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

Objective The purpose of the present study was to prepare a clonidine hydrochloride (CH) sustained-release suspension. Methods 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(R) (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. Results The T (max) of the CH sustained-release suspension was delayed from 2 h to 5 h compared with the CH ordinary tablets. Similarly, the C (max) was reduced from 32.138 mu g.mL(-1) to 18.150 mu g.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 (AUC(0-24) of 137.703 mu g.h.mL(-1)) to its CH ordinary tablets (AUC(0-24) of 123.337 mu g.h.mL(-1)) was 111.65%. Conclusions The findings showed that the CH sustained-release suspension for oral administration was successfully formulated.

Automated summary

The study aimed to prepare a clonidine hydrochloride sustained-release suspension. The results showed that the suspension had a delayed Tmax, reduced Cmax, and a gentler concentration-time curve compared to ordinary tablets. The relative bioavailability of the suspension was 111.65% compared to the tablets.