The underestimated contribution of the solvent to the phase behavior of highly drug loaded amorphous solid dispersions

Dedroog, Sien; Boel, Eline; Kindts, Célestine; Appeltans, Bernard; Mooter, Guy Van den

doi:10.1016/j.ijpharm.2021.121201

Cited by 7 publications

(18 citation statements)

References 45 publications

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“…Regarding the classification set forth by Van Eerdenbrugh et al, it can thus be concluded that both model compounds can be classified as glass forming ability (GFA) Class I compounds in MeOH [ 20 , 21 ]. In the literature, NAP is manifold defined as a fast crystallizer and, moreover, its high crystallization tendency appears to be irrespective of the solvent applied, as previously reported by our research group [ 11 , 22 , 23 , 24 ]. The rapid crystallization behavior observed for NAPME is, however, in contrast with the findings of Minecka et al [ 22 ].…”

Section: Resultssupporting

confidence: 65%

“…In solid dispersions, the polymer acts as a stabilizer via anti-plasticizing effects, viscosity effects and potential drug–polymer intermolecular interactions to prevent drug–polymer phase separation and drug crystallization [ 6 , 7 , 8 , 9 ]. An ASD or glass solution is, however, only thermodynamically stable (i.e., the drug will never crystallize), in case the drug content is below its thermodynamic solubility limit in the polymer [ 10 , 11 ]. The persisting trend to lower the pill burden to promote patient therapeutic compliance requires the implementation of as high as possible drug loadings within the polymer [ 5 , 12 , 13 ].…”

Section: Introductionmentioning

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: Resultssupporting

confidence: 65%

Section: Introductionmentioning

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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“…For spray drying, the solvent should measure up to the following criteria: have a common solubilizing capacity for API and polymer (and other additives), an acceptable viscosity, a low toxicity, and a high volatility and be noncombustive, and the solutes should have an acceptable chemical stability in solution . Although selecting a solvent in which all compounds have a sufficiently high solubility is critical, it was found in previous work that the importance of the solubility for the phase behavior of ASDs should not be overestimated . More specifically, the solvent determined the amount of API that could be kinetically stabilized in the poly(vinylpyrrolidone- co -vinyl acetate) (PVPVA) matrix immediately after preparation, yet there was no relation between this amount and the equilibrium solubility of the API in the respective solvent.…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, the evaporation kinetics of seven single organic solvents, i.e., MeOH, ethanol (EtOH), isopropanol (PrOH), acetonitrile (ACN), Ac, DCM, and ethyl acetate (EtAc), were investigated by means of thermal gravimetric analysis (TGA). These solvents were selected as it was demonstrated in previous work that their different polarity and volatility could give rise to a diverse phase behavior of ASDs . The influence of compounds that dissolve in/mix with the solvent on the evaporation behavior was also of interest: PVPVA, fenofibrate (FNB), naproxen (NAP), and combinations of these APIs with PVPVA were studied.…”

Section: Introductionmentioning

confidence: 99%

“…NAP was selected as it can hydrogen bond with PVPVA: its carboxylic acid group can act as a hydrogen donor for the carbonyl group of PVPVA. , In contrast, FNB has no hydrogen bonding potential with PVPVA as it has no hydrogen donor groups . However, it was found that the solvent had a large impact on the physical state of ASDs of FNB, with the maximum amount of drug that could be kinetically stabilized ranging from 5 wt % using MeOH to 25 wt % using Ac/EtAc . Besides the expected effect of the solutes on the vapor pressure, also interactions between API–polymer–solvent could interfere with the evaporation process .…”

Section: Introductionmentioning

confidence: 99%

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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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Use of surfactant-based amorphous solid dispersions for BDDCS class II drugs to enhance oral bioavailability: A case report of resveratrol

Jia

Chen

Cheng

et al. 2023

International Journal of Pharmaceutics

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The underestimated contribution of the solvent to the phase behavior of highly drug loaded amorphous solid dispersions

Cited by 7 publications

References 45 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

Use of surfactant-based amorphous solid dispersions for BDDCS class II drugs to enhance oral bioavailability: A case report of resveratrol

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