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Enhanced pulmonary absorption of poorly soluble itraconazole by micronized cocrystal dry powder formulations.
Eur J Pharm Biopharm. 2017 Jun; 115:65-72.EJ

Abstract

Micronized cocrystal powders and amorphous spray-dried formulations were prepared and evaluated in vivo and in vitro as pulmonary absorption enhancement formulations of poorly soluble itraconazole (ITZ). ITZ cocrystals with succinic acid (SA) or l-tartaric acid (TA) with a particle size diameter of <2μm were successfully micronized using the jet-milling system. The cocrystal crystalline morphologies observed using scanning electron microscopy (SEM) suggested particle shapes that differed from those of the crystalline or spray-dried amorphous ITZ. The micronized ITZ cocrystal powders showed better intrinsic dissolution rate (IDR) and pulmonary absorption profile in rats than that of the amorphous spray-dried formulation and crystalline ITZ with comparable particle sizes. Specifically, in rat pharmacokinetic studies following pulmonary administration, micronized ITZ-SA and ITZ-TA cocrystals showed area under the curve from 0 to 8h (AUC0-8h) values approximately 24- and 19-fold higher than those of the crystalline ITZ and 2.0- and 1.6-fold higher than the spray-dried ITZ amorphous values, respectively. The amorphous formulation appeared physically instable during the studies due to rapid crystallization of ITZ, which was its disadvantage compared to the crystalline formulations. Therefore, this study demonstrated that micronized cocrystals are promising formulations for enhancing the pulmonary absorption of poorly soluble compounds.

Authors+Show Affiliations

Takeda Pharmaceutical Company Ltd., Analytical Development, Pharmaceutical Sciences, Kanagawa 251-8555, Japan. Electronic address: masatoshi.karashima@takeda.com.Takeda Pharmaceutical Company Ltd., Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Kanagawa 251-8555, Japan.Takeda Pharmaceutical Company Ltd., Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Kanagawa 251-8555, Japan.Takeda Pharmaceutical Company Ltd., Analytical Development, Pharmaceutical Sciences, Kanagawa 251-8555, Japan.Takeda Pharmaceutical Company Ltd., Analytical Development, Pharmaceutical Sciences, Kanagawa 251-8555, Japan.Takeda Pharmaceutical Company Ltd., Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Kanagawa 251-8555, Japan.Takeda Pharmaceutical Company Ltd., Analytical Development, Pharmaceutical Sciences, Kanagawa 251-8555, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28223260

Citation

Karashima, Masatoshi, et al. "Enhanced Pulmonary Absorption of Poorly Soluble Itraconazole By Micronized Cocrystal Dry Powder Formulations." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 115, 2017, pp. 65-72.
Karashima M, Sano N, Yamamoto S, et al. Enhanced pulmonary absorption of poorly soluble itraconazole by micronized cocrystal dry powder formulations. Eur J Pharm Biopharm. 2017;115:65-72.
Karashima, M., Sano, N., Yamamoto, S., Arai, Y., Yamamoto, K., Amano, N., & Ikeda, Y. (2017). Enhanced pulmonary absorption of poorly soluble itraconazole by micronized cocrystal dry powder formulations. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 115, 65-72. https://doi.org/10.1016/j.ejpb.2017.02.013
Karashima M, et al. Enhanced Pulmonary Absorption of Poorly Soluble Itraconazole By Micronized Cocrystal Dry Powder Formulations. Eur J Pharm Biopharm. 2017;115:65-72. PubMed PMID: 28223260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced pulmonary absorption of poorly soluble itraconazole by micronized cocrystal dry powder formulations. AU - Karashima,Masatoshi, AU - Sano,Noriyasu, AU - Yamamoto,Syunsuke, AU - Arai,Yuta, AU - Yamamoto,Katsuhiko, AU - Amano,Nobuyuki, AU - Ikeda,Yukihiro, Y1 - 2017/02/20/ PY - 2016/10/04/received PY - 2017/01/27/revised PY - 2017/02/16/accepted PY - 2017/2/23/pubmed PY - 2018/2/22/medline PY - 2017/2/23/entrez KW - Amorphous KW - Cocrystals KW - Crystal engineering KW - Dissolution rate KW - Dry powder formulation KW - Itraconazole (PubChem CID: 3793) KW - Micronized particles KW - Pulmonary absorption SP - 65 EP - 72 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 115 N2 - Micronized cocrystal powders and amorphous spray-dried formulations were prepared and evaluated in vivo and in vitro as pulmonary absorption enhancement formulations of poorly soluble itraconazole (ITZ). ITZ cocrystals with succinic acid (SA) or l-tartaric acid (TA) with a particle size diameter of <2μm were successfully micronized using the jet-milling system. The cocrystal crystalline morphologies observed using scanning electron microscopy (SEM) suggested particle shapes that differed from those of the crystalline or spray-dried amorphous ITZ. The micronized ITZ cocrystal powders showed better intrinsic dissolution rate (IDR) and pulmonary absorption profile in rats than that of the amorphous spray-dried formulation and crystalline ITZ with comparable particle sizes. Specifically, in rat pharmacokinetic studies following pulmonary administration, micronized ITZ-SA and ITZ-TA cocrystals showed area under the curve from 0 to 8h (AUC0-8h) values approximately 24- and 19-fold higher than those of the crystalline ITZ and 2.0- and 1.6-fold higher than the spray-dried ITZ amorphous values, respectively. The amorphous formulation appeared physically instable during the studies due to rapid crystallization of ITZ, which was its disadvantage compared to the crystalline formulations. Therefore, this study demonstrated that micronized cocrystals are promising formulations for enhancing the pulmonary absorption of poorly soluble compounds. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/28223260/Enhanced_pulmonary_absorption_of_poorly_soluble_itraconazole_by_micronized_cocrystal_dry_powder_formulations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(16)30644-0 DB - PRIME DP - Unbound Medicine ER -