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Raman Imaging-based Analysis of Drug Powder Dissolution on Calu-3 Cell Monolayers as a Mechanistic Predictor of Nasal
Tomoyuki Furubayashi1,2, Akiko Tanaka3, Ryosuke Tatsuta4
1Laboratory of Pharmaceutical Technology, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-Ku, Kobe, Hyogo, 658-8558, Japan. t-furu@kobepharma-u.ac.jp.
A new dissolution-MRT-BAs (DTB) parameter accurately predicts intranasal powder drug absorption. This Raman spectroscopy method improves nasal drug delivery formulation and bioavailability predictions.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Biophysics
Background:
- Intranasal powder formulations present stability and portability benefits.
- Accurate prediction of intranasal drug absorption is challenging due to limitations in conventional dissolution testing for nasal conditions.
Purpose of the Study:
- To develop a predictive metric for intranasal powder bioavailability.
- To establish an in vitro method for assessing nasal drug dissolution dynamics.
Main Methods:
- Utilized Raman spectroscopy to monitor drug particle dissolution in Calu-3 cell layers.
- Developed the dissolution-MRT-BAs (DTB) parameter by integrating dissolution rate constants, nasal mean residence time (MRT), and bioavailability from solution (BAs).
Main Results:
- Observed varied dissolution profiles for model drugs (rapid, intermediate, limited).
- Demonstrated a strong correlation between the DTB parameter and intranasal powder bioavailability (BAp) (R=0.983, p<0.001).
- Showcased the metric's ability to capture dissolution enhancement by excipients like lactose.
Conclusions:
- The DTB parameter effectively predicts the absorption of intranasal powder formulations.
- Raman spectroscopy offers a quantitative approach for nasal drug delivery formulation development.
- Established a potential in vitro-in vivo correlation for nasal drug delivery systems.
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