TY - JOUR

T1 - In vitro and in vivo comparison of microcontainers and microspheres for oral drug delivery

AU - Christfort, Juliane Fjelrad

AU - Strindberg, Sophie

AU - Al-khalili, Shaimaa

AU - Bar-Shalom, Daniel

AU - Boisen, Anja

AU - Nielsen, Line Hagner

AU - Mullertz, Anette

PY - 2021

Y1 - 2021

N2 - Microcontainers, which are microfabricated cylindrical devices with a reservoir function, have shown promise as an oral drug delivery system for small molecular drug compounds. However, they have never been evaluated against a relevant control formulation. In the current study, we prepared microcrystalline cellulose (MCC) microspheres as a control for in vitro and in vivo testing of SU-8 microcontainers as an oral drug delivery system. Both dosage forms were loaded with paracetamol and coated with chitosan or polyethylene glycol (PEG) (12 kDa). These coatings were followed by an additional enteric coating of Eudragit (R) S100. In addition, a control dosage form was coated with Eudragit (R) alone. The dosage forms were evaluated in vitro, in a physiologically relevant two-step model simulating rat gastrointestinal fluids, and in vivo by oral administration to rats. In vitro, the microcontainers coated with PEG/Eudragit (R) resulted in a prolonged release of paracetamol compared to the respective microspheres, which was consistent with in vivo observations of a later time (T-max) for maximum plasma concentration (C-max) for the microcontainers. For microspheres and microcontainers coated with chitosan/Eudragit (R), the time for complete in vitro release of paracetamol was very similar, due to an earlier release from the microcontainers. This trend was supported by very similar T-max values in vivo. The in vitro in vivo relation was confirmed by a linear regression with R-2 = 0.9, when T-max for each dosage form was plotted as a function of time for 90% paracetamol release in vitro. From the in vivo study, the average plasma concentration of paracetamol 120 min after dosing was significantly higher for microcontainers than for microspheres (0.3 +/- 0.1 mu g/mL and 0.1 +/-

AB - Microcontainers, which are microfabricated cylindrical devices with a reservoir function, have shown promise as an oral drug delivery system for small molecular drug compounds. However, they have never been evaluated against a relevant control formulation. In the current study, we prepared microcrystalline cellulose (MCC) microspheres as a control for in vitro and in vivo testing of SU-8 microcontainers as an oral drug delivery system. Both dosage forms were loaded with paracetamol and coated with chitosan or polyethylene glycol (PEG) (12 kDa). These coatings were followed by an additional enteric coating of Eudragit (R) S100. In addition, a control dosage form was coated with Eudragit (R) alone. The dosage forms were evaluated in vitro, in a physiologically relevant two-step model simulating rat gastrointestinal fluids, and in vivo by oral administration to rats. In vitro, the microcontainers coated with PEG/Eudragit (R) resulted in a prolonged release of paracetamol compared to the respective microspheres, which was consistent with in vivo observations of a later time (T-max) for maximum plasma concentration (C-max) for the microcontainers. For microspheres and microcontainers coated with chitosan/Eudragit (R), the time for complete in vitro release of paracetamol was very similar, due to an earlier release from the microcontainers. This trend was supported by very similar T-max values in vivo. The in vitro in vivo relation was confirmed by a linear regression with R-2 = 0.9, when T-max for each dosage form was plotted as a function of time for 90% paracetamol release in vitro. From the in vivo study, the average plasma concentration of paracetamol 120 min after dosing was significantly higher for microcontainers than for microspheres (0.3 +/- 0.1 mu g/mL and 0.1 +/-

KW - Microdevices

KW - In vitro in vivo relation

KW - Paracetamol

KW - Eudragit (R) S100

KW - Chitosan

KW - PEG

KW - Mucoadhesive coatings

KW - POLYMERIC MICROCONTAINERS

KW - MICRODEVICES

KW - MUCOADHESIVE

KW - ABSORPTION

KW - CHITOSAN

KW - SYSTEMS

KW - BIOAVAILABILITY

KW - PERMEABILITY

KW - ENHANCEMENT

KW - RETENTION

U2 - 10.1016/j.ijpharm.2021.120516

DO - 10.1016/j.ijpharm.2021.120516

M3 - Journal article

C2 - 33775722

VL - 600

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 120516

ER -