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Development of favipiravir dry powders for intranasal delivery: An integrated cocrystal and particle engineering approach via spray freeze drying.
Wong, Si Nga; Li, Si; Low, Kam-Hung; Chan, Ho Wan; Zhang, Xinyue; Chow, Stephanie; Hui, Bo; Chow, Philip C Y; Chow, Shing Fung.
Afiliação
  • Wong SN; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, Shatin, Hong Kong Special Administrative Region.
  • Li S; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, Shatin, Hong Kong Special Administrative Region.
  • Low KH; Department of Chemistry, Faculty of Science, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
  • Chan HW; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
  • Zhang X; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
  • Chow S; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
  • Hui B; Department of Mechanical Engineering, Faculty of Engineering, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
  • Chow PCY; Department of Mechanical Engineering, Faculty of Engineering, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
  • Chow SF; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, Shatin, Hong Kong Special Administrative Region. Electronic address: asfchow@h
Int J Pharm ; 653: 123896, 2024 Mar 25.
Article em En | MEDLINE | ID: mdl-38346602
ABSTRACT
The therapeutic potential of pharmaceutical cocrystals in intranasal applications remains largely unexplored despite progressive advancements in cocrystal research. We present the application of spray freeze drying (SFD) in successful fabrication of a favipiravir-pyridinecarboxamide cocrystal nasal powder formulation for potential treatment of broad-spectrum antiviral infections. Preliminary screening via mechanochemistry revealed that favipiravir (FAV) can cocrystallize with isonicotinamide (INA), but not nicotinamide (NCT) and picolinamide (PIC) notwithstanding their structural similarity. The cocrystal formation was characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy, and unit cell determination through Rietveld refinement of powder X-ray analysis. FAV-INA crystalized in a monoclinic space group P21/c with a unit cell volume of 1223.54(3) Å3, accommodating one FAV molecule and one INA molecule in the asymmetric unit. The cocrystal was further reproduced as intranasal dry powders by SFD, of which the morphology, particle size, in vitro drug release, and nasal deposition were assessed. The non-porous flake shaped FAV-INA powders exhibited a mean particle size of 19.79 ± 2.61 µm, rendering its suitability for intranasal delivery. Compared with raw FAV, FAV-INA displayed a 3-fold higher cumulative fraction of drug permeated in Franz diffusion cells at 45 min (p = 0.001). Dose fraction of FAV-INA deposited in the nasal fraction of a customized 3D-printed nasal cast reached over 80 %, whereas the fine particle fraction remained below 6 % at a flow rate of 15 L/min, suggesting high nasal deposition whilst minimal lung deposition. FAV-INA was safe in RPMI 2650 nasal and SH-SY5Y neuroblastoma cells without any in vitro cytotoxicity observed. This study demonstrated that combining the merits of cocrystallization and particle engineering via SFD can propel the development of advanced dry powder formulations for intranasal drug delivery.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazinas / Química Farmacêutica / Amidas / Neuroblastoma Limite: Humans Idioma: En Revista: Int J Pharm Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazinas / Química Farmacêutica / Amidas / Neuroblastoma Limite: Humans Idioma: En Revista: Int J Pharm Ano de publicação: 2024 Tipo de documento: Article