Heat assisted twin screw dry granulation

Abstract

A new “assisted” dry granulation method has been devised for the twin‐screw granulator. The method may be beneficial to drug preparation as it limits heat exposure to only one barrel zone, much shorter than melt granulation. Its mechanism was investigated using four placebo formulations, each containing a polymer binder with a glass transition temperature lower than 130°C. Variables of study included screw configuration, screw speed, barrel zone temperature, and moisture content. Granulated samples were characterized for size and porosity while feed powders were examined for their thermal transitions, interparticle friction, cohesion, and sintering rate. Results indicated that granule coalescence relied on melting of polymer binder in the kneading blocks by a combination of heat conducted from barrel and generated from screw speed friction. Successful granulation was possible with minimal addition of water, although varying the moisture content showed the relevance of the polymer's glass transition temperature and sintering progress. © 2017 American Institute of Chemical Engineers AIChE J, 2017

Analysis and Artificial Neural Network Prediction of Melting Properties and Ideal Mole fraction Solubility of Cocrystals

“…Moreover, ΔH f (T m ) is useful to set the processing parameters in the pharmaceutical industry, especially when dealing with thermodynamic processes and energetic transformations of the materials at constant pressure, 4 such as the conditions for hotmelt extrusion to avoid chemical degradation, 5,6 chemical reactions between the drug molecules and excipients, 7−10 and for conversion of pharmaceutical materials into the granules. 11,12 In the field of crystallization, the ΔH f (T m ) is useful to determine the crystalline percentage, 13 purity, and thermal stability of the material. 14−16 In addition to the ΔH f (T m ), the melting entropy is important for the understanding of the underlying reasons for CCs stability since the true stability is of course given by the free energy.…”

“…The components appear in the cocrystal in a specific stoichiometry, bonded by noncovalent interactions, especially hydrogen bonding. Cocrystals are of considerable interest to the pharmaceutical industry because of their ability to modify the physical properties of the active pharmaceutical ingredient (API), without affecting the molecular structure. − Cocrystal formation has indeed proved to be a useful tool to alter a wide range of properties including melting point, hygroscopicity, dissolution rate, thermal stability, solubility, and hence bioavailability. − For a particular API, a wide variety of molecules can be considered as coformers in the formation of a cocrystal, based on their hydrogen bonding functionalities. If the physical properties of the cocrystal could be predicted without actually having to manufacture the cocrystal, that would make the search for suitable coformers much more rapid and efficient.…”

“…Most recently, the ability to form CCs was explained on the basis of lattice energy calculations, , and in most of the cases, CCs were predicted to have a lower lattice energy by a few kcal/mol than the corresponding individual components. Moreover, Δ H f ( T m ) is useful to set the processing parameters in the pharmaceutical industry, especially when dealing with thermodynamic processes and energetic transformations of the materials at constant pressure, such as the conditions for hot-melt extrusion to avoid chemical degradation, , advancement of chemical reactions between the drug molecules and excipients, − and for conversion of pharmaceutical materials into the granules. , In the field of crystallization, the Δ H f ( T m ) is useful to determine the crystalline percentage, purity, and thermal stability of the material. − …”

Advances in Twin-Screw Granulation Processing

“…Twin screw dry granulation is considered more effective for granule manufacturing as it limits heat exposure to only one-barrel zone, much shorter than melt granulation. Lui et al (2017) studied formulations containing different polymeric binders (AF15, Kollidon VA 64 ® , Soluplus ® , Kollidon SR ® ), with glass transition temperature less than 130 °C [ 67 ]. Granulation of the primary powders with some degree of moisture was found to be beneficial for processed polymers with high glass transition temperatures.…”