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Physical Stability of Amorphous Solid Dispersions: a Physicochemical Perspective with Thermodynamic, Kinetic and Environmental Aspects

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Abstract

Purpose

Amorphous solid dispersions (ASDs) have been widely used in the pharmaceutical industry for solubility enhancementof poorly water-soluble drugs. The physical stability, however, remainsone of the most challenging issues for the formulation development.Many factors can affect the physical stability via different mechanisms, and therefore an in-depth understanding on these factors isrequired.

Methods

In this review, we intend to summarize the physical stability of ASDsfrom a physicochemical perspective whereby factors that can influence the physical stability areclassified into thermodynamic, kinetic and environmental aspects.

Results

The drug-polymer miscibility and solubility are consideredas the main thermodynamicfactors which may determine the spontaneity of the occurrence of the physical instabilityof ASDs. Glass-transition temperature,molecular mobility, manufacturing process,physical stabilityof amorphous drugs, and drug-polymerinteractionsareconsideredas the kinetic factors which areassociated with the kinetic stability of ASDs on aging. Storage conditions including temperature and humidity could significantly affect the thermodynamicand kineticstabilityof ASDs.

Conclusion

When designing amorphous solid dispersions, it isrecommended that these thermodynamic, kinetic and environmental aspects should be completely investigatedand compared to establish rationale formulations for amorphous solid dispersions with high physical stability.

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Abbreviations

API:

Active pharmaceutical ingredient

ASD:

Amorphous solid dispersion

DSC:

Differential scanning calorimetry

FDA:

Food and drug administration

FT-IR:

Fourier transform infrared spectroscopy

HPMCAS:

Hydroxypropyl cellulose acetate succinate

MTDSC:

Modulated temperature differential scanning calorimetry

NMR:

Nuclear magnetic resonance spectroscopy

PC-SAFT:

Perturbed-chain statistical associating fluid theory

PEG:

Polyethylene glycol

PLGA:

Poly lactic-co-glycolic acid

PVP:

Polyvinylpyrrolidone

PVP K12:

Polyvinylpyrrolidone (Mw = 3500)

PVPVA64:

Vinylpyrrolidone-vinyl acetate copolymer[60:40]

Tg :

Glass transition temperature

Vitamin E TPGS :

D-α-tocopheryl polyethylene glycol succinate

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors would like to thank Dr. Sheng Qi at University of East Anglia for the previous discussion. This work is supported by the National Natural Science Foundation of China [Grant numbers 81,603,059]; “Jiangsu Shuangchuang” Program; and Top-notch Academic Programs Project of Jiangsu Higher Education Institutions [Grant numbers PPZY2015B146].

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  1. School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, People’s Republic of China

    Xia Lin, Yang Hu, Lei Liu, Lili Su, Na Li, Jing Yu & Ziyi Yang

  2. School of Pharmacy, Nantong University, No. 19 Qixiu Road, Nantong, 226001, China

    Bo Tang

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  1. Xia Lin
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Correspondence to Ziyi Yang.

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Lin, X., Hu, Y., Liu, L. et al. Physical Stability of Amorphous Solid Dispersions: a Physicochemical Perspective with Thermodynamic, Kinetic and Environmental Aspects. Pharm Res 35, 125 (2018). https://doi.org/10.1007/s11095-018-2408-3

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