Optimization of Very Low-Dose Formulation of Vitamin D3 with Lyophilizate for Dry Powder Inhalation System by Simple Method Based on Time-of-Flight Theory
It has been previously reported that active vitamin D3 (VD3) is a candidate drug that can repair alveolar damage in chronic obstructive pulmonary disease at a very low dose. We herein report the optimization of a very low-dose formulation of VD3 for dry powder inhalation by a simple method based on...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/13/5/632 |
| _version_ | 1797535841601454080 |
|---|---|
| author | Kahori Miyamoto Misato Yanagisawa Hiroaki Taga Hiromichi Yamaji Tomomi Akita Chikamasa Yamashita |
| author_facet | Kahori Miyamoto Misato Yanagisawa Hiroaki Taga Hiromichi Yamaji Tomomi Akita Chikamasa Yamashita |
| author_sort | Kahori Miyamoto |
| collection | DOAJ |
| description | It has been previously reported that active vitamin D3 (VD3) is a candidate drug that can repair alveolar damage in chronic obstructive pulmonary disease at a very low dose. We herein report the optimization of a very low-dose formulation of VD3 for dry powder inhalation by a simple method based on time-of-flight (TOF) theory. As the preparation content of VD3 is very low, aerodynamic particle size distribution cannot be measured by pharmacopeial methods that require quantification of the main drug. Thus, a simple method based on TOF theory, which can measure aerodynamic particle size distribution without quantification, was used. The optimized formulation for an inhalation system using a lyophilized cake contained phenylalanine as the excipient (VD3 1 μg/vial + phenylalanine 0.3 mg/vial) and showed high performance with fine particle fraction ≤ 3 μm = 47.2 ± 4.4%. The difference between the results of pharmacopeial methods and simple method was examined using the formulation containing 10 µg/vial of VD3 and was within 5.0%. The preparation is expected to efficiently deliver VD3 to the lungs. Our simple method can optimize dry powder inhalation formulations more easily and rapidly even when the content of the main drug in a preparation is very low. |
| first_indexed | 2024-03-10T11:50:06Z |
| format | Article |
| id | doaj.art-5a7a5b3510c24ea29f4cebfda721da7b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T11:50:06Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-5a7a5b3510c24ea29f4cebfda721da7b2023-11-21T17:44:02ZengMDPI AGPharmaceutics1999-49232021-04-0113563210.3390/pharmaceutics13050632Optimization of Very Low-Dose Formulation of Vitamin D3 with Lyophilizate for Dry Powder Inhalation System by Simple Method Based on Time-of-Flight TheoryKahori Miyamoto0Misato Yanagisawa1Hiroaki Taga2Hiromichi Yamaji3Tomomi Akita4Chikamasa Yamashita5Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanDepartment of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanDepartment of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanDepartment of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanDepartment of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanDepartment of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanIt has been previously reported that active vitamin D3 (VD3) is a candidate drug that can repair alveolar damage in chronic obstructive pulmonary disease at a very low dose. We herein report the optimization of a very low-dose formulation of VD3 for dry powder inhalation by a simple method based on time-of-flight (TOF) theory. As the preparation content of VD3 is very low, aerodynamic particle size distribution cannot be measured by pharmacopeial methods that require quantification of the main drug. Thus, a simple method based on TOF theory, which can measure aerodynamic particle size distribution without quantification, was used. The optimized formulation for an inhalation system using a lyophilized cake contained phenylalanine as the excipient (VD3 1 μg/vial + phenylalanine 0.3 mg/vial) and showed high performance with fine particle fraction ≤ 3 μm = 47.2 ± 4.4%. The difference between the results of pharmacopeial methods and simple method was examined using the formulation containing 10 µg/vial of VD3 and was within 5.0%. The preparation is expected to efficiently deliver VD3 to the lungs. Our simple method can optimize dry powder inhalation formulations more easily and rapidly even when the content of the main drug in a preparation is very low.https://www.mdpi.com/1999-4923/13/5/632vitamin D3dry powder inhalationpulmonary administrationtime-of-flight measurement |
| spellingShingle | Kahori Miyamoto Misato Yanagisawa Hiroaki Taga Hiromichi Yamaji Tomomi Akita Chikamasa Yamashita Optimization of Very Low-Dose Formulation of Vitamin D3 with Lyophilizate for Dry Powder Inhalation System by Simple Method Based on Time-of-Flight Theory Pharmaceutics vitamin D3 dry powder inhalation pulmonary administration time-of-flight measurement |
| title | Optimization of Very Low-Dose Formulation of Vitamin D3 with Lyophilizate for Dry Powder Inhalation System by Simple Method Based on Time-of-Flight Theory |
| title_full | Optimization of Very Low-Dose Formulation of Vitamin D3 with Lyophilizate for Dry Powder Inhalation System by Simple Method Based on Time-of-Flight Theory |
| title_fullStr | Optimization of Very Low-Dose Formulation of Vitamin D3 with Lyophilizate for Dry Powder Inhalation System by Simple Method Based on Time-of-Flight Theory |
| title_full_unstemmed | Optimization of Very Low-Dose Formulation of Vitamin D3 with Lyophilizate for Dry Powder Inhalation System by Simple Method Based on Time-of-Flight Theory |
| title_short | Optimization of Very Low-Dose Formulation of Vitamin D3 with Lyophilizate for Dry Powder Inhalation System by Simple Method Based on Time-of-Flight Theory |
| title_sort | optimization of very low dose formulation of vitamin d3 with lyophilizate for dry powder inhalation system by simple method based on time of flight theory |
| topic | vitamin D3 dry powder inhalation pulmonary administration time-of-flight measurement |
| url | https://www.mdpi.com/1999-4923/13/5/632 |
| work_keys_str_mv | AT kahorimiyamoto optimizationofverylowdoseformulationofvitamind3withlyophilizatefordrypowderinhalationsystembysimplemethodbasedontimeofflighttheory AT misatoyanagisawa optimizationofverylowdoseformulationofvitamind3withlyophilizatefordrypowderinhalationsystembysimplemethodbasedontimeofflighttheory AT hiroakitaga optimizationofverylowdoseformulationofvitamind3withlyophilizatefordrypowderinhalationsystembysimplemethodbasedontimeofflighttheory AT hiromichiyamaji optimizationofverylowdoseformulationofvitamind3withlyophilizatefordrypowderinhalationsystembysimplemethodbasedontimeofflighttheory AT tomomiakita optimizationofverylowdoseformulationofvitamind3withlyophilizatefordrypowderinhalationsystembysimplemethodbasedontimeofflighttheory AT chikamasayamashita optimizationofverylowdoseformulationofvitamind3withlyophilizatefordrypowderinhalationsystembysimplemethodbasedontimeofflighttheory |