Influence of particle size on the melting characteristics of organic compounds

Three bulk organic compounds of pharmaceutical interest, namely salicylic acid, benzophenone, and acetaminophen, have been analyzed by differential scanning calorimetry as a function of their particle size. For that purpose, the raw powders have been sieved in order to obtain particle size ranging from 90 to 2,000 µm. For the first time, it has been shown that the melting point of organic compounds lowers as the particle size decreases. As a matter of fact, the melting point decrease is linear with respect to the inverse of particle size and is directly related to the melting entropy of the bulk material. As far as the melting enthalpy is concerned, no change in the values has been observed in the investigated range of sizes. It is proved here that the significant depression in temperature for micrometric particles is not only directly related to the particle size decrease but also to nanosized particles adsorption on the microparticles.