Formulation development and evaluation of nasal in situ gel of promethazine hydrochloride- part II: Pharmacokinetic evaluation and bioavailability studies.

Promethazine hydrochloride, a first-generation H1 receptor blocking agent, possesses antimuscarinic, sedative, and serotonin antagonistic properties. It is widely used as an antiemetic for treating nausea and vomiting caused by motion sickness, vertigo, postoperative and drug-induced vomiting, and Meniere's disease. Although extensively absorbed after oral administration, it undergoes significant first-pass metabolism, resulting in poor bioavailability of about 25 %. To overcome this limitation and improve patient compliance, the nasal route was explored owing to its high vascularity, large surface area, and absence of first-pass metabolism. The major drawback of nasal delivery, mucociliary clearance (MCC), was addressed by formulating a thermosensitive mucoadhesive in situ hydrogel, enhancing residence time and bioavailability. The study aimed to evaluate the safety, stability, and bioavailability of the intranasal in situ hydrogel of promethazine hydrochloride. Safety was assessed using freshly excised sheep nasal mucosa, while accelerated stability studies confirmed formulation stability. In vivo studies were performed using New Zealand White rabbits, and pharmacokinetic parameters were calculated by the trapezoidal rule using a validated HPLC method. The optimized formulation exhibited a Cmax of 296.18 ng/ml, Tmax of 1 hour, and bioavailability of 36.42 %, which is 62.58 % higher than after oral administration, indicating intranasal in situ hydrogel as a promising approach for enhancing bioavailability of antiemetic drugs.