The Relationship between the Drug Delivery Properties of a Formulation of Teriparatide Microneedles and the Pharmacokinetic Evaluation of Teriparatide Administration in Rats
- Authors
- Oh, Yu-Jeong; Kang, Nae-Won; Jeong, Hye-Rin; Sohn, Seo-Yeon; Jeon, Yae-Eun; Yu, Na-Young; Hwang, Yura; Kim, Sunkyung; Kim, Dae-Duk; Park, Jung-Hwan
- Issue Date
- May-2022
- Publisher
- SPRINGER/PLENUM PUBLISHERS
- Keywords
- coated microneedles; dissolution rate; diffusion pattern; pharmacokinetics; teriparatide
- Citation
- PHARMACEUTICAL RESEARCH, v.39, no.5, pp.989 - 999
- Journal Title
- PHARMACEUTICAL RESEARCH
- Volume
- 39
- Number
- 5
- Start Page
- 989
- End Page
- 999
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/84536
- DOI
- 10.1007/s11095-022-03254-6
- ISSN
- 0724-8741
- Abstract
- Purpose Teriparatide is an effective drug for the treatment of osteoporosis. This study examines the relationship between the drug delivery properties of the solid formulation with teriparatide and the pharmacokinetic properties of teriparatide in vivo. Methods Teriparatide microneedles with different dissolution rates were prepared using sucrose and carboxymethylcellulose (CMC). There were three aspects of this study: (1) The dissolution rate of teriparatide from both formulations (sucrose and CMC) was measured in vitro. (2) After administration into porcine skin ex vivo, the diffusion rate of FITC-dextran was observed using a confocal microscope. (3) Pharmacokinetic studies were performed in rats and pharmacokinetic data compared with the release rate and the diffusion pattern. Results In the in vitro dissolution experiment, 80% of teriparatide was released within 30 min from the CMC MNs, whereas 80% of teriparatide was released within 10 min from the sucrose MNs. After 30 min, the fluorescence intensity on the surface of the MNs was 40% of the initial intensity for sucrose MNs and 90% for CMC MNs. In the pharmacokinetic study, the C-max values of the CMC and sucrose MNs were 868 pg/mL and 6809 pg/mL, respectively, and the AUC(last) values were 6771 pg*hr/mL for the CMC MNs and 17,171 pg*hr/mL for the sucrose MNs. Conclusions When teriparatide is delivered into the skin using microneedles, the release rate from the solid formulation determines the drug's pharmacokinetic properties. The diffusion pattern of fluorescence into the skin can be used to anticipate the pharmacokinetic properties of the drug.
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