Karolina Adrjanowicz, Marian Paluch

Mielenie jako alternatywna metoda otrzymywania substancji leczniczych w formie amorficznej

Milling – an alternative method of Active Pharmaceutical Ingredients (APIs) amorphization

Milling is a very popular technique applied in many fields of industry to reduce particle size. The large amount of mechanical perturbation generated during milling may result in significant changes in the structure of outcome material, including polymorphic transformation, crystal defects, partial or complete amorphization.
Amorphous Active Pharmaceutical Ingredients (APIs) are very promising perspective for pharmaceutical industry, mainly because of grater solubility, higher dissolution rate and improvement of bioavailability compare to theirs crystalline counterparts. Moreover, sometimes they even compact into tablets much better than crystalline powder, which is very important from production, technical and economical consideration.
As reported many times in the literature, transformation crystalline – amorphous material induced by mechanical treatment is more effective when milling process takes place at temperature much lower than the glass transition temperature Tg. In recent years new milling technique, so called cryomilling, has become considerable more interesting than conventional ball-milling. Cryomilling (or alternatively cryogenic grinding) is a high-impact process which takes place at liquid nitrogen temperature. In contrast to traditional ambient temperature device, in cryogenic equipment we are able to obtain totally amorphous pharmaceuticals within much shorter milling time. As believed, cryogenic temperature should also minimalize the energy expenditure and produce amorphous materials without thermal degradation.
Keywords: amorphous pharmaceuticals, glass transition temperature, cryogenic grinding, solid state amorphization.