Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension

Abstract

Mucoadhesive buccal films can improve drug absorption by prolonging its retention time on the buccal mucosa. The aim of the study was a comparative assessment of the hemodynamic effects and pharmacokinetics of propranolol hydrochloride (PROP) after buccal and oral administration in spontaneously hypertensive rats. Animals were divided into 3 groups: Group I (control) received 0.5 mL of water with a gastric tube, group II received an immediate-release 10 mg PROP tablet via gastric tube, and group III received a mucoadhesive 10 mg PROP buccal film. Systolic (SP) and diastolic blood pressure (DP), and heart rate (SF) were measured in rats, and pharmacokinetic PROP parameters, Cmax, tmax, and AUC0 → 24, were calculated by noncompartmental analysis. Mucoadhesive buccal films showed superior degree of absorption of PROP over immediate-release tablets (AUC0 → 24: 69.64 µgh/ml versus 24.61 µgh/ml). The tmax value was significantly higher in mucoadhesive buccal films, which indicates a prolonged PROP release and longer therapeutic effect (71.19h versus 29.73h). There was no statistically significant difference in Cmax values ​​between groups II and III of rats (4.74 µg ml versus 7.11 µg ml). Mucoadhesive buccal films provide a more pronounced and long-lasting reduction primarily of SF (reduction of 28-51% lasting from 10 minutes to the twelfth hour of testing), but also SP and DP (between 15-30% from the first to the sixth hour of testing) compared to immediate-release tablets. Mucoadhesive buccal films allow bypass/reduction of the extensive hepatic first-pass metabolism, and consequently improve the therapeutic PROP effect.