Heat capacities of selected active pharmaceutical ingredients

Štejfa, Vojtěch; Pokorný, Václav; Mathers, Alex; Růžička, Květoslav

doi:10.1016/j.jct.2021.106585

Cited by 15 publications

(14 citation statements)

References 53 publications

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“…The physicochemical properties of the pure materials utilized in this study are presented in Table 3 . Both melting temperature and fusion enthalpy of IBU agree well with the previously published values summarized by Štejfa et al [ 31 ]. The amorphous IBU was obtained by quenching the melt using β = 20 °C min −1 , and its T g was measured during subsequent heating by β = 10 °C min −1 .…”

Section: Resultssupporting

confidence: 90%

“…The amorphous IBU was obtained by quenching the melt using β = 20 °C min −1 , and its T g was measured during subsequent heating by β = 10 °C min −1 . The obtained T g value is in alignment with the results found in the literature, which cover the range from −48 to −45 °C [ 31 ]. The recorded T g of the PLA/PLGA polymers are in good agreement with the general trend typical for this group of polymers described in the literature: T g increases with increasing LA content (e.g., from 35.7 °C for PLGA 50:50 (LA:GA) to 45.3 °C for the PLA 100:0 (LA:GA) according to Pyo Park et al [ 32 ]) and molecular weight of the polymer (e.g., from 42.2 °C for 8000 g/mol PLGA to 52.6 °C 110,000 g/mol PLGA, in accordance with Lee et al [ 33 ]).…”

Section: Resultssupporting

confidence: 89%

“…c The difference between the isobaric molar heat capacity of a liquid and a crystal. The reported equation was derived based on experimental heat capacities published in [ 31 ].…”

Section: Figurementioning

confidence: 99%

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Effect of Copolymer Properties on the Phase Behavior of Ibuprofen–PLA/PLGA Mixtures

et al. 2023

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Prediction of compatibility of the active pharmaceutical ingredient (API) with the polymeric carrier plays an essential role in designing drug delivery systems and estimating their long-term physical stability. A key element in deducing API–polymer compatibility is knowledge of a complete phase diagram, i.e., the solubility of crystalline API in polymer and mutual miscibility of API and polymer. In this work, the phase behavior of ibuprofen (IBU) with different grades of poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA), varying in composition of PLGA and molecular weight of PLGA and PLA, was investigated experimentally using calorimetry and computationally by the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state (EOS). The phase diagrams constructed based on a PC-SAFT EOS modeling optimized using the solubility data demonstrated low solubility at typical storage temperature (25 °C) and limited miscibility (i.e., presence of the amorphous–amorphous phase separation region) of IBU with all polymers studied. The ability of PC-SAFT EOS to capture the experimentally observed trends in the phase behavior of IBU–PLA/PLGA systems with respect to copolymer composition and molecular weight was thoroughly investigated and evaluated.

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 89%

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Effect of Copolymer Properties on the Phase Behavior of Ibuprofen–PLA/PLGA Mixtures

et al. 2023

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“…The reported values for T m , Δ fus H , and T g were measured using the same conditions as the data for binary phase diagrams to ensure the consistency between the two datasets. The fusion thermodynamic properties for IND, IBU, and NAP, as well as T g values for IND and IBU, are in close agreement with those reviewed and summarized by Štejfa et al [ 27 ]. The T g value of NAP was determined in this work based by extrapolation from the measured T g values of binary mixtures with NAP (for details and comparison to the literature values, see Section 3.3.4 ).…”

