Development and optimization of levodopa and benzylhydrazine orally disintegrating tablets by direct compression and response surface methodology

Abstract

The number of Parkinson’s disease (PD) patients with the advanced phase and motor fluctuations is increasing. The objective of this study is developing levodopa/benzylhydrazine orally disintegrating tablets (L/B ODTs), which would provide greater convenience and ease of use than conventional tablets for these patients. In the present study, the L/B ODTs were developed successfully with an optimized formulation using response surface methodology (RSM). The direct compression technology was employed for the preparation of L/B ODTs. Considerably shorter disintegration time and faster dissolution profile were obtained under the optimum formulation with microcrystalline cellulose 25.7%, cross-polyvinylpyrrolidone 6.22% and Sodium carboxymethyl starch 5.36%. The content uniformity (%) of levodopa and benzylhydrazine was 50 ± 1.4% and 14.25 ± 0.6%, respectively. Thickness, friability, hardness and wetting time were 2.8 ± 0.05 mm, 0.46 ± 0.21%, 5.42 ± 1.1 kp and 31.2 ± 2.1 s, respectively, and all of data well comply with the General Principles of the Chinese Pharmacopeia. Mannitol of 22% in formulation could bring a pleasant taste: sweet, cool and refreshing. Almost all the volunteers felt that the ODTs had good taste, no roughness, and no gritty feeling, indicating that the ODTs prepared had good palatability, so patients will have good compliance when taking medicine.

Keywords:

• Levodopa
• benzylhydrazine
• orally disintegrating tablets (ODTs)
• direct compression
• response surface methodology

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant numbers 21546004 and 21576145], the Natural Science Foundation of Shandong Province, China [grant number ZR2017MB065] and the Shandong Provincial Key R&D Program [grant numbers 2019GSF107027, 2019GNC106028 and 2019GSF107033].