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

Abstract

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^® (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 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 (AUC_0–24 of 137.703 µg·h·mL⁻¹) to its CH ordinary tablets (AUC_0–24 of 123.337 µg·h·mL⁻¹) was 111.65%.

Conclusions

The findings showed that the CH sustained-release suspension for oral administration was successfully formulated.

Keywords:

• Clonidine hydrochloride
• ion-exchange resin
• fluidized bed
• sustained-release
• suspension

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This manuscript was sponsored by China Postdoctoral Science Foundation [No. 2020M681532] and Jiangsu Planned Projects for Postdoctoral Research Funds [No. 2020Z209].