Tags

Type your tag names separated by a space and hit enter

Thermodynamic and kinetic evaluation of the impact of polymer excipients on storage stability of amorphous itraconazole.
Int J Pharm. 2019 Jan 30; 555:394-403.IJ

Abstract

Two pharmaceutical polymers with high glass transition temperatures (Tg > 100 °C), polyvinylpyrrolidone-vinyl acetate copolymer (PVPVA) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), have been assessed for their impact on the storage stability of itraconazole (ITZ) amorphous solid dispersions (ASDs). The results showed that the inhibitory effect of PVPVA on the recrystallization of amorphous ITZ was highly sensitive to surrounding relative humidity (RH), especially at RH above 60%. In contrast, amorphous ITZ in HPMCAS matrix exhibited much stronger resistance to recrystallization even under high RH conditions, reflecting the superior crystallization-inhibitory effect of HPMCAS. While the ITZ loads in the two polymers far exceeded the respective thermodynamic solubility limits, both ASD systems remained physically stable over an extended storage period at RH ≤ 60%. Kinetics rather than thermodynamics dictate the physical stability of ITZ ASDs. Crystallization of ITZ in ASDs appears to involve a complex interplay of multiple factors, including polymer type, glass transition temperatures (Tgs) of drug and polymer, crystallization tendency of amorphous drug, and storage conditions. Specifically, with respect to the impact of polymer type, HPMCAS is particularly effective for maintaining the storage stability of ITZ ASDs, which can be attributed to its higher Tg and lower hydrophilicity.

Authors+Show Affiliations

School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong.School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: thomas.lee@aptorumgroup.com.School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address: albert.chow@aptorumgroup.com.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

30513399

Citation

Zhang, Shuai, et al. "Thermodynamic and Kinetic Evaluation of the Impact of Polymer Excipients On Storage Stability of Amorphous Itraconazole." International Journal of Pharmaceutics, vol. 555, 2019, pp. 394-403.
Zhang S, Lee TWY, Chow AHL. Thermodynamic and kinetic evaluation of the impact of polymer excipients on storage stability of amorphous itraconazole. Int J Pharm. 2019;555:394-403.
Zhang, S., Lee, T. W. Y., & Chow, A. H. L. (2019). Thermodynamic and kinetic evaluation of the impact of polymer excipients on storage stability of amorphous itraconazole. International Journal of Pharmaceutics, 555, 394-403. https://doi.org/10.1016/j.ijpharm.2018.11.063
Zhang S, Lee TWY, Chow AHL. Thermodynamic and Kinetic Evaluation of the Impact of Polymer Excipients On Storage Stability of Amorphous Itraconazole. Int J Pharm. 2019 Jan 30;555:394-403. PubMed PMID: 30513399.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thermodynamic and kinetic evaluation of the impact of polymer excipients on storage stability of amorphous itraconazole. AU - Zhang,Shuai, AU - Lee,Thomas W Y, AU - Chow,Albert H L, Y1 - 2018/12/01/ PY - 2018/08/03/received PY - 2018/11/06/revised PY - 2018/11/22/accepted PY - 2018/12/5/pubmed PY - 2019/4/11/medline PY - 2018/12/5/entrez KW - Amorphous itraconazole KW - Amorphous solid dispersions KW - Crystallization kinetics KW - Phase diagram KW - Polymers KW - Storage stability SP - 394 EP - 403 JF - International journal of pharmaceutics JO - Int J Pharm VL - 555 N2 - Two pharmaceutical polymers with high glass transition temperatures (Tg > 100 °C), polyvinylpyrrolidone-vinyl acetate copolymer (PVPVA) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), have been assessed for their impact on the storage stability of itraconazole (ITZ) amorphous solid dispersions (ASDs). The results showed that the inhibitory effect of PVPVA on the recrystallization of amorphous ITZ was highly sensitive to surrounding relative humidity (RH), especially at RH above 60%. In contrast, amorphous ITZ in HPMCAS matrix exhibited much stronger resistance to recrystallization even under high RH conditions, reflecting the superior crystallization-inhibitory effect of HPMCAS. While the ITZ loads in the two polymers far exceeded the respective thermodynamic solubility limits, both ASD systems remained physically stable over an extended storage period at RH ≤ 60%. Kinetics rather than thermodynamics dictate the physical stability of ITZ ASDs. Crystallization of ITZ in ASDs appears to involve a complex interplay of multiple factors, including polymer type, glass transition temperatures (Tgs) of drug and polymer, crystallization tendency of amorphous drug, and storage conditions. Specifically, with respect to the impact of polymer type, HPMCAS is particularly effective for maintaining the storage stability of ITZ ASDs, which can be attributed to its higher Tg and lower hydrophilicity. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/30513399/Thermodynamic_and_kinetic_evaluation_of_the_impact_of_polymer_excipients_on_storage_stability_of_amorphous_itraconazole_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(18)30889-5 DB - PRIME DP - Unbound Medicine ER -