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Anita Kovács, Nikolett Kis, Mária Budai-Szűcs, Attila Gácsi, Erzsébet Csányi, Ildikó Csóka, Szilvia BerkóInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged 6720, HungaryCorrespondence: Szilvia BerkóUniversity of Szeged, Szeged 6720, Hungarytpdel 44/ Tel/Fax +36-62-545-573Email berkosz@pharm.u-szeged.huPurpose: The aim of our research work was to develop dermally applicable, lidocaine hydrochloride (LID-HCl)-containing semisolid in situ film-forming systems (FFSs) using the Quality by Design (QbD) approach to increase drug permeation into the skin.Methods: Silicones were used to improve the properties of formulations and to increase the permeation through the skin. The QbD approach was applied to ensure quality-based development. With initial risk assessment, the critical material attributes (CMAs) and the critical process parameters (CPPs) were identified to ensure the required critical quality attributes (CQAs).Results: During the initial risk assessment, four high-risk CQAs, namely in vitro drug release, in vitro drug permeation, drying properties, and mechanical properties, and three medium-risk CQAs, namely pH, viscosity, and film appearance were identified and investigated. Moreover, four high-risk CMAs were also considered during the formulation: permeation enhancing excipients, drying excipients, film-forming excipients, and emollients. During the experiments, LID-HCl influenced these critical parameters highly, thereby reducing the drying time. The formulation containing 25% silicone showed the best mechanical properties (49 mN skin adhesion, 20.3% film flexibility, 1.27 N film burst strength), which could predict better patient adherence. In addition, in vitro permeation studies showed that formulation containing 50% silicone has the fastest permeation rate. The flux of diffused API was 6.763 μg/cm2/h, which is much higher compared to the silicone-free formulation (1.5734 μg/cm2/h), and it can already be observed in the lower part of the dermis in 0.5 hour.Conclusion: Our results show that LID-HCl has great influence on the critical parameters of FFSs. The silicone content can improve the applicability of formulations and has a favorable effect on the permeation rate of LID-HCl into the skin.Keywords: in situ film-forming system, Quality by Design, formulation excipients, local anaesthesia |
