Influence of Polymeric Additive on the Physical Stability and Viscoelastic Properties of Aripiprazole

Abstract

In this article, we investigated aripiprazole + Kollidon VA64 (ARP/KVA) and aripiprazole + Soluplus (ARP/SOP) amorphous solid dispersions. Thermal properties of all prepared systems have been examined by means of differential scanning calorimetry (DSC). Compositions revealing the recrystallization tendency were subsequently investigated by means of broadband dielectric spectroscopy (BDS). On the basis of dielectric data, the physically stable drug–polymer concentrations have been found. Finally, these systems have been investigated by rheology, which enables us to determine the minimal temperature required for dissolving the drug in the polymeric matrix, as well as the temperature dependence of the sample viscosity. Our investigations have shown that the amorphous form of the investigated antipsychotic drug might be effectively stabilized by both employed polymers. However, due to the better stabilization effect and the more favorable rheological properties, KVA proved to be a better polymeric excipient for extrusion of amorphous aripiprazole.

Isochronal Conditions—The Key To Maintain the Given Solubility Limit, of a Small Molecule within the Polymer Matrix, at Elevated Pressure

“…The light gray dotted spectrum is presented only as a visual aid and was not obtained during any measurement. When the recrystallization of the excess amount of the SM (FL) from the supersaturated system ceased, one well-resolved loss peak—α′-process—was still visible (as in previously reported cases 8 , 16 , 26 , 28 , 29 ), see Figure 2 c.…”

“…By utilizing Broadband Dielectric Spectroscopy (BDS) to determine the solubility limit of the SMs (e.g., drugs) dissolved within the polymer matrixes, one can additionally monitor the changes occurring in the molecular dynamics of the examined system during the whole process. 8 , 16 , 26 , 28 , 29 Furthermore, the value of the structural relaxation time (τ α ) of the measured system, which reflects its molecular mobility, 30 − 32 can be determined during dielectric measurements. As it was proven in the case of a viscous liquid, the effect of the increasing pressure on τ α is similar to the effect of the decreasing temperature.…”

High-Pressure Dielectric Studies—a Way to Experimentally Determine the Solubility of a Drug in the Polymer Matrix at Low Temperatures

“…This phenomenon has been observed for systems comprising a low- T g API and a high- T g polymer. A similar behavior was also observed during the recrystallization of flutamide in the flutamide–Kollidon VA64 system, 37 aripiprazole in compositions with Kollidon VA64 or Soluplus, 41 and sildenafil in the sildenafil + Kollidon VA64 ASD system. 43 It is worth mentioning that the opposite phenomenon, the shift of the α-relaxation process toward higher frequencies during the recrystallization corresponding to the enhancement of the plasticizing effect, can be observed in the systems based on a high- T g API and a low- T g polymer such as sildenafil + poly vinylacetate.…”

Enhancement of the Physical Stability of Amorphous Sildenafil in a Binary Mixture, with either a Plasticizing or Antiplasticizing Compound

“…During the recrystallization of the excess amount of the drug, due to the changes in concentration (decreasing amount of amorphous drug fraction), one could observe the apparent increase in the polymer concentration, which in turn affected the position of the relaxation process peak. Therefore, considering the binary systems of a drug and a polymer, this remaining process can be ascribed to either: i) segmental or secondary relaxation originating from the residual amorphous polymer, which remained after the recrystallization of the whole drug fraction from the mixture, as it was already observed in the case of other drug-polymer mixtures, ii) the primary relaxation of a different than the initial drug concentration, after the recrystallization of the excess amount of the drug from the supersaturated API-polymer mixture [4,8,47,55,74,75]. Focusing on the former, when the whole amount of the amorphous SIL recrystallizes in the binary mixture; the residual relaxation process, related to the remaining amorphous polymer, should still be visible.…”