Solvent influence on manufacturability, phase behavior and morphology of amorphous solid dispersions prepared via bead coating

Boel, Eline; Giacomini, Flavia; Mooter, Guy Van den

doi:10.1016/j.ejpb.2021.07.013

Cited by 4 publications

(3 citation statements)

References 26 publications

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“…For the formulation with 45% drug weight fraction, a T m,average of 97.2 °C was found (associated with 1.4% crystalline content) and for the 50% drug loading formulation, a T m,average of 108.7 °C was detected (associated with 3.0% crystalline content), as reported in Table 2 . The increasing T m,average with increasing drug load in the formulation is attributed to the lower amount of polymer able to dissolve NAP upon heating during the mDSC measurement, hence less melting point depression [ 25 ]. By comparison, the T m of pure NAP was found to be 154.4 °C (see Figure 2 A).…”

Section: Resultsmentioning

confidence: 99%

“…To exemplify, the difference between the T bed and the T g of NAP_40_PVP-VA prepared with bead coating is approximately 17 °C, while the difference between the T outlet and the T g of NAP_40_PVP-VA prepared with spray drying amounts to only 9 °C. The fact that the difference in maximum achievable drug loading between the two ASD preparation techniques is rather small can be explained by the presence of drug–polymer interactions in combination with the short timeframe over which solvent evaporation occurs [ 25 ]. FTIR spectra were in accordance with available literature data and hence confirm that NAP and PVP-VA form an interacting system via hydrogen bonds (see Figure S1, Supporting Information ) [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

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The Value of Bead Coating in the Manufacturing of Amorphous Solid Dispersions: A Comparative Evaluation with Spray Drying

et al. 2022

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Despite the fact that an amorphous solid dispersion (ASD)-coated pellet formulation offers potential advantages regarding the minimization of physical stability issues, there is still a lack of in-depth understanding of the bead coating process and its value in relation to spray drying. Therefore, bead coating and spray drying were both evaluated for their ability to manufacture high drug-loaded ASDs and for their ability to generate physically stable formulations. For this purpose, naproxen (NAP)–poly(vinyl-pyrrolidone-co-vinyl acetate) (PVP-VA) was selected as an interacting drug–polymer model system, whilst naproxen methyl ester (NAPME)–PVP-VA served as a non-interacting model system. The solvent employed in this study was methanol (MeOH). First, a crystallization tendency study revealed the rapid crystallization behavior of both model drugs. In the next step, ASDs were manufactured with bead coating as well as with spray drying and for each technique the highest possible drug load that still results in an amorphous system was defined via a drug loading screening approach. Bead coating showed greater ability to manufacture high drug-loaded ASDs as compared to spray drying, with a rather small difference for the interacting drug–polymer model system studied but with a remarkable difference for the non-interacting system. In addition, the importance of drug–polymer interactions in achieving high drug loadings is demonstrated. Finally, ASDs coated onto pellets were found to be more physically stable in comparison to the spray dried formulations, strengthening the value of bead coating for ASD manufacturing purposes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The Value of Bead Coating in the Manufacturing of Amorphous Solid Dispersions: A Comparative Evaluation with Spray Drying

et al. 2022

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“…The different effect of PVPVA on the drying rate of organic solvents might also have implications for the particle morphology. For instance, it has been described by Boel et al that the difference in evaporation rate of MeOH and Ac during fluid bed coating was responsible for the morphology of bead coated ASDs of felodipine, where a porous coating was observed for the faster evaporating Ac compared to a homogeneous coating for the slower evaporating MeOH . However, microscopic evaluation of PVPVA particles spray dried with the seven different solvents revealed that all were collapsed (except for PrOH), hence, the difference in evaporation behavior could not be directly related to the morphology of spray-dried PVPVA particles (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Gaining Insight into the Role of the Solvent during Spray Drying of Amorphous Solid Dispersions by Studying Evaporation Kinetics

2022

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Spray drying is one of the most commonly used manufacturing techniques for amorphous solid dispersions (ASDs). During spray drying, very fast solvent evaporation is enabled by the generation of small droplets and exposure of these droplets to a heated drying gas. This fast solvent evaporation leads to an increased viscosity that enables kinetic trapping of an active pharmaceutical ingredient (API) in a polymer matrix, which is favorable for the formulation of supersaturated, kinetically stabilized ASDs. In this work, the relation between the solvent evaporation rate and the kinetic stabilization of highly drug-loaded ASDs was investigated. Accordingly, thermal gravimetric analysis (TGA) was employed to study the evaporation kinetics of seven organic solvents and the influence of solutes, i.e., poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA), fenofibrate (FNB), and naproxen (NAP), on the evaporation behavior. At 10 °C below the boiling point of the respective solvent, methanol (MeOH) had the lowest evaporation rate and dichloromethane (DCM) had the highest. PVPVA decreased the evaporation rate for all solvents, yet this effect was more pronounced for the relatively faster evaporating solvents. The APIs had opposite effects on the evaporation process: FNB increased the evaporation rate, while NAP decreased it. The latter might indicate the presence of interactions between NAP and the solvent or NAP and PVPVA, which was further investigated using Fourier transform−InfraRed (FT-IR) spectroscopy. Based on these findings, spray drying process parameters were adapted to alter the evaporation rate. Increasing the evaporation rate of MeOH and DCM enabled the kinetic stabilization of higher drug loadings of FNB, while the opposite trend was observed for ASDs of NAP. Even when higher drug loadings could be kinetically stabilized by adapting the process parameters, the improvement was limited, demonstrating that the phase behavior of these ASDs of FNB and NAP immediately after preparation was predominantly determined by the API−polymer−solvent combination rather than the process parameters applied.

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The persistence and crystallization behavior of atorvastatin calcium amorphous dispersions in polyvinylpyrrolidone

Tizaoui

Galai²,

Clevers

et al. 2022

Journal of Drug Delivery Science and Technology

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Solvent influence on manufacturability, phase behavior and morphology of amorphous solid dispersions prepared via bead coating

Cited by 4 publications

References 26 publications

The Value of Bead Coating in the Manufacturing of Amorphous Solid Dispersions: A Comparative Evaluation with Spray Drying

The Value of Bead Coating in the Manufacturing of Amorphous Solid Dispersions: A Comparative Evaluation with Spray Drying

Gaining Insight into the Role of the Solvent during Spray Drying of Amorphous Solid Dispersions by Studying Evaporation Kinetics

The persistence and crystallization behavior of atorvastatin calcium amorphous dispersions in polyvinylpyrrolidone

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