The effects of alpha and beta anomeric ratio on the physical characteristics of anhydrous lactose raw materials and tablets

Purpose. The objective of this dissertation was to examine the effects of the alpha:beta anomeric ratio of anhydrous lactose on the physical characteristics of the raw material, on tablets made from the raw material, and on tablets containing this raw material combined with acetaminophen as a model drug.;Methods. Anhydrous beta-lactose was converted to the alpha anomer by exposure of powder to 98% relative humidity for up to four weeks in a desiccator pre-conditioned with water.;Differential scanning calorimetry and loss on drying showed that anomeric ratio could be quantitated. X-ray powder diffraction provided qualitative evidence of anomerization.;Characterization of each raw material was performed to determine any differences that may result from a change in anomeric form. Particle size and shape were assessed using microscopic methods. Evidence of morphological changes was examined using scanning electron microscopy. Surface characteristics were evaluated by surface area and porosity measurements.;The influence of anomeric changes on the structure of tablets was determined by routine tests of hardness, thickness, disintegration, and dissolution. Heckle analysis was used to determine volume reduction mechanisms during compression. Tablets containing acetaminophen as a model drug were produced for comparison.;Results. Tests performed to confirm conversion were reliable and provided qualitative and quantitative evidence of anomeric conversion. As anomeric ratios shifted toward more of the alpha anomer, particle size increased and particles became more spherical. SEM's provided evidence of morphological changes. Flow was adversely affected by increases in moisture. Surface area and porosity exhibited increases in the samples.;As moisture increased, tablet thickness increased. Tablet hardness decreased as a result of moisture and anomeric form change. Heckel analysis showed decreases in volume reduction and increases in the plastic nature as more moisture was incorporated.;Disintegration times decreased with anomeric conversion from beta to alpha. Dissolution studies showed that as the alpha anomer increased, faster dissolution rates of acetaminophen were observed.;Conclusions. Storage of anhydrous beta-lactose at high humidity for periods of time alters the alpha:beta ratio of the raw material and effects physical properties of the raw material, tablets made from the raw material, and tablets made from the raw material that also include acetaminophen as a model drug.