Study of mucoadhesive microsphere of pirfenidone for nasal drug delivery

Vrushali Kashikar, Shashikant Dhole, Ujawala Kandekar, Prachi Khose


The present research work involves formulation development and evaluation of nasal mucoadhesive microsphere in view
to, improve bioavailability and reduce dosing regimen. Microspheres were prepared by spray drying and cross-linking
method using chitosan and HPMC K4M, using 32 central composite design. Microspheres were evaluated for particle
size, drug content, swelling ability, and percentage yield. Compatibility was checked by doing Fourier transform infrared
spectroscopy and Differential scanning calorimetry study. The polymorphism and particle shape were studied by X-ray
diffraction and scanning electron microscopy. The average particle size of spray-dried and cross-linked formulations were
found in the range between 20-50 μm and 30-60 μm with percent mucoadhesion in the range of 80%-90% and 60-70%,
respectively. In vitro drug release was found to be proportional to drug to polymer ratio. In vitro drug release for optimized
formulation, that is, (F1), for spray-drying method and cross-linking method was found to be 88.73% and 70.93% at the
end of 6 h, respectively. Release of drug from microspheres followed non-Fickian diffusion kinetics. Ex vivo studies were
performed with sheep nasal mucosa for mucoadhesion, histopathological study, and drug permeation. The histopathological study indicates nonirritant nature of microsphere. The microspheres were found to be stable at accelerated storage conditions for 1 month, as per International Conference of Harmonisation guidelines.

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