Preparation and in vitro/in vivo evaluation of a clonidine hydrochloride drug–resin suspension as a sustained-release formulation

The purpose of the present study was to prepare a clonidine hydrochloride (CH) sustained-release suspension.The processes involved in the drug formulation included drug loading, impregnating, and suspension preparation. Clonidine hydrochloride drug-resin complexes (CH-DRC) were prepared using the bath method and the CH-DRC impregnated before the microencapsulation process. Based on the bottom spray fluidized bed coating method, the CH microencapsulated drug-resin complexes (CH-MC) were also prepared using Surelease® (the suspension of ethyl cellulose aqueous dispersion) as the coating material. The effects of coating (process/formulation) on the in vitro release of coating microcapsule were evaluated via single factor investigation and orthogonal design optimization. The CH-MC with optimized formulation was further dispersed in a suitable medium to obtain a sustained-release suspension. Rats were given commercial CH ordinary tablets and the CH sustained-release suspension via intragastric administration. The plasma concentration-time curve and related pharmacokinetic parameters were investigated using the non-compartment model.The Tmax of the CH sustained-release suspension was delayed from 2 h to 5 h compared with the CH ordinary tablets. Similarly, the Cmax was reduced from 32.138 µg·mL-1 to 18.150 µg·mL-1 with the concentration-time curve being more gentle compared with the commercially CH ordinary tablets. After oral administration, the relative bioavailability of CH sustained-release suspension (AUC0-24 of 137.703 µg·h·mL-1) to its CH ordinary tablets (AUC0-24 of 123.337 µg·h·mL-1) was 111.65%.The findings showed that the CH sustained-release suspension for oral administration was successfully formulated.