Non-invasive fast-acting lidocaine HCl lozenges for ventricular Arrhythmia: Formulation, optimization, and in vivo pharmacodynamic study

Ventricular arrhythmia is a severe, life-threatening condition that demands immediate medical intervention. Intravenous (IV) lidocaine hydrochloride (HCl) is widely used for emergency management; however, its invasive administration and requirement for medical supervision limit its practicality. While oral administration is a more patient-friendly alternative, lidocaine HCl exhibits only 35 % oral bioavailability due to extensive hepatic first-pass metabolism, leading to inconsistent systemic drug levels. This study aimed to develop lidocaine HCl hard candy lozenges as a non-invasive, fast-acting alternative that leverages oral mucosal absorption to enhance bioavailability and accelerate onset of action. A Central Composite Design (CCD) was employed to optimize the formulation by evaluating the effects of sucrose (X₁) and HPMC E5 (X₂) on drug release (Y₁) and mouth dissolving time (Y₂). Lozenges were prepared using the heating and congealing technique and were assessed for physical properties, in vitro drug release, and in vivo pharmacodynamics. The optimized formulation demonstrated uniform shape, smooth texture, and high mechanical strength, ensuring ease of handling and patient acceptability. It achieved 97.31 % lidocaine HCl release within 5 min and a mouth dissolution time of 11.27 min, confirming rapid systemic availability. Pharmacodynamic evaluation using a calcium chloride-induced ventricular arrhythmia rat model revealed a significant reduction in arrhythmic episodes, with normalization of cardiac electrical activity within 10 min of administration. The rapid therapeutic response was attributed to the formulation's fast dissolution and efficient mucosal absorption, which bypass first-pass metabolism and mimics the rapid action of IV lidocaine HCl. Thus, lidocaine HCl hard candy lozenges provide a novel, non-invasive alternative for ventricular arrhythmia management, overcoming the limitations of injectable formulations while ensuring patient compliance. Future studies should focus on clinical validation, long-term stability, and expanding applications in emergency cardiac care.