Integration of lornoxicam nanocrystals into hydroxypropyl methylcellulose-based sustained release matrix to form a novel biphasic release system
, Yen Dong Thi Hoang, , , , , , Apr-2022, In: International Journal of Biological Macromolecules, 209, 2022, p. 441-451
Overview
Abstract:
The study aims to (a) enhance the solubility of a poorly soluble drug by optimization of nanocrystal formulation
using the top-down approach and (b) modify the release profile of this drug, which exhibits a short elimination
half-life, by the integration of a fast-release phase containing the optimized nanocrystals and a sustained-release
phase in a compression-coated tablet. Nanocrystals of the model drug (lornoxicam; LNX) was prepared by
simultaneous application of jet-milling and ball-milling techniques. Investigation of the precipitation inhibition
capacity, thermal property, and interaction of different polymers with the drug revealed polyvinyl pyrrolidone
K30 (PVP) as the most effective stabilizer for nanocrystals. The immediate-release layer containing the optimized
nanocrystals (size of 279.5 ± 11.25 nm and polydispersity index of 0.204 ± 0.01) was then compressed on a
zero-order sustained-release matrix core using different derivatives of hydroxypropyl methylcellulose (HPMC).
Application of the Design of Experiment approach (DoE) was applied to optimize the formulation of tablet.
Analysis of drug concentration in dog plasma by liquid chromatography-tandem mass spectrometry demonstrated
an improvement in the release behavior of LNX from the optimal compression-coated tablet integrating a
HPMC-based sustained release matrix core and a PVP-stabilized lornoxicam nanocrystals coating layer compared
to the reference product.
Keyword(s): Nanocrystal Biphasic release tablet Lornoxicam Design of experiment Pharmacokinetic
| Pages (from-to) | 441-451 |
| Journal | International Journal of Biological Macromolecules |
| Volume | 209 |
| Issue number | 2022 |
| Publication status | Published - Apr-2022 |
| ISBN | 0141-8130 |