The effect of particle morphology on the physical stability of pharmaceutical powder mixtures
Abstract
Pharmaceutical powder mixtures are composed of particles that physically interact, precluding the formation of random mixtures. Mixtures based on particle interactions are termed ordered mixtures. The objective of this study was to determine the effect of the morphological characteristics of the components, surface texture and shape, along with size, on the formation of stable mixtures. Morphological parameters were obtained from image analysis measurements. Surface roughness was quantified using the ratio of the perimeter of the particle to that of an ideal shape (circle or square) having the same area; shape was described using the aspect ratio. The stability of mixtures of micronized aspirin with carriers of different surface roughness was determined by measuring the extent of drug adhering to the carrier after subjecting the mixtures to vibration. A lesser extent of segregation of drug from highly textured carriers relative to smoother textured carriers was observed. This was postulated to be due to a larger concentration of surface asperities on the coarser carriers which constitute potentially strong adhesion sites. The electrostatic charge on the powders was measured; differences in the response of the mixtures to the addition of magnesium stearate were attributed to electrostatic charge effects. The effect of varying the aspect ratio of the carrier and drug on segregation in polydisperse mixtures was determined from the coefficient of variation of the drug in the mixture as a function of mixing time. Reducing the size of the carrier resulted in poor homogeneity due to weak carrier-drug interactions. The variation in drug content resulting from a change in the shape of the carriers was smaller than that caused by size differences. The segregation rate constant in mixtures having dissimilarly shaped components was larger than in mixtures having components of similar shape. The effects of magnesium stearate concentration and lubrication time on the content uniformity of polydisperse mixtures were evaluated from a full factorial experiment. The segregation response of ordered and random mixtures to the addition of magnesium stearate was compared. The moisture sorption behavior of commercial magnesium stearate and the resulting morphological changes were evaluated.
Degree
Ph.D.
Advisors
Kildsig, Purdue University.
Subject Area
Pharmaceuticals|Materials science
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