58 8.44 
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