ABSTRACT
This study quantifies the lubricating efficiency of two grades of crystalline vegetable-derived magnesium stearate (MgSt-V) using the DM(3) approach, which utilizes design of experiments (D) and multivariate analysis techniques (M3) to evaluate the effect of a material's (M1) molecular and macroscopic properties and manufacturing factors (M2) on critical product attributes. A 2(3) factorial design (2 continuous variables plus 1 categorical factor) with three center points for each categorical factor was used to evaluate the effect of MgSt-V fraction and blend time on running powder basic flow energy (BFE), tablet mechanical strength (TMS), disintegration time (DT), and running powder lubricant sensitivity ratio (LSR). Molecular characterization of MgSt-V employed moisture sorption-desorption analysis, (13)C nuclear magnetic resonance spectroscopy, thermal analysis, and powder X-ray diffraction. MgSt-V macroscopic analysis included mean particle size, specific surface area, particle morphology, and BFE. Principal component analysis and partial least squares multivariate analysis techniques were used to develop predictive qualitative and quantitative relationships between the molecular and macroscopic properties of MgSt-V grades, design variables, and resulting tablet formulation properties. MgSt-V fraction and blending time and their square effects showed statistical significant effects. Significant variation in the molecular and macroscopic properties of MgSt-V did not have a statistically significant impact on the studied product quality attributes (BFE, TMS, DT, and LSR). In setting excipient release specifications, functional testing may be appropriate in certain cases to assess the effect of statistically significant different molecular and macroscopic properties on product quality attributes.
Subject(s)
Stearic Acids/chemistry , Vegetables/chemistry , Chemistry, Pharmaceutical/methods , Excipients/chemistry , Lubricants/chemistry , Lubrication/methods , Particle Size , Powders/chemistry , Tablets/chemistry , X-Ray Diffraction/methodsABSTRACT
This work distinguishes and quantifies the effects of bovine- and vegetable-derived magnesium stearate (MgSt) molecular and macroscopic properties on lubrication efficiency using multivariate analysis. Principal component analysis (PCA) and partial least-square regression (PLS) were used to evaluate and quantify the lubricant effectiveness on a model tablet formulation. PCA score and loading plots showed a separation of model formulations based on the MgSt sources, which indicated different bovine- and vegetable-derived MgSt lubrication potential. PLS quantified the MgSt molecular [enthalpy of dehydration (ΔHd), enthalpy of melting (ΔHm), percent crystallinity, and moisture content] and macroscopic [particle size (d50 ), specific surface area (SSA-MgSt), and MgSt Hausner ratio (HF-MgSt)] properties, their interactions, and square effects on formulation powder flow and tableting properties relating to MgSt's lubrication effectiveness. For crystalline MgSt, moisture content, HF-MgSt, d50 , and SSA-MgSt showed a major influence on the lubrication efficiency compared with the other MgSt molecular properties (percent crystallinity, ΔHm, and ΔHd). Amorphous MgSt showed poor lubrication, and none of its molecular or macroscopic properties showed significant effects on lubrication efficiency.
