Construction and in vitro/in vivo evaluation of menantine hydrochloride oral liquid sustained-release drug delivery system

Abstract

Objective

The purpose of the present study was to formulate a menantine hydrochloride (MH) sustained-release suspension.

Methods

Menantine hydrochloride drug resin complex (MH-DRC) was prepared with strong acid cation exchange resin as carrier using water bath method. The MH-DRC was characterized using scanning electron microscopy, X-ray diffraction and infrared spectroscopy. The MH-coated microcapsule (MH-CM) with optimized formulation was further dispersed in a suitable medium to obtain a sustained-release suspension. The rats were given both the MH sustained-release suspension and the commercial MH sustained-release capsule by intragastric administration. The plasma concentration-time curves and related pharmacokinetic parameters were also investigated using a non-atrioventricular model.

Results

MH and ion-exchange resin were ionically bonded. AmberliteIRP®69 had a higher affinity for MH at the initial concentration of 5 mg·mL⁻¹ and a reaction temperature of 25.0 ± 0.5 °C. In vitro drug release profile showed that both the drug resin complex and the coated microcapsules had a certain level of sustained-release effect. The t_1/2 of MH sustained-release suspension was extended from 68.44 h to 72.79 h with the peak blood concentration being decreased to 3.56 μg·mL⁻¹ and the T_max extended to 12 h compared with the commercial MH sustained-release capsule. The concentration-time curve of the self-made MH sustained-release suspension was flattened and the average relative bioavailability (F_r) was 116.65% compared with the commercial MH sustained-release capsules.

Conclusions

The findings showed that the MH sustained-release suspension was successfully formulated with acceptable pharmacokinetic indices for effective treatment of Alzheimer’s disease.

Graphical Abstract

Keywords:

• Ion-exchange resin
• menantine hydrochloride
• suspension
• coating technology
• sustained-release

Disclosure statement

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

Additional information

Funding

The work was supported by 2023 Nantong Jianghai Talent Plan(No 2023A053), 2021 Zhenjiang sixth “169 project” scientific research project, 2021 Jurong Social Development Science&Technology Program (No. ZA42109), 2022 New Drugs and Platform Enhancement Project of the Yangtze Delta Drug Advanced Research Institute. Zhenjiang science and technology project(No SH2020048), China postdoctoral science foundation(No 2020M681532), Jiangsu Planned Projects for Postdoctoral Research Funds(No 2020Z209), Natural Science Research Projects of Universities in Jiangsu Province (No 20KJD350001).