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Influence of Polymers on the Physical and Chemical Stability of Spray-dried Amorphous Solid Dispersion: Dipyridamole Degradation Induced by Enteric Polymers

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Abstract

Amorphous solid dispersions (ASDs) are inherently unstable because of high internal energy. Evaluating physical and chemical stability during the process and storage is essential. Numerous researches have demonstrated how polymers influence the drug precipitation and physical stability of ASDs, while the influence of polymers on the chemical stability of ASDs is often overlooked. Therefore, this study aimed to investigate the effect of polymers on the physical and chemical stability of spray-dried ASDs using dipyridamole (DP) as a model drug. Proper polymers were selected by assessing their abilities to inhibit drug recrystallization in supersaturated solutions. HPMC E5, Soluplus®, HPMCP-55, and HPMCAS-LP were shown to be effective stabilizers. The optimized formulations were further stored at a high temperature (60 °C) and high humidity (40 °C, 75% RH) for 2 months, and their physical and chemical stability was evaluated using polarizing optical microscopy, FTIR, HPLC, and mass spectrometry (MS). In general, crystallization was observed in all samples, which indicated the physical instability under stressed storage conditions. Also, it was noted that the polymers in ASDs rather than physical mixtures, induced a dramatic drug degradation after being exposed to a high temperature (HPMCP-55 > 80% and HPMCAS-LP > 50%) and high humidity (HPMCP-55 > 40% and HPMCAS-LP > 10%). The MS analysis further confirmed the degradation products, which might be generated from the reaction between dipyridamole and phthalic anhydride decomposed from HPMCP-55 and HPMCAS-LP. Overall, the exposure of ASDs to stressed conditions resulted in recrystallization and even the chemical degradation induced by polymers.

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Abbreviations

ASD:

Amorphous solid dispersion

SDs:

Solid dispersions

DP:

Dipyridamole

PMs:

Physical mixtures

HPMC E5:

Hydroxypropyl methyl cellulose E5

PVP K30:

Poly vinyl pyrrolidne K30

PVPVA 64:

Polyvinylpyrrolidone vinyl acetate

Eudragit® L100:

Eudragit® L100-55

HPMCP:

Hydroxypropyl methyl-cellulose phthalate NF

HPMCAS:

Hydroxypropyl methylcellulose acetate succinate LF

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Funding

The work was supported by the China Postdoctoral Science Foundation (Grant No. 2016M602442), the 111 project (Grant No. B16047), and the Natural Science Fund Project of Guangdong Province (Grant No. 2016A030312013).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People’s Republic of China

    Tingting Peng, Youjun She, Yin Shi, Yao Huang, Boyi Niu, Xuequn Bai, Xin Pan & Chuanbin Wu

  2. Institute for Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, People’s Republic of China

    Chune Zhu

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  1. Tingting Peng
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Correspondence to Chune Zhu or Xin Pan.

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Peng, T., She, Y., Zhu, C. et al. Influence of Polymers on the Physical and Chemical Stability of Spray-dried Amorphous Solid Dispersion: Dipyridamole Degradation Induced by Enteric Polymers. AAPS PharmSciTech 19, 2620–2628 (2018). https://doi.org/10.1208/s12249-018-1082-4

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