Development and evaluation of mucoadhesive buccal dosage forms of lidocaine hydrochloride by ex-vivo permeation studies.

Abstract

Intraoral lidocaine formulations are applied in children and adults for pain relief. The potential risks associated with orally administered lidocaine due to accidental ingestions were highlighted in a warning letter by the US Food and Drug Administration (FDA). This increases the urgency for a need of a child-appropriate dosage forms. For risk minimization, a novel buccal composite dosage form was developed consisting of a lidocaine containing minitablet centered on top of a bilayered mucoadhesive buccal film, so called composite. The preparation included direct tableting of minitablets as well as film-casting technique. Within a comparability study, the permeation of this composite was classified against marketed lidocaine gel, a single-layer film, and a minitablet. These ex-vivo permeation studies under physiologically related conditions in combination with LC-MS/MS quantification enabled the evaluation of permeation in clinically relevant short-term application. The composite showed comparable permeation to marketed gel (104.26±30.15µg/cm2 vs 128.17±12.49µg/cm2 cumulative amount of drug) and a higher permeation compared to film (25.84±6.01µg/cm2). Therefore, a controlled drug application can be assumed by the composite, whereby the risk of inadvertent swallowing as well as uncontrolled absorbed amount of drug substance may be substantially minimized.