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31 results on '"Kyeremateng, Samuel O."'

2. Predicting the Release Mechanism of Amorphous Solid Dispersions: A Combination of Thermodynamic Modeling and In Silico Molecular Simulation.

Author

Walter, Stefanie, Mileo, Paulo G. M., Afzal, Mohammad Atif Faiz, Kyeremateng, Samuel O., Degenhardt, Matthias, Browning, Andrea R., and Shelley, John C.

Subjects
TERNARY phase diagrams, THERMODYNAMIC molecular model, PHASE transitions, AMORPHOUS substances, THERMODYNAMIC potentials, PHASE separation
Abstract

Background: During the dissolution of amorphous solid dispersion (ASD) formulations, the drug load (DL) often impacts the release mechanism and the occurrence of loss of release (LoR). The ASD/water interfacial gel layer and its specific phase behavior in connection with DL strongly dictate the release mechanism and LoR of ASDs, as reported in the literature. Thermodynamically driven liquid-liquid phase separation (LLPS) and/or drug crystallization at the interface are the key phase transformations that drive LoR. Methods: In this study, a combination of Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) thermodynamic modeling and in silico molecular simulation was applied to investigate the release mechanism and the occurrence LoR of an ASD formulation consisting of ritonavir as the active pharmaceutical ingredient (API) and the polymer, polyvinylpyrrolidone-co-vinyl acetate (PVPVA64). A thermodynamically modeled ternary phase diagram of ritonavir (PVPVA64) and water was applied to predict DL-dependent LLPS in the ASD/water interfacial gel layer. Microscopic Erosion Time Testing (METT) was used to experimentally validate the phase diagram predictions. Additionally, in silico molecular simulation was applied to provide further insights into the phase separation, the release mechanism, and aggregation behavior on a molecular level. Results: Thermodynamic modeling, molecular simulation, and experimental results were consistent and complementary, providing evidence that ASD/water interactions and phase separation are essential factors driving the dissolution behavior and LoR at 40 wt% DL of the investigated ritonavir/PVPVA64 ASD system, consistent with previous studies. Conclusions: This study provides insights into the potential of blending thermodynamic modeling, molecular simulation, and experimental research to comprehensively understand ASD formulations. Such a combined approach can be leveraged as a computational framework to gain insights into the ASD dissolution mechanism, thereby facilitating in silico screening, designing, and optimization of formulations with the benefit of significantly reducing the number of experimental tests. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Impact of surfactant raw material variability on extrudate clarity appearance (transparency) in HME continuous manufacturing.

Author

Lohmann, Claudia A., Bochmann, Esther, and Kyeremateng, Samuel O.

Subjects
POLYSORBATE 80, GLASS transition temperature, AMORPHOUS substances, DIFFERENTIAL scanning calorimetry, MOLECULAR weights
Abstract

The appearance of an extrudate formulation was monitored during hot-melt extrusion (HME) continuous manufacturing over 3 days. The formulation matrix consisted of a polymeric component, copovidone, and a low molecular weight surfactant, polysorbate 80. Based on studies prior to the continuous manufacturing, the desired appearance of the target extrudate is translucent. Although process parameters such as feed rate and screw speed were fixed during the continuous manufacturing, the extrudate appearance changed over time from turbid to translucent. For root-cause investigation, the extrudates were analyzed offline by differential scanning calorimetry (DSC) and advanced polymer chromatography (APC™). Although the polysorbate 80 content of both turbid and translucent extrudates was within target, the glass transition temperature of the turbid extrudate was 2 °C above expected value. The observed turbidity was traced to lot-to-lot variability of the polysorbate 80 used in the continuous manufacturing, where APC™ analysis revealed that the relative content of the low molecular weight component varied from 23% to 27% in correlation with the evolution from turbid to translucent extrudates. This work stresses the importance of taking feeding material variability into account during continuous manufacturing. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Molecular-Level Examination of Amorphous Solid Dispersion Dissolution

