Formulation development and evaluation of nasal in situ gel of promethazine hydrochloride.

Objective: The present work aims to develop mucoadhesive thermosensitive nasal in situ gel for Promethazine hydrochloride using quality by design (QbD) approach. It can reduce nasal mucociliary clearance (MCC) and increase residence of the drug on nasal mucosa. This might increase drug absorption to improve bioavailability of the drug as compared to oral dosage form.

Significance: Promethazine hydrochloride is an antiemetic drug administered by oral, parenteral and rectal routes. These routes have poor patient compliance or low bioavailability. Nasal route is a better alternative as it has large surface area, high drug absorption rate and no first pass effect. Its only limitation is short drug retention time due to MCC. By formulating a mucoadhesive in situ gel, the MCC can be reduced, and drug absorption will be prolonged. Thus, improving bioavailability.

Method: In-situ gel was prepared by cold method having material attributes as concentration of Poloxamer 407 (X₁) as gelling agent and hydroxypropyl methyl cellulose K4M (X₂) as mucoadhesive agent. Critical Quality Attributes (CQA) were gelation temperature, mucoadhesive force and ex-vivo diffusion. Central composite design (CCD) was adopted for optimization.

Result: Optimized formulation satisfied all the CQA significant for nasal administration. Moreover, the formulation was found to be stable in accelerated stability studies for 3 months.

Conclusion: It can be concluded that since the drug can easily permeate through nasal mucosa and can gain access directly in the brain without undergoing first pass metabolism along with increased residence due to mucoadhesion, mucoadhesive in situ gel has potential to increase drug bioavailability.