Nanocrystals (NCs) have been widely recognized as an available policy for the formulation of long-acting injections for insoluble drugs. Stabilizers are extremely important for the physical stability of NCs because they can reduce the surface free energy of the system. However, whether stabilizers can affect the in vivo performances of long-acting injectable NCs is unclear. In this study, three celecoxib (CXB) NCs formulated with different stabilizers (PVP K17, TPGS, and F68) were successfully developed by the wet milling method. Among the formulations, CXB-NCs/PVP K17 had a lower dissolution rate. More importantly, CXB-NCs/PVP K17 did not show burst release after intramuscular (i.m.) injection to rats, and it had a strong analgesic effect. These results showed that the stabilizers played a key role in the in vivo behaviors of long-acting injectable NCs. This strongly suggested that the burst release could be avoided by alteration of stabilizers of NCs by i.m. injection.
Keywords: Analgesic effects; Celecoxib; Intramuscular injection; Long-acting; Nanocrystals; Pharmacokinetics; Stabilizers.
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