Formulation and Optimization of Cetirizine Orodispersible Films Using Experimental Design Approaches

Introduction: Orodispersible films (ODFs) represent an innovative and patient-friendly dosage form designed to disintegrate rapidly within the oral cavity without requiring water administration. This technology significantly enhances patient compliance, particularly among pediatric and geriatric populations. This study aimed to formulate, evaluate, and optimize an ODF loaded with 10 mg of Cetirizine Dihydrochloride (CTZ-ODF) to achieve rapid disintegration and suitable mechanical robustness. 

Methods: ODFs were manufactured via the solvent casting method. An initial preformulation screening evaluated five hydrophilic film-forming polymers (PVA, HPMC K4M, HPMC E5, HPMC E15, and Gelatin) alongside three superdisintegrants (Crospovidone, Sodium Starch Glycolate [SSG], and Croscarmellose Sodium). Sorbitol was investigated as a plasticizer at concentrations ranging from 0% to 20%. Two in vitro disintegration testing methodologies (Petri dish method vs. Frame-and-Ball method) were critically compared. Subsequently, an I-Optimal Mixture Design (Design-Expert® 13) was implemented to optimize the key components: HPMC E15 (X1), Glycerol (X2), and SSG (X3).

Results: Screening identified HPMC E15 as the optimal polymer, conferring balanced transparency, flexibility, and rapid disintegration capability. The Frame-and-Ball technique demonstrated superior reproducibility and mechanical discrimination compared to the Petri dish method. Statistical optimization yielded a target optimal formulation comprising 45.61% HPMC E15, 11.12% Glycerol, and 3.16% SSG. The optimized CTZ-ODF exhibited an ultrafast disintegration time of 27 seconds, alongside optimal mechanical integrity and physical stability.

Conclusion: Integrating preformulation screening with an I-Optimal design successfully produced a robust, rapidly disintegrating cetirizine oral film. This platform shows strong promise for industrial scale-up in oral fast-dissolving delivery systems.