Haware Rahul V, Kancharla Joseph P, Udupa Aishwarya K, Staton Scott, Gupta Mali R, Al-Achi Antoine, Stagner William C
College of Pharmacy & Health Sciences, Campbell University, Buies Creek, North Carolina, 27506, USA.
Pharmaceutical Education & Research Center (PERC), Campbell University, Buies Creek, North Carolina, 27506, USA.
Pharm Res. 2015 Nov;32(11):3618-35. doi: 10.1007/s11095-015-1721-3. Epub 2015 Jun 9.
To determine the effect of relative humidity (RH) and hydroxypropyl methylcellulose (HPMC) on the physico-mechanical properties of coprocessed MacroceLac(®) 100 using 'DM(3)' approach.
Effects of RH and 5% w/w HPMC on MacroceLac(®) 100 Compressibility Index (CI) and tablet mechanical strength (TMS) were evaluated by 'DM(3)'. The 'DM(3)' approach evaluates material properties by combining 'design of experiments', material's 'macroscopic' properties, 'molecular' properties, and 'multivariate analysis' tools. A 4X4 full-factorial experimental design was used to study the relationship of MacroceLac(®) 100 molecular properties (moisture content, dehydration, crystallization, fusion enthalpy, and moisture uptake) and macroscopic particle size and shape on CI and TMS. A physical binary mixture (PBM) of similar composition to MacroceLac(®) 100 was also evaluated. Multivariate analysis of variance (MANOVA), principle component analysis, and partial least squares (PLS) were used to analyze the data.
MANOVA CI ranking was: PBM-HPMC > PBM > MicroceLac(®)100 > MicroceLac(®)100-HPMC (p < 0.0001). MANOVA showed PBM's and PBM-HPMC's TMS values were lower than MicroceLac(®)100 and MicroceLac(®)100-HPMC (p < 0.0001). PLS showed that % RH, HPMC, and several molecular properties significantly affected CI and TMS.
Significant MicroceLac(®)100 changes occurred with % RH exposure affecting performance attributes. HPMC physical addition did not prevent molecular or macroscopic matrix changes.
采用“DM(3)”方法确定相对湿度（RH）和羟丙基甲基纤维素（HPMC）对共处理的MacroceLac(®) 100物理机械性能的影响。
通过“DM(3)”评估RH和5% w/w HPMC对MacroceLac(®) 100可压性指数（CI）和片剂机械强度（TMS）的影响。“DM(3)”方法通过结合“实验设计”、材料的“宏观”性能、“分子”性能和“多变量分析”工具来评估材料性能。采用4×4全因子实验设计研究MacroceLac(®) 100分子性能（水分含量、脱水、结晶、熔融焓和吸湿）以及宏观粒度和形状与CI和TMS之间的关系。还评估了与MacroceLac(®) 100组成相似的物理二元混合物（PBM）。使用多变量方差分析（MANOVA）、主成分分析和偏最小二乘法（PLS）对数据进行分析。
MANOVA对CI的排序为：PBM-HPMC > PBM > MicroceLac(®)100 > MicroceLac(®)100-HPMC（p < 0.0001）。MANOVA显示PBM和PBM-HPMC的TMS值低于MicroceLac(®)100和MicroceLac(®)100-HPMC（p < 0.0001）。PLS表明，RH百分比、HPMC和几个分子性能对CI和TMS有显著影响。
MacroceLac(®) 100随RH暴露百分比发生显著变化，影响性能属性。HPMC的物理添加并不能阻止分子或宏观基质的变化。
