Mucoadhesive chitosan microspheres of carvedilol for nasal administration

Abstract

The aim of the present study was to develop and characterize chitosan mucoadhesive microspheres of carvedilol (CRV) for nasal delivery to improve bioavailability for treatment of hypertension and angina pectoris. The microspheres were prepared by emulsification-cross-linking method and evaluated for size, shape, entrapment efficiency (EE), in vitro mucoadhesion, in vitro drug release, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The mucoadhesive properties were also evaluated by Freundlich and Langmuir adsorption isotherms. In vivo tests were carried out in rabbits. The microspheres were spherical with size of 20–50 µm, which is favorable for intranasal absorption. The EE was observed from 42% to 68% while percentage mucoadhesion was from 74% to 88%. A strong interaction between mucin and chitosan microspheres was detected explaining adsorption with electrostatic interaction. The microspheres released around 75% of drug in 8 h. DSC and XRD studies revealed that CRV was molecularly dispersed. The absorption rate was rapid and the absolute bioavailability was high, 72.29%. The gamma scintigraphy indicated that the microspheres cleared slowly from the nasal cavity. It was concluded that chitosan microspheres could be used to deliver CRV following nasal administration for improving the bioavailability.

Keywords::

• Microspheres
• chitosan
• CRV
• nasal delivery
• pharmacokinetics

Acknowledgements

Financial assistance to Mr. Sanjay B. Patil in terms of Quality Improvement Programme by All India Council for Technical Education, New Delhi, India is duly acknowledged. The authors are thankful to Dr. R. P. Thripathi, Director, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi, for providing necessary facilities to carry out the radiolabeling experiments. Technical assistance during radiolabeling studies by Mrs. Ankur Kaul, INMAS, Delhi is highly acknowledged. The authors are thankful to Miat, Milano, Italy for providing gift sample of monodose powder nasal insufflator.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.