Tags

Type your tag names separated by a space and hit enter

Development and Characterization of Dapsone Cocrystal Prepared by Scalable Production Methods.
AAPS PharmSciTech. 2018 Aug; 19(6):2687-2699.AP

Abstract

In this study, the formation of caffeine/dapsone (CAF/DAP) cocrystals by scalable production methods, such as liquid-assisted grinding (LAG) and spray drying, was investigated in the context of the potential use of processed cocrystal powder for pulmonary delivery. A CAF/DAP cocrystal (1:1 M ratio) was successfully prepared by slow evaporation from both acetone and ethyl acetate. Acetone, ethyl acetate, and ethanol were all successfully used to prepare cocrystals by LAG and spray drying. The powders obtained were characterized by X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), and Fourier transform infrared spectroscopy (FTIR). Laser diffraction analysis indicated a median particle size (D50) for spray-dried powders prepared from acetone, ethanol, and ethyl acetate of 5.4 ± 0.7, 5.2 ± 0.1, and 5.1 ± 0.0 μm respectively, which are appropriate sizes for pulmonary delivery by means of a dry powder inhaler. The solubility of the CAF/DAP cocrystal in phosphate buffer pH 7.4, prepared by spray drying using acetone, was 506.5 ± 31.5 μg/mL, while pure crystalline DAP had a measured solubility of 217.1 ± 7.8 μg/mL. In vitro cytotoxicity studies using Calu-3 cells indicated that the cocrystals were not toxic at concentrations of 0.1 and of 1 mM of DAP, while an in vitro permeability study suggested caffeine may contribute to the permeation of DAP by hindering the efflux effect. The results obtained indicate that the CAF/DAP cocrystal, particularly when prepared by the spray drying method, represents a possible suitable approach for inhalation formulations with applications in pulmonary pathologies.

Authors+Show Affiliations

Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil. School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil.School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil.Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil.Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil.Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil.School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil. lmcabral@pharma.ufrj.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29968042

Citation

do Amaral, Lilian Henriques, et al. "Development and Characterization of Dapsone Cocrystal Prepared By Scalable Production Methods." AAPS PharmSciTech, vol. 19, no. 6, 2018, pp. 2687-2699.
do Amaral LH, do Carmo FA, Amaro MI, et al. Development and Characterization of Dapsone Cocrystal Prepared by Scalable Production Methods. AAPS PharmSciTech. 2018;19(6):2687-2699.
do Amaral, L. H., do Carmo, F. A., Amaro, M. I., de Sousa, V. P., da Silva, L. C. R. P., de Almeida, G. S., Rodrigues, C. R., Healy, A. M., & Cabral, L. M. (2018). Development and Characterization of Dapsone Cocrystal Prepared by Scalable Production Methods. AAPS PharmSciTech, 19(6), 2687-2699. https://doi.org/10.1208/s12249-018-1101-5
do Amaral LH, et al. Development and Characterization of Dapsone Cocrystal Prepared By Scalable Production Methods. AAPS PharmSciTech. 2018;19(6):2687-2699. PubMed PMID: 29968042.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development and Characterization of Dapsone Cocrystal Prepared by Scalable Production Methods. AU - do Amaral,Lilian Henriques, AU - do Carmo,Flavia Almada, AU - Amaro,Maria Inês, AU - de Sousa,Valeria Pereira, AU - da Silva,Luiz Claudio Rodrigues Pereira, AU - de Almeida,Gabriella Silva, AU - Rodrigues,Carlos Rangel, AU - Healy,Anne Marie, AU - Cabral,Lucio Mendes, Y1 - 2018/07/02/ PY - 2018/03/09/received PY - 2018/06/05/accepted PY - 2018/7/4/pubmed PY - 2018/10/20/medline PY - 2018/7/4/entrez KW - cocrystal KW - dapsone KW - dry powder inhaler KW - liquid-assisted grinding KW - spray drying SP - 2687 EP - 2699 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 19 IS - 6 N2 - In this study, the formation of caffeine/dapsone (CAF/DAP) cocrystals by scalable production methods, such as liquid-assisted grinding (LAG) and spray drying, was investigated in the context of the potential use of processed cocrystal powder for pulmonary delivery. A CAF/DAP cocrystal (1:1 M ratio) was successfully prepared by slow evaporation from both acetone and ethyl acetate. Acetone, ethyl acetate, and ethanol were all successfully used to prepare cocrystals by LAG and spray drying. The powders obtained were characterized by X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), and Fourier transform infrared spectroscopy (FTIR). Laser diffraction analysis indicated a median particle size (D50) for spray-dried powders prepared from acetone, ethanol, and ethyl acetate of 5.4 ± 0.7, 5.2 ± 0.1, and 5.1 ± 0.0 μm respectively, which are appropriate sizes for pulmonary delivery by means of a dry powder inhaler. The solubility of the CAF/DAP cocrystal in phosphate buffer pH 7.4, prepared by spray drying using acetone, was 506.5 ± 31.5 μg/mL, while pure crystalline DAP had a measured solubility of 217.1 ± 7.8 μg/mL. In vitro cytotoxicity studies using Calu-3 cells indicated that the cocrystals were not toxic at concentrations of 0.1 and of 1 mM of DAP, while an in vitro permeability study suggested caffeine may contribute to the permeation of DAP by hindering the efflux effect. The results obtained indicate that the CAF/DAP cocrystal, particularly when prepared by the spray drying method, represents a possible suitable approach for inhalation formulations with applications in pulmonary pathologies. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/29968042/Development_and_Characterization_of_Dapsone_Cocrystal_Prepared_by_Scalable_Production_Methods_ L2 - https://dx.doi.org/10.1208/s12249-018-1101-5 DB - PRIME DP - Unbound Medicine ER -