A Mechanistic Investigation of An Amorphous Pharmaceutical and Its Solid Dispersions, Part II: Molecular Mobility and Activation Thermodynamic Parameters

Abstract

Using thermal windowing, a distribution of temperature-dependent relaxation times encountered in real systems was obtained as opposed to a single average value routinely acquired by other techniques. Relevant kinetic parameters were obtained and used in mechanistically delineating the effects on molecular mobility of temperature and incorporating the drug in a polymer. This allows for appropriate choices to be made regarding drug loading, storage temperature, and type of polymer that would realistically correlate to physical stability.

Local Mobility in Amorphous Pharmaceuticals—Characterization and Implications on Stability

“…It has been successfully used to characterize amorphous pharmaceuticals and is particularly useful to investigate molecular mobility in the amorphous phase. 10,16,87,88,[108][109][110][111][112] One of the TSC techniques, TSDC or thermally stimulated depolarization current consists of applying an electric field to the sample at a particular temperature causing dipolar reorientation. This is followed by quenching the sample to ''freeze'' the dipolar orientations and subsequently measuring the depolarization current during heating as a measure of molecular mobility.…”

“…TSDC can serve as a great complementary tool to DRS in that DRS can be conveniently used to study mobility above the T g whereas TSDC is suited to examine mobility below the T g as demonstrated by Alie et al 16 The fractional polarization technique of TSDC could be especially used to derive information about narrow populations of relaxing species by selective activation of dipoles. 112 The other related, less frequently used technique is the thermally stimulated polarization current (TSPC) which consists of application of an electric field at a low temperature where dipole mobility is restricted, followed by polarization of the dipoles during heating. 113 Compared to TSDC, TSPC has the advantage of probing a material with minimal effect on its thermal history and has been used to characterize local motions in pharmaceutical macromolecules.…”

Characterisation and Prediction of Phase Separation in Hot-Melt Extruded Solid Dispersions: A Thermal, Microscopic and NMR Relaxometry Study

“…More specifically, a significant improvement in the dissolution rate of drugs may be elicited by the formation of a solid dispersion via the hot-melt extrusion process, thereby potentially eliciting an improvement in bioavailability for BCS class II and IV drugs (2,7,8). While the solid dispersions may manifest as a range of binary systems, the formation of a solid solution of the drug within the polymer is generally regarded as being desirable mainly for reason of in vitro drug release performance (6,(9)(10)(11)(12)(13). In the case of HME, the processing involves dispersion and fusion under mechanical stress.…”

Soluble Itraconazole in Tablet Form Using Disordered Drug Delivery Approach: Critical Scale-up Considerations and Bio-equivalence Studies

“…In-depth solid-state characterization of developed formulation at three critically important stages, namely formation of glass system, coating of glass system onto pellets and compression of crushed pellets into tablets, further helped in better understanding of mechanistic approach involved in ITZ solubilization and stabilization (21)(22)(23)(24)26). DSC is an important test for molecular embedment of drugs inside polymer matrix.…”