Chemico-calorimetric analysis of amorphous granules manufactured via continuous granulation process

Abstract

The current study explores the first case of the implementation of solution calorimetry (SolCal) in order to determine the amorphous content of crystalline benzoyl-methoxy-methylindol-acetic acid (BMA)-a model poorly soluble drug, in the amorphous granules prepared via single-step continuous twin-screw dry granulations (TSG). Amorphous magnesium aluminometasilicate (Neusilin®) (US2) was used as a novel inorganic carrier via a TwinLab 10 mm twin-screw extruder. The BMA/US2 blends were processed at 180 °C and varying drug: carrier ratios of 1:4, 1:2.5 and 1:1 (w/w). Physico-chemical characterisation conducted via SEM, DSC and XRPD showed amorphous state of the drug in all granulated formulations. Reverse optical microscopy revealed a meso-porous structure of US2 in which the drug particles are adsorbed and/or entrapped within the porous network of the carrier. This phenomenon can be the underlying reason for the increase of the amorphous content in the extruded granules. Solution calorimetry (SolCal) study revealed amorphous content of the drug in all formulations quite precisely, whereas the dynamic vapour sorption (DVS) analysis complemented the results from SolCal. Furthermore, an attempt has been made for the first time to interrelate the findings from the SolCal to that of the release of the drug from the amorphous granules. It can be concluded that SolCal can be used as a novel technique to precisely quantify and interrelate the amorphous content to its physico-chemical performances such as drug release from the granulated formulations processed via TSG.

Synergistic application of twin-screw granulation and selective laser sintering 3D printing for the development of pharmaceutical dosage forms with enhanced dissolution rates and physical properties

“…These granules demonstrated excellent flow properties, stabilized the drug in its amorphous form, and also demonstrated immediate dissolution in comparison to the crystalline drug. Indomethacin solid dispersions with inorganic excipients such as mesoporous silica have been manufactured previously using solvent evaporation techniques such as rotary evaporation, spray drying, and vacuum drying [55][56][57] where hydroxypropyl methylcellulose (HPMC) and Kollicoat® IR were used as precipitation inhibitors (PIs) combined with mesoporous silica nanoparticles (MSNs) as carriers. The present study manufactured granules with multiple mesoporous inorganic excipients, using a solvent-free, continuous process with in-line monitoring.…”

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part II

“…Considering the transitions observed in melt granulation trials, it can be concluded that twin-screw dry granulation is an effective and relatively safe process to produce quality products. Majumder et al [68] demonstrated Neusilin ® US2 as an alternative carrier in development of amorphous granules with enhanced dissolution for the model drug benzoyl-methoxy-methylindol-acetic acid (BMA) by means of a continuous dry granulation approach.…”