Physico-Mechanical Properties of Coprocessed Excipient MicroceLac® 100 by DM(3) Approach.

ABSTRACT

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Significant MicroceLac(®)100 changes occurred with % RH exposure affecting performance attributes. HPMC physical addition did not prevent molecular or macroscopic matrix changes.