Section: Resultssupporting

confidence: 89%

Solid–Liquid Equilibrium in Co-Amorphous Systems: Experiment and Prediction

et al. 2023

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In this work, the solid–liquid equilibrium (SLE) of four binary systems combining two active pharmaceutical ingredients (APIs) capable of forming co-amorphous systems (CAMs) was investigated. The binary systems studied were naproxen-indomethacin, naproxen-ibuprofen, naproxen-probucol, and indomethacin-paracetamol. The SLE was experimentally determined by differential scanning calorimetry. The thermograms obtained revealed that all binary mixtures investigated form eutectic systems. Melting of the initial binary crystalline mixtures and subsequent quenching lead to the formation of CAM for all binary systems and most of the compositions studied. The experimentally obtained liquidus and eutectic temperatures were compared to theoretical predictions using the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state and conductor-like screening model for real solvents (COSMO-RS), as implemented in the Amsterdam Modeling Suite (COSMO-RS-AMS). On the basis of the obtained results, the ability of these models to predict the phase diagrams for the investigated API–API binary systems was evaluated. Furthermore, the glass transition temperature (Tg) of naproxen (NAP), a compound with a high tendency to recrystallize, whose literature values are considerably scattered, was newly determined by measuring and modeling the Tg values of binary mixtures in which amorphous NAP was stabilized. Based on this analysis, erroneous literature values were identified.

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“… a See the discussion on various polymorphic forms of some of the considered APIs in Štejfa et al b The reported uncertainties of the fusion data used in this work are (0.2–0.7) K for T fus , (1–3)% for Δ fus H , and higher units of percent up to approx. 10% for Δ fus C p . c Grzesiak et al d Veith et al e Coon et al f Chirico et al g Zhao et al h Paus et al i Štejfa et al j Granberg and Rasmuson k Neau et al l Vasa et al m Svärd et al n Wang et al …”

Section: Introductionmentioning

confidence: 90%

Purely Predicting the Pharmaceutical Solubility: What to Expect from PC-SAFT and COSMO-RS?

Klajmon

2022

Mol. Pharmaceutics

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A pair of popular thermodynamic models for pharmaceutical applications, namely, the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state and the conductor-like screening model for real solvents (COSMO-RS), are thoroughly benchmarked for their performance in predicting the solubility of active pharmaceutical ingredients (APIs) in pure solvents. The ultimate goal is to provide an illustration of what to expect from these progressive frameworks when applied to the thermodynamic solubility of APIs based on activity coefficients in a purely predictive regime without specific experimental solubility data (the fusion properties of pure APIs were taken from experiments). While this kind of prediction represents the typical modus operandi of the first-principles-aided COSMO-RS, PC-SAFT is a relatively highly parametrized model that relies on experimental data, against which its pure-substance and binary interaction parameters (kij) are fitted. Therefore, to make this benchmark as fair as possible, we omitted any binary parameters of PC-SAFT (that is, kij = 0 in all cases) and preferred pure-substance parameter sets for APIs not trained to experimental solubility data. This computational approach, together with a detailed assessment of the obtained solubility predictions against a large experimental data set, revealed that COSMO-RS convincingly outperformed PC-SAFT both qualitatively (that is, COSMO-RS was better in solvent ranking) and quantitatively, even though the former is independent of both substance-and mixture-specific experimental data. Regarding quantitative comparison, COSMO-RS outperformed PC-SAFT for nine of the ten APIs and for 63 % of the API-solvent systems, with root-mean-square deviations of the predicted data from the entire experimental data set being 0.82 and 1.44 log units, respectively.The results were further analyzed to expand the picture of the performance of both models with respect to the individual APIs and solvents. Interestingly, in many cases, both models were found to qualitatively incorrectly predict the direction of deviations from ideality. Furthermore, we examined how the solubility predictions from both models are sensitive to different API parametrizations.

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Heat capacities of selected active pharmaceutical ingredients

Cited by 15 publications

References 53 publications

Effect of Copolymer Properties on the Phase Behavior of Ibuprofen–PLA/PLGA Mixtures

Effect of Copolymer Properties on the Phase Behavior of Ibuprofen–PLA/PLGA Mixtures

Solid–Liquid Equilibrium in Co-Amorphous Systems: Experiment and Prediction

Purely Predicting the Pharmaceutical Solubility: What to Expect from PC-SAFT and COSMO-RS?

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