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Fabrication of Spherical and Worm-shaped Micellar Nanocrystals by Combining Electrospray, Self-assembly, and Solvent-based Structure Control

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Spherical crystallization of mebendazole to improve processability.

Smiti Kumar¹, Garima Chawla, Arvind K Bansal

¹Department of Pharmaceutical Technology Formulations, National Institute of Pharmaceutical Education and Research, Nagar, Punjab, India.

Pharmaceutical Development and Technology

|August 23, 2008

Summary

Spherical crystallization improved Mebendazole (MBZ) properties. This technique enhanced flow, density, and compressibility of the poorly soluble drug, reducing processing needs.

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Area of Science:

Pharmaceutical Technology
Materials Science

Background:

Mebendazole (MBZ) is an antihelmentic drug with poor water solubility, flow, and compressibility due to its needle-shaped crystals and electrostatic charge.
Conventional granulation and agglomeration processes are required to improve micromeretic properties of poorly soluble drugs.

Purpose of the Study:

To optimize spherical crystallization of Mebendazole (MBZ) using spherical agglomeration.
To improve the micromeretic properties, flowability, and compressibility of Mebendazole.

Main Methods:

Spherical agglomeration of Mebendazole (MBZ) was performed using various bridging liquids and polymers.
Crystallization conditions including polymer type, concentration, and stirring rate were varied and optimized.
Characterization of crystal habit, aspect ratio, and mechanical properties (elastic:plastic energy ratio) was conducted.

Main Results:

Optimized spherical crystals achieved an aspect ratio of 1-2, a significant improvement from untreated MBZ's value of 12.
The spherical agglomerates retained Mebendazole's Form C and exhibited enhanced flow properties, high bulk density, and improved compressibility.
Lower elastic:plastic energy ratios were observed for crystals formed with Eudragit-S100 and Hydroxypropylcellulose (HPC), indicating superior compressibility.

Conclusions:

Spherical crystallization is an effective technique for improving the micromeretic properties of poorly soluble drugs like Mebendazole.
The optimized process yields spherical crystals with significantly enhanced flowability and compressibility, potentially reducing the need for secondary processing steps.