The step-wise dissolution method: An efficient DSC-based protocol for verification of predicted API–polymer compatibility

Mathers, Alex; Pechar, Matouš; Hassouna, Fatima; Fulem, Michal

doi:10.1016/j.ijpharm.2023.123604

Cited by 4 publications

(5 citation statements)

References 63 publications

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“…Building on the analysis presented in the preceding paragraph, there are notable differences in the performance of CS dsp FV across individual systems. The accuracy is high for many systems, e.g., GSF–PVPK25, IBP–PVA, and NPX–PVPK30 with AAD values below 3% (the very lowest AAD values obtained approach the upper limit of the experimental uncertainty). However, the accuracy is significantly worse for some other systems, e.g., IBP–EUD and IBP–PLGA50 with AAD of 34% and 53%, respectively.…”

Section: Resultsmentioning

confidence: 98%

“…As can be seen in Figure 7, certain polymer types consistently exhibit better compatibility with the API than others. Specifically, PVP polymers typically have the best compatibility with API, followed by PVPVAc64, 10,22,32,67 while the biocompatible PLGA copolymers are reported to have relatively poor compatibility (though being sufficient for formulation purposes). 40,112 These experimentally observed "behavioral" patterns of polymers appear to be captured very well by the predictions made by CS dsp FV .…”

Section: Polymer Ranking As Discussed In Section 31 the Results From ...mentioning

confidence: 99%

“…To evaluate the predictive performance of COSMO-SAC for ASD, we used reliable and consistent experimental API solubility data. These data were provided by Mathers and co-workers ,− ,,− and obtained using differential scanning calorimetry (DSC). , An overview of all considered API–polymer systems and the individual experimental solubility data sources is given in Table .…”

Section: Methodsmentioning

confidence: 99%

“…Specifically, the absence of an absolute value in AD allows for the determination of whether the COSMO-SAC model has a tendency to under- or overestimate the experimental data. Further, the average absolute relative deviation (AARD) was considered because of its routine usage in the ASD-oriented literature ,,,, A A R D ( w A P I ) = 1 N ∑ i = 1 N true| normalΔ w normalA normalP normalI w normalA normalP normalI exp true| i …”

Section: Methodsmentioning

confidence: 99%

“…As an exemplary sample, a set of seven API, nine polymers (both homo- and copolymers), and 35 different API–polymer systems thereof is considered, for which consistent and reliable experimental solubility data were measured by Mathers and co-workers in Prague in recent years. ,− These data were used to evaluate the performance of COSMO-SAC. An overview with chemical identifiers of the API and polymers considered in this work is given in Tables S1 and S2, respectively, in the Supporting Information (SI).…”

Section: Introductionmentioning

confidence: 99%

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COSMOPharm: Drug–Polymer Compatibility of Pharmaceutical Amorphous Solid Dispersions from COSMO-SAC

Antolović,

Vrabec,

Klajmon

2024

Mol. Pharmaceutics

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The quantum mechanics-aided COSMO-SAC activity coefficient model is applied and systematically examined for predicting the thermodynamic compatibility of drugs and polymers. The drug−polymer compatibility is a key aspect in the rational selection of optimal polymeric carriers for pharmaceutical amorphous solid dispersions (ASD) that enhance drug bioavailability. The drug−polymer compatibility is evaluated in terms of both solubility and miscibility, calculated using standard thermodynamic equilibrium relations based on the activity coefficients predicted by COSMO-SAC. As inherent to COSMO-SAC, our approach relies only on quantum-mechanically derived σ-profiles of the considered molecular species and involves no parameter fitting to experimental data. All σ-profiles used were determined in this work, with those of the polymers being derived from their shorter oligomers by replicating the properties of their central monomer unit(s). Quantitatively, COSMO-SAC achieved an overall average absolute deviation of 13% in weight fraction drug solubility predictions compared to experimental data. Qualitatively, COSMO-SAC correctly categorized different polymer types in terms of their compatibility with drugs and provided meaningful estimations of the amorphous−amorphous phase separation. Furthermore, we analyzed the sensitivity of the COSMO-SAC results for ASD to different model configurations and σ-profiles of polymers. In general, while the free volume and dispersion terms exerted a limited effect on predictions, the structures of oligomers used to produce σ-profiles of polymers appeared to be more important, especially in the case of strongly interacting polymers. Explanations for these observations are provided. COSMO-SAC proved to be an efficient method for compatibility prediction and polymer screening in ASD, particularly in terms of its performance−cost ratio, as it relies only on first-principles calculations for the considered molecular species. The open-source nature of both COSMO-SAC and the Python-based tool COSMOPharm, developed in this work for predicting the API−polymer thermodynamic compatibility, invites interested readers to explore and utilize this method for further research or assistance in the design of pharmaceutical formulations.

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Section: Resultsmentioning

confidence: 98%

Section: Polymer Ranking As Discussed In Section 31 the Results From ...mentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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COSMOPharm: Drug–Polymer Compatibility of Pharmaceutical Amorphous Solid Dispersions from COSMO-SAC

Antolović,

Vrabec,

Klajmon

2024

Mol. Pharmaceutics

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Heat capacities of active pharmaceutical ingredients nifedipine, griseofulvin, probucol and 5,5-diphenylhydantoin

Štejfa,

Vojtíšková,

Pokorný

et al. 2024

J Therm Anal Calorim

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The isobaric condensed-phase heat capacities of selected pharmaceutical active ingredients (APIs), namely nifedipine (CAS RN: 21829-25-4), griseofulvin (CAS RN: 126-07-8), probucol (CAS RN: 23288-49-5) and 5,5-diphenylhydantoin (CAS RN: 57-41-0), were determined over a wide temperature range starting from 2 K by combination of relaxation (heat pulse) calorimetry, Tian-Calvet calorimetry and power-compensated differential scanning calorimetry. Heat capacity measurements were taken for clearly specified polymorphs, a liquid phase (including subcooled liquid) and a glassy amorphous phase, if feasible. For 5,5-diphenylhydantoin, a heat capacity anomaly was detected in the temperature range 160 to 190 K and interpreted based on additional calorimetric and temperature-variable crystallographic measurements as a sequence of two phase transitions, which are reported for the first time in this work. Based on the determined phase behavior and heat capacity data from near 0 K, standard thermodynamic functions for crystalline and liquid phases were calculated for all APIs studied. This work significantly extends the availability of reliable heat capacity data and related thermodynamic properties for APIs required for modeling their solubility and other applications involving thermodynamic modeling.

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A unifying approach to drug-in-polymer solubility prediction: Streamlining experimental workflow and analysis

Larsen,

Meiland,

Tzdaka

et al. 2024

European Journal of Pharmaceutics and Biopharmaceutics

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The step-wise dissolution method: An efficient DSC-based protocol for verification of predicted API–polymer compatibility

Cited by 4 publications

References 63 publications

COSMOPharm: Drug–Polymer Compatibility of Pharmaceutical Amorphous Solid Dispersions from COSMO-SAC

COSMOPharm: Drug–Polymer Compatibility of Pharmaceutical Amorphous Solid Dispersions from COSMO-SAC

Heat capacities of active pharmaceutical ingredients nifedipine, griseofulvin, probucol and 5,5-diphenylhydantoin

A unifying approach to drug-in-polymer solubility prediction: Streamlining experimental workflow and analysis

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