Chitosan-ethyl cellulose microspheres of domperidone for nasal delivery: Preparation, in-vitro characterization, in-vivo study for pharmacokinetic evaluation and bioavailability enhancement

The strategies to avoid the first-pass metabolism via nose to systemic pathway are been explored to improve the bioavailability of the therapeutic agents. The present study aimed to formulate and evaluate the chitosan (CH)ethylcellulose (EC) based microspheres for the systemic delivery of domperidone (DOM) via the nasal route to improve its bioavailability which is poor (18%) owing to the extensive first-pass metabolism. The microspheres were prepared by the solvent evaporation method and evaluated for certain in-vitro and in-vivo parameters. Invivo study for optimized DOM-Microsphs (F1) formulation was performed on Wistar rats for the evaluation of bioavailability and pharmacokinetic parameters after nasal administration and compared to nasally administered DOM solution (DOM-Sol), and orally administered DOM-Sol & commercially available tablet formulation (ComTab). In-vitro results of optimized formulation (F1) demonstrated that the microspheres were spherical with 21.12 +/- 0.51 mu m particle size, 84.79 +/- 1.39% entrapment efficiency, 50.68 +/- 0.96% drug loading, 81.2 +/- 6.75% drug release in 8 h. DOM loaded microspheres demonstrated 2 fold ex-vivo permeation than that Com-Tab. X-ray diffraction and differential scanning calorimetry spectra do not display the characteristic peak of DOM, thus recommending the encapsulation of the drug in the polymeric core. The relative bioavailability of optimized formulation administered nasally in comparison to DOM-Sol administered orally, DOM Com-Tab administered orally, and DOM-Sol administered nasally was found to be 3.75, 2.61, and 1.77 folds respectively indicating the superiority of developed formulation. The developed microspheres were found to be promising for the bioavailability enhancement of DOM through the nasal route by avoiding its first-pass metabolism. Therefore, the development of microspheres for nasal to systemic route might better choice and a finer option for DOM bioavailability enhancement as well as for avoiding the problem associated with the drug due to irregular drug concentration in the blood with oral administration of the conventional formulation.

Automated summary

The study focused on developing CH-EC based microspheres for nasal delivery of DOM to improve its bioavailability. In vivo experiments showed that the optimized DOM microspheres had higher relative bioavailability compared to nasally administered DOM solution and orally administered DOM-Sol & ComTab.