Optimization of Clausena anisata leaf extract lozenges as smoking cessation aid: Quality by Design approach, trial-scale production at manufacturing site, and stability evaluation.

Abstract

Objective: The objective of this study was to develop and optimize Clausena anisata leaf extract (CLE) lozenges, a smoking cessation aid, using a Quality by Design (QbD) approach.

Significance: Optimized CLE lozenges offer a scalable, stable herbal smoking-cessation formulation.

Methods: The quality target product profile (QTPP) was defined, critical quality attributes (CQAs) were identified, and an initial risk assessment was performed. The formulation development of CLE lozenges was designed using a Box-Behnken design, incorporating three factors: compression force, microcrystalline cellulose content, and sodium starch glycolate content.

Results: The results indicated that the optimal formulation contained 10% microcrystalline cellulose and 2% sodium starch glycolate, with a compression force of 2000 psi, yielding desirable physical properties, including hardness of 4-6 kgf, friability ≤1%, and disintegration time ≤30 min. This formulation was subsequently scaled up for trial production at a manufacturing site. The trial batch exhibited slight variations in some physical properties but remained within the defined design space. Moreover, the nitrate content and assay results between the laboratory-scale and trial-scale batches were comparable. The trial-scale batch completely dissolved within 1 h. Stability studies demonstrated that the lozenges were more stable when stored in aluminum foil bags with a heat seal than in polyethylene terephthalate (PET) bottles under both 30 °C/75% RH and 40 °C/75% RH conditions for six months.

Conclusions: This study successfully developed and optimized CLE lozenges using the QbD approach. The results suggest that this herbal product can be further scaled up to pilot and production levels for potential use as a smoking cessation aid.