Miscibility of amorphous solid dispersions: A rheological and solid-state NMR spectroscopy study.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Amorphous solid dispersions (ASDs) are crucial for drug stability, but predicting their crystallization resistance requires accurate miscibility assessment.
• Current methods for determining miscibility in ASDs face theoretical and practical limitations, especially concerning temperature dependence.

Purpose of the Study:

• To compare the miscibility of nifedipine/polyvinylpyrrolidone (NIF/PVP) ASDs using a high-temperature rheological approach and low-temperature solid-state Nuclear Magnetic Resonance (ssNMR).
• To evaluate the applicability of the polymer overlap concentration (c*) based rheological method for inferring ASD miscibility at temperatures significantly below the glass transition temperature (T_g).

Main Methods:

• Utilized a rheological approach based on polymer overlap concentration (c*) at 175°C (above NIF's melting temperature, T_m).
• Employed solid-state NMR (ssNMR) ¹H T₁ and T_1ρ relaxation times at -20°C (below NIF/PVP's T_g) to assess miscibility.
• Compared NIF/PVP ASDs with varying polyvinylpyrrolidone (PVP) molecular weights (M_w).

Main Results:

• The rheological approach at high temperatures showed good agreement with ssNMR measurements at low temperatures.
• For low M_w PVP, ssNMR ¹H T_1ρ relaxation times correlated better with the rheological findings.
• For high M_w PVP, ssNMR ¹H T₁ relaxation times were more consistent with the rheological approach.

Conclusions:

• The c* based rheological approach is a valuable tool for predicting the miscibility of ASDs even at deeply cooled states.
• Findings support the use of rheology for inferring long-term physical stability of ASDs across a wide temperature range.
• This study bridges the gap in understanding temperature-dependent miscibility in ASDs.