The Secondary Drying and the Fate of Organic Solvents for Spray Dried Dispersion Drug Product

Hsieh, Daniel; Yue, Hongfei; Nicholson, Sarah J.; Roberts, Dewi; Schild, Richard L.; Gamble, John F.; Lindrud, Mark

doi:10.1007/s11095-014-1577-y

Cited by 15 publications

(15 citation statements)

References 12 publications

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“…We are interested in the CMF method, mainly due to its mathematical simplicity and straightforwardness for the determination of the kinetic triplet. Particularly, we are interested in using CMF for analyzing single-step isothermal solid-state reactions (ISSRs) [22], which usually take place during the drying process of pharmaceutical hydrates/solvates [1][2][3][4]21,[23][24][25][26]. The most crucial step when performing CMF is to identify the 'best' candidate model (BCM) for a particular ISSR and then the complete kinetic triplet is calculated.…”

Section: Introductionmentioning

confidence: 99%

COMF: Comprehensive Model-Fitting Method for Simulating Isothermal and Single-Step Solid-State Reactions

2020

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It is well known that the implementation of the conventional model-fitting (CMF) method leads to several indistinguishable ‘best’ candidate models (BCMs) for a single-step isothermal solid-state reaction (ISSR), meaning that subjective selection becomes unavoidable. Here, we developed a more robust comprehensive model-fitting method (COMF) which, while maintaining the mathematical simplicity of CMF, utilizes a ranking criterion that enables automatic and unambiguous determination of the BCM. For each model evaluated, COMF, like CMF, fits the integral reaction rate, but, unlike CMF, it also fits the experimental conversion fraction and reaction speed. From this, three different determination coefficients are calculated and combined to rank the considered models. To validate COMF, we used two sets of experimental kinetic data from the literature regarding the isothermal desolvation of pharmaceutical solvates: (i) tetrahydrofuran solvates of sulfameter, and (ii) methanol solvates of ciclesonide. Our results suggest that from an algorithmic perspective, COMF could become the model-fitting method of choice for ISSRs making the selection of BCM easier and more reliable.

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Section: Introductionmentioning

confidence: 99%

COMF: Comprehensive Model-Fitting Method for Simulating Isothermal and Single-Step Solid-State Reactions

2020

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“…It should be noted that there is a linear behavior from the beginning of the mass transfer process until half of the ethanol is removed, a characteristic of the Fickian diffusion. 5,6 It should be noted that the drying experiment at 50 °C and 20 mmHg continued until no further weight change was observed to determine the amount of ethanol removed via the diffusion process (Figure 9).…”

Section: Resultsmentioning

confidence: 99%

“…Integrated Sorption Chamber. A microprocessor controlled vacuum oven 5 (VWR model 1430M) was modified and converted to an integrated sorption chamber. This chamber was equipped with a load cell (Sartorius WZA523-CW), a Raman spectrometer (Kaiser Optical System Inc. model PhAT system analyzer), and an infrared (IR) based temperature camera (FLIR T240).…”

Section: Experimental and Theoretical Approachesmentioning

confidence: 99%

“…The partial differential eq 1 can be solved by the method of separation of variables, and its solution is available in the literature. 5 The solution of eq 1 in terms of concentration as a function of time and location can be integrated from −l to +l to provide the measurable quantity in terms of weight loss as a function of drying time as follows:…”

Section: Experimental and Theoretical Approachesmentioning

confidence: 99%

“…This kind of relationship can be obtained from the solution of eq 1 via the Laplace transformation, as described in the literature. 5,6 The solution from such transformations is provided as follows:…”

Section: Experimental and Theoretical Approachesmentioning

confidence: 99%

See 2 more Smart Citations

From Drying Kinetics, Solvate Structure, Particle Morphology, and Modeling to Optimal Drying Protocol

Hsieh

Gao

Huang

et al. 2017

Org. Process Res. Dev.

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The mechanistic understanding of three key active pharmaceutical ingredient (API) drying elements: drying kinetics, physical property control, and stability control, is critical for downstream formulation development and manufacture. The objective of this study was to collect drying kinetic data through the use of a laboratory integrated sorption chamber to elucidate the drying mechanism and thereby establish a drying model. In addition, the collection of drying kinetic data would provide a greater understanding of the solvent to API ratio as well as the API stability to help develop a large-scale drying protocol. The study material is an ethanol solvate (ethanolate) of the API. There is no fundamental crystal structure change upon drying of the solvate in the temperature range from 50 to 90 °C, and the drying kinetic data show that the molar ratio of ethanol to API is 1:1. This is confirmed by X-ray crystallography. An analysis of the drying kinetics showed that the diffusion of ethanol through the crystal lattice provided the primary mass transfer resistance, which can be simulated using the Fickian principle of diffusion through a slab. The diffusion coefficients from 50 to 90 °C at 20 mmHg were found to be strongly temperature-dependent and fit well using an Arrhenius type relationship. The activation energy for diffusion was then determined from this relationship. By using these diffusion parameters, the drying curves at various temperatures were generated to predict the drying time to meet the final ethanol specification. The predicted drying time was in good agreement with experimental drying data at high temperatures (80 and 90 °C) but shorter than that observed when drying at lower temperatures (between 50 and 70 °C). Thermal stability data showed that the compound is stable at drying temperatures equal or below 70 °C. Drying data from this study are generated from a static balance. Hence, the effect of shear forces imposed from cake depth and dryer agitation on particle morphology, physical stability of the desolvated API, and drying time needs to be studied to generate the optimal drying protocol for large-scale operation.

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Development of a Control Strategy for Benzene Impurity in HPMCAS-Stabilized Spray-Dried Dispersion Drug Products Using a Science-Based and Risk-Based Approach

et al. 2015

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The Secondary Drying and the Fate of Organic Solvents for Spray Dried Dispersion Drug Product

Cited by 15 publications

References 12 publications

COMF: Comprehensive Model-Fitting Method for Simulating Isothermal and Single-Step Solid-State Reactions

COMF: Comprehensive Model-Fitting Method for Simulating Isothermal and Single-Step Solid-State Reactions

From Drying Kinetics, Solvate Structure, Particle Morphology, and Modeling to Optimal Drying Protocol

Development of a Control Strategy for Benzene Impurity in HPMCAS-Stabilized Spray-Dried Dispersion Drug Products Using a Science-Based and Risk-Based Approach

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