Preparation and evaluation of spray-dried mucoadhesive microspheres for intranasal delivery of prochlorperazine using factorial design

Abstract

The purpose of present research work was to develop spray-dried mucoadhesive microspheres of prochlorperazine (PCPZ) for intranasal administration with an aim to avoid first-pass metabolism and to improve therapeutic effectiveness. A 23 factorial design was employed with amount of polymer, feed flow rate and volume of gluteraldehyde as independent variables while particle size of the microspheres and percentage drug entrapment efficiency as dependent variables.The microspheres were evaluated for drug loading, surface morphology, degree of swelling, in-vitro mucoadhesion, drug release, histopathology and stability studies. Particle size of all batches was found to be in the range of 7.32–15.67 μm. The percentage entrapment efficiency was found to be in the range between 84.90 and 96.21. In-vitro mucoadhesion was performed by adhesion number using goat nasal mucosa and was observed in a range from 76.25 to 87.72. The optimum formulation was selected based on the criteria of attaining the minimum value of particle size with substantial entrapment efficiency. Scanning electron microscopy analysis of the microspheres revealed that the microspheres were nearly smooth and spherical. In-vitro diffusion studies showed non-Fickian drug release.The Fourier transform infrared spectrophotometer spectra revealed no interaction between drug and excipients. Optimum formulation was found to be nonirritant in histopathology study carried out on goat nasal mucosa. The prepared microspheres were found to be stable over a period of 3 months even after stored at 40°C. In conclusion, PCPZ loaded mucoadhesive chitosan microspheres were reported for the first time, being suitable for intranasal delivery for the treatment of nausea and vomiting.

Key words: Chitosan, factorial design, nasal drug delivery, prochlorperazine, spray drying