The purpose of the present study was to determine how environmental factors affected the crystallization of amorphous maltose, determine how those factors affected the post compaction hardening of oral fast dissolve tablets containing amorphous maltose, and to determine the crystallization kinetics and activation energy of amorphous maltose crystallization and separate out the activation energy of nucleation of amorphous maltose. The environmental factors temperature, humidity, time, crystalline seed concentration and milling of crystalline seeds all had a significant effect on the crystallization of amorphous maltose. Humidity had the greatest effect and dominated over the presence of non-milled or milled seeds. The post compaction hardening of oral fast dissolve tablets containing amorphous maltose was found to increase with initial crystallization of amorphous maltose while porosity data on the granulation shows a general decline in both the surface area and cumulative pore volume of micropores. The rate of crystallization of amorphous maltose followed a path characteristic of a transformation controlled by nucleation followed by crystal growth. The Avrami-Erofe'ev equation was chosen to calculate the crystallization kinetics of amorphous maltose. The rate of crystallization of amorphous maltose, treated with 70% relative humidity, increased with increasing temperature. The activation energy for amorphous maltose crystallization was determined from Arrhenious plots of ln k versus 1/T. The value for the isothermal activation energy of amorphous maltose crystallization was found to be 106.6 kJ/mol, which is of the same order of magnitude as that reported for amorphous lactose crystallization of 187 kJ/mol. The kinetics of nucleation was determined by analyzing only the initial time points of amorphous maltose: crystallization. The value for the activation energy for the nucleation of amorphous maltose was found to be 131 kJ/mol. This value was lower than that reported for amorphous lactose by a factor of two, which can be attributed to the difference in environmental conditions seen between the two studies. The determination of activation energy for nucleation leads to a better understanding of the crystallization process and therefore allows for a better understanding of the effect of excipients, added to the formulation of orally disintegrating tablets, on the crystallization process.
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