Author

Faiz Afzal, Mohammad Atif, primary, Lehmkemper, Kristin, additional, Sobich, Ekaterina, additional, Hughes, Thomas F., additional, Giesen, David J., additional, Zhang, Teng, additional, Krauter, Caroline M., additional, Winget, Paul, additional, Degenhardt, Matthias, additional, Kyeremateng, Samuel O., additional, Browning, Andrea R., additional, and Shelley, John C., additional

Published
2021
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26. Frozen in Time: Kinetically Stabilized Amorphous Solid Dispersions of Nifedipine Stable after a Quarter Century of Storage

Author

Theil, Frank, Anantharaman, Sankaran, Kyeremateng, Samuel O., van Lishaut, Holger, Dreis-Kühne, Sebastian H., Rosenberg, Jörg, Mägerlein, Markus, and Woehrle, Gerd H.

Abstract

Kinetically stabilized amorphous solid dispersions are inherently metastable systems. Therefore, such systems are generally considered prone to recrystallization. In some cases, the formation of crystals will impact the bioavailability of the active pharmaceutical ingredient in these formulations. Recrystallization therefore may present a significant risk for patients as it potentially lowers the effective dose of the pharmaceutical formulation. This study indicates that such metastable formulations may indeed remain fully amorphous even after more than two decades of storage under ambient conditions. Different formulations of nifedipine stored for 25 years were compared with freshly prepared samples. A thorough physicochemical characterization including polarized light microscopy, differential scanning calorimetry, X-ray powder diffraction, and transmission Raman spectroscopy was undertaken. This in-depth characterization indicates no signs of recrystallization in the stored samples. The observations presented here prove that long-term stability of amorphous solid dispersions much beyond the typical shelf life for pharmaceutical formulations is indeed possible by kinetic stabilization alone. These findings implicate a reevaluation of the propensity to recrystallize for kinetically stabilized amorphous solid dispersions.

Published
2017
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27. Long-Term Physical Stability of PVP- and PVPVA-Amorphous Solid Dispersions

Author

Lehmkemper, Kristin, Kyeremateng, Samuel O., Heinzerling, Oliver, Degenhardt, Matthias, and Sadowski, Gabriele

Abstract

The preparation of amorphous solid dispersion (ASD) formulations is a promising strategy to improve the bioavailability of an active pharmaceutical ingredient (API). By dissolving the API in a polymer it is stabilized in its amorphous form, which usually shows higher water solubility than its crystalline counterpart. To prevent recrystallization, the long-term physical stability of ASD formulations is of big interest. In this work, the solubility of the APIs acetaminophen and naproxen in the excipient polymers poly(vinylpyrrolidone) (PVP K25) and poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64) was calculated with three models: the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), the Flory–Huggins model (FH), and an empirical model (Kyeremateng et al., J. Pharm. Sci, 2014, 103, 2847–2858). PC-SAFT and FH were further used to predict the influence of relative humidity (RH) on the API solubility in the polymers. The Gordon–Taylor equation was applied to model the glass-transition temperature of dry ASD and at humid conditions. The calculations were validated by 18 months-long stability studies at standardized storage conditions, 25 °C/0% RH, 25 °C/60% RH, and 40 °C/75% RH. The results of the three modeling approaches for the API solubility in polymers agreed with the experimental solubility data, which are only accessible at high temperatures in dry polymers. However, at room temperature FH resulted in a lower solubility of the APIs in the dry polymers than PC-SAFT and the empirical model. The impact of RH on the solubility of acetaminophen was predicted to be small, but naproxen solubility in the polymers was predicted to decrease with increasing RH with both, PC-SAFT and FH. At 25 °C/60% RH and 40 °C/75% RH, PC-SAFT is in agreement with all results of the long-term stability studies, while FH underestimates the acetaminophen solubility in PVP K25 and PVPVA64.

Published
2017
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