Tags

Type your tag names separated by a space and hit enter

Influence of Low-Molecular-Weight Excipients on the Phase Behavior of PVPVA64 Amorphous Solid Dispersions.
Pharm Res. 2018 01 05; 35(1):25.PR

Abstract

PURPOSE

The oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs) can be improved by the preparation of amorphous solid dispersions (ASDs) where the API is dissolved in polymeric excipients. Desired properties of such ASDs like storage stability, dissolution behavior, and processability can be optimized by additional excipients. In this work, the influence of so-called low-molecular-weight excipients (LMWEs) on the phase behavior of ASDs was investigated.

METHOD

Binary ASDs of an amorphous API, naproxen (NAP) or acetaminophen (APAP), embedded in poly-(vinylpyrrolidone-co-vinyl acetate) (PVPVA64) were chosen as reference systems. Polyethylene glycol 1500 (PEG1500), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS1000), propylene glycol monocaprylate type II (Capryol™ 90), and propylene glycol monolaurate type I (Lauroglycol™ FCC) were used as LMWEs. The API solubility in the excipients and the glass-transition temperature of the ASDs were modeled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) and the Kwei equation, respectively, and compared to corresponding experimental data.

RESULTS

The API solubility curves in ternary systems with 90/10 wt%/wt% PVPVA64/LMWE ratios were very close to those in pure PVPVA64. However, the glass-transition temperatures of API/PVPVA64/LMWE ASDs were much lower than those of API/PVPVA64 ASDs. These effects were determined experimentally and agreed with the predictions using the PC-SAFT and Kwei models.

CONCLUSION

The impact of the LMWEs on the thermodynamic stability of the ASDs is quite small while the kinetic stability is significantly decreased even by small LMWE amounts. PC-SAFT and the Kwei equation are suitable tools for predicting the influence of LMWEs on the ASD phase behavior.

Authors+Show Affiliations

Global Pharmaceutical R&D, AbbVie Deutschland GmbH & Co. KG, Knollstraβe, D-67061, Ludwigshafen am Rhein, Germany. Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, TU Dortmund, Emil-Figge-Str. 70, D-44227, Dortmund, Germany.Global Pharmaceutical R&D, AbbVie Deutschland GmbH & Co. KG, Knollstraβe, D-67061, Ludwigshafen am Rhein, Germany. samuel.kyeremateng@abbvie.com.Global Pharmaceutical R&D, AbbVie Deutschland GmbH & Co. KG, Knollstraβe, D-67061, Ludwigshafen am Rhein, Germany.Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, TU Dortmund, Emil-Figge-Str. 70, D-44227, Dortmund, Germany. gabriele.sadowski@tu-dortmund.de.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29305717

Citation

Lehmkemper, Kristin, et al. "Influence of Low-Molecular-Weight Excipients On the Phase Behavior of PVPVA64 Amorphous Solid Dispersions." Pharmaceutical Research, vol. 35, no. 1, 2018, p. 25.
Lehmkemper K, Kyeremateng SO, Degenhardt M, et al. Influence of Low-Molecular-Weight Excipients on the Phase Behavior of PVPVA64 Amorphous Solid Dispersions. Pharm Res. 2018;35(1):25.
Lehmkemper, K., Kyeremateng, S. O., Degenhardt, M., & Sadowski, G. (2018). Influence of Low-Molecular-Weight Excipients on the Phase Behavior of PVPVA64 Amorphous Solid Dispersions. Pharmaceutical Research, 35(1), 25. https://doi.org/10.1007/s11095-017-2316-y
Lehmkemper K, et al. Influence of Low-Molecular-Weight Excipients On the Phase Behavior of PVPVA64 Amorphous Solid Dispersions. Pharm Res. 2018 01 5;35(1):25. PubMed PMID: 29305717.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of Low-Molecular-Weight Excipients on the Phase Behavior of PVPVA64 Amorphous Solid Dispersions. AU - Lehmkemper,Kristin, AU - Kyeremateng,Samuel O, AU - Degenhardt,Matthias, AU - Sadowski,Gabriele, Y1 - 2018/01/05/ PY - 2017/09/13/received PY - 2017/11/19/accepted PY - 2018/1/7/entrez PY - 2018/1/7/pubmed PY - 2018/11/13/medline KW - amorphous solid dispersion, PC-SAFT, phase behavior, surfactants, thermodynamic model SP - 25 EP - 25 JF - Pharmaceutical research JO - Pharm Res VL - 35 IS - 1 N2 - PURPOSE: The oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs) can be improved by the preparation of amorphous solid dispersions (ASDs) where the API is dissolved in polymeric excipients. Desired properties of such ASDs like storage stability, dissolution behavior, and processability can be optimized by additional excipients. In this work, the influence of so-called low-molecular-weight excipients (LMWEs) on the phase behavior of ASDs was investigated. METHOD: Binary ASDs of an amorphous API, naproxen (NAP) or acetaminophen (APAP), embedded in poly-(vinylpyrrolidone-co-vinyl acetate) (PVPVA64) were chosen as reference systems. Polyethylene glycol 1500 (PEG1500), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS1000), propylene glycol monocaprylate type II (Capryol™ 90), and propylene glycol monolaurate type I (Lauroglycol™ FCC) were used as LMWEs. The API solubility in the excipients and the glass-transition temperature of the ASDs were modeled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) and the Kwei equation, respectively, and compared to corresponding experimental data. RESULTS: The API solubility curves in ternary systems with 90/10 wt%/wt% PVPVA64/LMWE ratios were very close to those in pure PVPVA64. However, the glass-transition temperatures of API/PVPVA64/LMWE ASDs were much lower than those of API/PVPVA64 ASDs. These effects were determined experimentally and agreed with the predictions using the PC-SAFT and Kwei models. CONCLUSION: The impact of the LMWEs on the thermodynamic stability of the ASDs is quite small while the kinetic stability is significantly decreased even by small LMWE amounts. PC-SAFT and the Kwei equation are suitable tools for predicting the influence of LMWEs on the ASD phase behavior. SN - 1573-904X UR - https://www.unboundmedicine.com/medline/citation/29305717/Influence_of_Low_Molecular_Weight_Excipients_on_the_Phase_Behavior_of_PVPVA64_Amorphous_Solid_Dispersions_ L2 - https://doi.org/10.1007/s11095-017-2316-y DB - PRIME DP - Unbound Medicine ER -