Formulation and Optimisation of Mucoadhesive Nasal Powder of Celecoxib for Management of Pain Associated with Osteoarthritis

Abstract

Purpose

Celecoxib, a COX-2 inhibitor used for osteoarthritis pain, has poor aqueous solubility and limited oral bioavailability. Nasal delivery offers rapid systemic absorption and bypasses first-pass metabolism. This study aimed to develop a mucoadhesive nasal powder of celecoxib using HPβCD and PVA to enhance solubility and systemic delivery for effective osteoarthritis pain management.

Methods

Mucoadhesive nasal powder of celecoxib with hydroxypropyl-β-cyclodextrin (HPβCD) was prepared using the spray drying technique. A central composite design (CCD) was applied to optimize the powder, considering HPβCD (39.32–78.64 mg) and PVA (0.5–1 mg) as independent variables, with response as drug release. The improvement in solubility was evaluated using the flask shake method. In vitro drug release was carried out by using simulated nasal electrolyte solution while drug permeation was performed by using goat nasal mucosa. Mucoadhesivity of powder was evaluated by texture analyser.

Result

Among nine batches, batch B2 (78.64 mg HPβCD and 1 mg PVA) was selected as optimized, which shows 100% drug release within 5 min. The cumulative permeation of clecoxib (B2) was significantly higher (162.4 µg/cm²) compared to pure celecoxib (40.38 µg/cm²), performed till 75 min at pH 6.4 simulated nasal electrolyte solution (SNES) and maintained at 32 ± 2 ͦC with constant stirring at 277 rpm. PVA-containing formulation exhibited enhanced mucoadhesive strength and effective permeation across goat nasal mucosa, which indicated improved potential for intranasal delivery. HPβCD increased the solubility by 5.36-fold at 1:2 ratio of celecoxib: HPβCD and permeability of celecoxib, while PVA provided mucoadhesivity (higher detachment force at 1019.9 mN) as compared to the formulation without PVA, which enhanced the residence time of powder on nasal mucosa, thus, ultimately enhanced the permeability.

Conclusion

HPβCD and PVA synergistically improved solubility, release profile, and nasal permeation of celecoxib, highlighting their potential for enhanced drug delivery systems. Thus, this formulation offered a convenient alternative for patients who have difficulty in swallowing oral dosage forms and provided a faster onset of action through nasal drug delivery.