Contribution of low-frequency Raman spectroscopy to determine the solubility curves of drugs in polymers: The case of paracetamol/PVP

Latreche, Mansour; willart, Jean-François; Paccou, Laurent; Guinet, Yannick; Danède, Florence; Hédoux, Alain

doi:10.1016/j.ejpb.2020.07.012

Cited by 8 publications

(5 citation statements)

References 28 publications

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“…Because the utilization of this DSC-based protocol for IND solubility measurement in PVP K12, Latreche et al 38 published a study on the application of low-frequency Raman spectroscopy for API−polymer SLE determination, in which a comparable annealing method was used. In their work, a so-called "molecular and crystalline dispersion" of paracetamol in PVP K12 was subjected to a procedure similar to that described above to obtain a series of T g values, which were subsequently converted to API solubilities using the G−T equation [G−T (2); see Section 2.4.1 below].…”

Section: S-wd Methodmentioning

confidence: 99%

Comparative Study of DSC-Based Protocols for API–Polymer Solubility Determination

et al. 2021

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Knowledge of the active pharmaceutical ingredient (API) solubility in a polymer is imperative for successful amorphous solid dispersion design and formulation but acquiring this information at storage temperature is challenging. Various solubility determination methods have been established, which utilize differential scanning calorimetry (DSC). In this work, three commonly used DSC-based protocols [i.e., melting point depression (MPD), recrystallization, and zero-enthalpy extrapolation (Z-EE)] and a method that we have developed called "stepwise dissolution" (S-WD) were analyzed. For temperature−composition phase diagram construction, two glass-transition temperature equations (i.e., those of Gordon−Taylor and Kwei) and three solid−liquid equilibrium curve modeling approaches [i.e., the Flory−Huggins model, an empirical equation, and the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state (EOS)] were considered. Indomethacin (IND) and Kollidon 12 PF (PVP K12) were selected as the API and polymer, respectively. An annealing time investigation revealed that the IND−PVP K12 dissolution process was remarkably faster than demixing, which contradicted previously published statements. Thus, the recrystallization method overestimated the solubility of IND in PVP K12 when a 2-h time of annealing was set as the benchmark. Likewise, the MPD and Z-EE methods overestimated the API solubility because of unreliable IND melting endotherm evaluation at lower API loadings and a relatively slow heating rate, respectively. When the experimental results obtained using the S-WD method (in conjunction with the Kwei equation) were applied to the PC-SAFT EOS, which was regarded as the most reliable combination, the predicted IND solubility in PVP K12 at T = 25 °C was approximately 40 wt %. When applicable, the S-WD method offers the advantage of using a limited number of DSC sample pans and API−polymer physical mixture compositions, which is both cost-and time-effective.

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Section: S-wd Methodmentioning

confidence: 99%

Comparative Study of DSC-Based Protocols for API–Polymer Solubility Determination

et al. 2021

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“…Considering the intrinsic simplicity of the experimental setup, this technique could potentially be adapted for in-line analysis of solid dosage forms during their manufacture or storage and help to identify potential problems without irreversibly damaging the product. Additionally, since the LFR region not only allows us to distinguish various solid-state forms but also encompasses information related to molecular mobility among other properties, 27 micro-SOLFRS has a potential for very interesting and exciting applications in the near future.…”

Section: ■ Conclusionmentioning

confidence: 99%

Pseudo-3D Subsurface Imaging of Pharmaceutical Solid Dosage Forms Using Micro-spatially Offset Low-Frequency Raman Spectroscopy

2021

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A new combinatory Raman subtechnique of low-frequency and micro-spatially offset Raman spectroscopy (denoted micro-SOLFRS) is demonstrated via analysis of pharmaceutical solid dosage forms. A variety of different (multilayer/multicomponent) model systems comprising celecoxib, α-lactose (the anhydrous and monohydrate form), and polyvinylpyrrolidone (PVP) were probed to test the potency of this newly developed technique to, for example, provide qualitative and quantitative information on surface and subsurface layer characteristics, including their thicknesses as well as enable monitoring of surface-driven solid-state form transformations. A simultaneous collection of low- and, the more commonly used, mid-frequency data enabled a direct comparison between these spectral regions, where the low-frequency domain (hence, micro-SOLFRS) proved superior for every respective analysis carried out herein.

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“…The low-frequency Raman region is particularly useful for tracking and understanding polymorphic [ 23 , 26 ] or solid-state transitions; examples of its use include the crystallisation of amorphous indomethacin [ 32 ], stabilisation of amorphous indomethacin with amino acids [ 25 ], transformation of caffeine under different conditions [ 31 , 33 , 34 ], and exploring dehydration processes [ 20 , 35 , 36 ]. Drug–polymer solubility [ 37 ] and the associated stabilisation effects of drug–polymer formulations [ 38 ] have also been demonstrated. Low-frequency Raman has been demonstrated as advantageous with regard to the quantification of active pharmaceutical ingredients (APIs) with examples including carbamazepine [ 27 ], griseofulvin [ 22 ], sulfathiazole polytypes [ 39 ], piroxicam [ 28 ], and caffeine-glutaric acid cocrystals [ 40 ], allowing for the detection of crystalline drugs in amorphous solid dosage forms and the determination of the solid-state polymorphic transformations [ 28 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

In Situ Monitoring of Drug Precipitation from Digesting Lipid Formulations Using Low-Frequency Raman Scattering Spectroscopy

et al. 2023

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Low-frequency Raman spectroscopy (LFRS) is a valuable tool to detect the solid state of amorphous and crystalline drugs in solid dosage forms and the transformation of drugs between different polymorphic forms. It has also been applied to track the solubilisation of solid drugs as suspensions in milk and infant formula during in vitro digestion. This study reports the use of LFRS as an approach to probe drug precipitation from a lipid-based drug delivery system (medium-chain self-nanoemulsifying drug delivery system, MC-SNEDDS) during in vitro digestion. Upon lipolysis of the digestible components in MC-SNEDDS containing fenofibrate as a model drug, sharp phonon peaks appeared at the low-frequency Raman spectral region (<200 cm−1), indicating the precipitation of fenofibrate in a crystalline form from the formulation. Two multivariate data analysis approaches (principal component analysis and partial least squares discriminant analysis) and one univariate analysis approach (band ratios) were explored to track these spectral changes over time. The low-frequency Raman data produces results in good agreement with in situ small angle X-ray scattering (SAXS) measurements with all data analysis approaches used, whereas the mid-frequency Raman requires the use of PLS-DA to gain similar results. This suggests that LFRS can be used as a complementary, and potentially more accessible, technique to SAXS to determine the kinetics of drug precipitation from lipid-based formulations.

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Contribution of low-frequency Raman spectroscopy to determine the solubility curves of drugs in polymers: The case of paracetamol/PVP

Cited by 8 publications

References 28 publications

Comparative Study of DSC-Based Protocols for API–Polymer Solubility Determination

Comparative Study of DSC-Based Protocols for API–Polymer Solubility Determination

Pseudo-3D Subsurface Imaging of Pharmaceutical Solid Dosage Forms Using Micro-spatially Offset Low-Frequency Raman Spectroscopy

In Situ Monitoring of Drug Precipitation from Digesting Lipid Formulations Using Low-Frequency Raman Scattering Spectroscopy

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