Effect of Dispersion Medium on Pharmacokinetic Profile of Rotigotine Crystalline Suspension following Subcutaneous Injection
Rotigotine (RTG) is prescribed as a once-daily transdermal patch for managing early Parkinson’s disease (PD), which presents issues such as skin irritation and poor patient adherence. Therefore, the aims of the present study were to formulate aqueous and oily vehicle-based RTG crystalline suspension...
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MDPI AG
2022-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/12/2630 |
| _version_ | 1797455709704552448 |
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| author | Min Seop Kim Myoung Jin Ho Min Yeong Joung Yong Seok Choi Myung Joo Kang |
| author_facet | Min Seop Kim Myoung Jin Ho Min Yeong Joung Yong Seok Choi Myung Joo Kang |
| author_sort | Min Seop Kim |
| collection | DOAJ |
| description | Rotigotine (RTG) is prescribed as a once-daily transdermal patch for managing early Parkinson’s disease (PD), which presents issues such as skin irritation and poor patient adherence. Therefore, the aims of the present study were to formulate aqueous and oily vehicle-based RTG crystalline suspensions for prolonged delivery and to compare their pharmacokinetic profiles and the local behaviors of RTG crystals. RTG-loaded aqueous (AS) and oil suspensions (OS) were fabricated using bead-milling technology (100 mg/mL as RTG), employing carboxymethyl cellulose and sesame oil as suspending agent and oily vehicle, respectively. RTG AS and OS exhibited comparable physical properties in terms of particle size (about 800–900 nm), crystallinity, and dissolution profile, despite higher drug solubility in OS than AS (19.6 and 0.07 mg/mL, respectively). However, AS and OS exhibited markedly distinctive local distribution and inflammatory responses at the injection site, which further promoted different pharmacokinetic patterns following subcutaneous injection in rats. With OS, no drug aggregates were observed with prolonged persistence of the Sudan III-stained oily vehicle at the injection site. In contrast, with AS injection, drug clusters > 7 mm were formed, followed by an enclosure with macrophages and a fibroblastic band. Accordingly, AS exhibited a protracted pharmacokinetic profile over 3 weeks, with prolonged elimination half-life. The local inflammatory response caused by AS injection was almost alleviated after 3 weeks post-dosing. Based on these findings, we conclude that RTG AS system can be a platform to design sophisticated long-acting delivery systems with extended dosing intervals to manage PD. |
| first_indexed | 2024-03-09T15:58:13Z |
| format | Article |
| id | doaj.art-3ebc1035e08f4492be404dabcf188f89 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T15:58:13Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-3ebc1035e08f4492be404dabcf188f892023-11-24T17:19:15ZengMDPI AGPharmaceutics1999-49232022-11-011412263010.3390/pharmaceutics14122630Effect of Dispersion Medium on Pharmacokinetic Profile of Rotigotine Crystalline Suspension following Subcutaneous InjectionMin Seop Kim0Myoung Jin Ho1Min Yeong Joung2Yong Seok Choi3Myung Joo Kang4College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 330-714, Republic of KoreaCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 330-714, Republic of KoreaCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 330-714, Republic of KoreaCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 330-714, Republic of KoreaCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 330-714, Republic of KoreaRotigotine (RTG) is prescribed as a once-daily transdermal patch for managing early Parkinson’s disease (PD), which presents issues such as skin irritation and poor patient adherence. Therefore, the aims of the present study were to formulate aqueous and oily vehicle-based RTG crystalline suspensions for prolonged delivery and to compare their pharmacokinetic profiles and the local behaviors of RTG crystals. RTG-loaded aqueous (AS) and oil suspensions (OS) were fabricated using bead-milling technology (100 mg/mL as RTG), employing carboxymethyl cellulose and sesame oil as suspending agent and oily vehicle, respectively. RTG AS and OS exhibited comparable physical properties in terms of particle size (about 800–900 nm), crystallinity, and dissolution profile, despite higher drug solubility in OS than AS (19.6 and 0.07 mg/mL, respectively). However, AS and OS exhibited markedly distinctive local distribution and inflammatory responses at the injection site, which further promoted different pharmacokinetic patterns following subcutaneous injection in rats. With OS, no drug aggregates were observed with prolonged persistence of the Sudan III-stained oily vehicle at the injection site. In contrast, with AS injection, drug clusters > 7 mm were formed, followed by an enclosure with macrophages and a fibroblastic band. Accordingly, AS exhibited a protracted pharmacokinetic profile over 3 weeks, with prolonged elimination half-life. The local inflammatory response caused by AS injection was almost alleviated after 3 weeks post-dosing. Based on these findings, we conclude that RTG AS system can be a platform to design sophisticated long-acting delivery systems with extended dosing intervals to manage PD.https://www.mdpi.com/1999-4923/14/12/2630Rotigotineparenteral long-acting deliverycrystalline suspensiondispersion mediumpharmacokineticslocal distribution |
| spellingShingle | Min Seop Kim Myoung Jin Ho Min Yeong Joung Yong Seok Choi Myung Joo Kang Effect of Dispersion Medium on Pharmacokinetic Profile of Rotigotine Crystalline Suspension following Subcutaneous Injection Pharmaceutics Rotigotine parenteral long-acting delivery crystalline suspension dispersion medium pharmacokinetics local distribution |
| title | Effect of Dispersion Medium on Pharmacokinetic Profile of Rotigotine Crystalline Suspension following Subcutaneous Injection |
| title_full | Effect of Dispersion Medium on Pharmacokinetic Profile of Rotigotine Crystalline Suspension following Subcutaneous Injection |
| title_fullStr | Effect of Dispersion Medium on Pharmacokinetic Profile of Rotigotine Crystalline Suspension following Subcutaneous Injection |
| title_full_unstemmed | Effect of Dispersion Medium on Pharmacokinetic Profile of Rotigotine Crystalline Suspension following Subcutaneous Injection |
| title_short | Effect of Dispersion Medium on Pharmacokinetic Profile of Rotigotine Crystalline Suspension following Subcutaneous Injection |
| title_sort | effect of dispersion medium on pharmacokinetic profile of rotigotine crystalline suspension following subcutaneous injection |
| topic | Rotigotine parenteral long-acting delivery crystalline suspension dispersion medium pharmacokinetics local distribution |
| url | https://www.mdpi.com/1999-4923/14/12/2630 |
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