Microencapsulation of hydroxyzine HCl by thermal phase separation: in vitro release enhancement and in vivo pharmacodynamic evaluation

Abstract

The systemic effect of hydroxyzine hydrochloride following its oral administration or topical application is associated with non compliant anticholinergic effect. Subsequently, the present study aims to prepare microcapsules loaded with hydroxyzine hydrochloride enabling its controlled release into the skin and reducing the side effect of its systemic absorption. The microcapsules were prepared by thermal phase separation method using ethyl cellulose/cyclohexane. Optimization of the formulation parameters was carried out by: (1) varying the type and the concentration of the coacervation inducer with microcapsules prepared with three different core: wall ratios, (2) by using ethyl cellulose with two different viscosities, (3) and by the addition of pore inducers such as pregelatinized starch and sucrose in order to enhance the drug release. Microcapsules of 99% encapsulation efficiency were prepared using 1% w/v polyisobutylene, and 1:0.1 core: wall ratio. The highest percent of drug is released after 9 h from microcapsules prepared using 1:0.1 core :wall ratio. Almost 100% drug was released after 3 h, from the same microcapsules prepared with pregelatinized starch that acts as a core coated with the drug. The pharmacodynamic effect of the chosen preparation was tested on the shaved back of histamine sensitized rabbits. Histopathological studies were driven for the detection of the healing of inflamed tissues.

Keywords::

• Microcapsules
• thermal phase separation
• hydroxyzine HCl
• pore inducer
• ethylcellulose/cyclohexane
• polyisobutylene