Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz

Research output: Contribution to journalJournal articlepeer-review

Standard

Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz. / Jørgensen, Jacob Rune; Mohr, Wolfgang; Rischer, Matthias; Sauer, Andreas; Mistry, Shilpa; Müllertz, Anette; Rades, Thomas.

In: International Journal of Pharmaceutics, Vol. 632, 122564, 2023.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Jørgensen, JR, Mohr, W, Rischer, M, Sauer, A, Mistry, S, Müllertz, A & Rades, T 2023, 'Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz', International Journal of Pharmaceutics, vol. 632, 122564. https://doi.org/10.1016/j.ijpharm.2022.122564

APA

Jørgensen, J. R., Mohr, W., Rischer, M., Sauer, A., Mistry, S., Müllertz, A., & Rades, T. (2023). Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz. International Journal of Pharmaceutics, 632, [122564]. https://doi.org/10.1016/j.ijpharm.2022.122564

Vancouver

Jørgensen JR, Mohr W, Rischer M, Sauer A, Mistry S, Müllertz A et al. Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz. International Journal of Pharmaceutics. 2023;632. 122564. https://doi.org/10.1016/j.ijpharm.2022.122564

Author

Jørgensen, Jacob Rune ; Mohr, Wolfgang ; Rischer, Matthias ; Sauer, Andreas ; Mistry, Shilpa ; Müllertz, Anette ; Rades, Thomas. / Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz. In: International Journal of Pharmaceutics. 2023 ; Vol. 632.

Bibtex

@article{53f84acc217a4effb3c96e0b93f2b578,
title = "Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz",
abstract = "In this study, the stability and intrinsic dissolution of vacuum compression molded (VCM) amorphous solid dispersions (ASDs) of efavirenz (EFV) were investigated in relation to its solubility limits in seven polymers determined by the melting point depression (MPD) method. The extrapolated solubility limits of EFV at 22 °C ranged from 3 to 68% (w/w) with PVOH being the only polymer suggesting immiscibility with EFV according to both MPD and Hansen solubility parameters (HSPs). All ASDs with EFV loadings below or close to their calculated solubility limit did not show any signs of crystallization upon conditioning for 7 months at either 22 or 37 °C and 23 or 75% relative humidity. However, all ASDs with EFV loading above the solubility limit crystallized at high humidity, while the ASDs with cellulose derived carrier polymers proved kinetically stable at low humidity over 7 months. While the EFV intrinsic dissolution rates from the VCM ASDs were partly depending on the polymer dissolution rate, no correlation was observed between EFV matrix crystallization and its miscibility in the polymer. Altogether, the observations of the study underline the importance of combining preformulation miscibility determination and dissolution studies to rationally decide on both stability and viability of ASD formulations.",
keywords = "Differential scanning calorimetry, Flory-Huggins, Hansen solubility parameters, Polarized light microscopy, X-ray diffraction",
author = "J{\o}rgensen, {Jacob Rune} and Wolfgang Mohr and Matthias Rischer and Andreas Sauer and Shilpa Mistry and Anette M{\"u}llertz and Thomas Rades",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
doi = "10.1016/j.ijpharm.2022.122564",
language = "English",
volume = "632",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz

AU - Jørgensen, Jacob Rune

AU - Mohr, Wolfgang

AU - Rischer, Matthias

AU - Sauer, Andreas

AU - Mistry, Shilpa

AU - Müllertz, Anette

AU - Rades, Thomas

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - In this study, the stability and intrinsic dissolution of vacuum compression molded (VCM) amorphous solid dispersions (ASDs) of efavirenz (EFV) were investigated in relation to its solubility limits in seven polymers determined by the melting point depression (MPD) method. The extrapolated solubility limits of EFV at 22 °C ranged from 3 to 68% (w/w) with PVOH being the only polymer suggesting immiscibility with EFV according to both MPD and Hansen solubility parameters (HSPs). All ASDs with EFV loadings below or close to their calculated solubility limit did not show any signs of crystallization upon conditioning for 7 months at either 22 or 37 °C and 23 or 75% relative humidity. However, all ASDs with EFV loading above the solubility limit crystallized at high humidity, while the ASDs with cellulose derived carrier polymers proved kinetically stable at low humidity over 7 months. While the EFV intrinsic dissolution rates from the VCM ASDs were partly depending on the polymer dissolution rate, no correlation was observed between EFV matrix crystallization and its miscibility in the polymer. Altogether, the observations of the study underline the importance of combining preformulation miscibility determination and dissolution studies to rationally decide on both stability and viability of ASD formulations.

AB - In this study, the stability and intrinsic dissolution of vacuum compression molded (VCM) amorphous solid dispersions (ASDs) of efavirenz (EFV) were investigated in relation to its solubility limits in seven polymers determined by the melting point depression (MPD) method. The extrapolated solubility limits of EFV at 22 °C ranged from 3 to 68% (w/w) with PVOH being the only polymer suggesting immiscibility with EFV according to both MPD and Hansen solubility parameters (HSPs). All ASDs with EFV loadings below or close to their calculated solubility limit did not show any signs of crystallization upon conditioning for 7 months at either 22 or 37 °C and 23 or 75% relative humidity. However, all ASDs with EFV loading above the solubility limit crystallized at high humidity, while the ASDs with cellulose derived carrier polymers proved kinetically stable at low humidity over 7 months. While the EFV intrinsic dissolution rates from the VCM ASDs were partly depending on the polymer dissolution rate, no correlation was observed between EFV matrix crystallization and its miscibility in the polymer. Altogether, the observations of the study underline the importance of combining preformulation miscibility determination and dissolution studies to rationally decide on both stability and viability of ASD formulations.

KW - Differential scanning calorimetry

KW - Flory-Huggins

KW - Hansen solubility parameters

KW - Polarized light microscopy

KW - X-ray diffraction

U2 - 10.1016/j.ijpharm.2022.122564

DO - 10.1016/j.ijpharm.2022.122564

M3 - Journal article

C2 - 36586638

AN - SCOPUS:85146033043

VL - 632

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 122564

ER -

ID: 333701902