Influence of polymers/excipients on development of agglomerated crystals of secnidazole by crystallo-co-agglomeration technique to improve processability

Abstract

Background: Direct tabletting is a need of Pharmaceutical industries. Poor mechanical properties of drug particles require wet granulation which is uneconomical, laborious, and tedious.

Objective: Objective of this work was to study influence of various polymers/excipients on formation of directly compressible Crystallo-co-agglomerates (CCA) of water soluble drug Secnidazole (hydroxy-2-propyl)-1-methyl-2-nitro-5-imidazole), an antimicrobial agent.

Method: Acetone-petroleum ether system was used to develop CCA of drug in the presence of polymers/excipients. Clarity of the supernatant was considered an endpoint for completion of agglomeration. The prepared CCA were subjected for topographic, micromeritic, mechanical, compressional, and drug release properties.

Results: The process yielded ~92 to 98% wt/wt CCA containing secnidazole with the diameter between 0.2 and 0.7 mm. CCA showed excellent flow, packability, compatibility, and crushing strength. Heckel plot showed lower σ₀ and higher tensile strength with lower elastic recovery (0.55–1.28%) of CCA. Dissolution profile of CCA was improved. Differential scanning calorimetry , fourier transform infra-red, and x-ray diffractometry results showed absence of drug–excipient interaction.

Discussion: Matrix beads were generated with uniform dispersion of crystallized drug. Excellent flow, packability, and compactability were due to sphericity of agglomerates. Higher crushing strength of CCA was an indication of good handling qualities. Lower σ ₀, higher tensile strength, and lower elastic recovery indicated excellent compressibility of agglomerates. Improvement in dissolution profile was due to porous nature of CCA.

Conclusion: Excipients and polymers can play a key role to prepare CCA, an excellent alternative to wet granulation process to prepare particles for direct compression.

Keywords::

• Compressibility
• crushing strength
• heckel
• mechanical property
• kawakita

Acknowledgment

The authors are grateful to UGC, New Delhi for providing financial assistance in this work. The authors are also thankful to Department of Physics, Saurashtra University, Rajkot for providing the facility of pXRD study and Department of Metallurgy, M. S. University for providing the facility of SEM. The authors are grateful to Evonic Degussa Incorporation Pvt. Ltd., Mumbai, India for providing sample of Eudragit polymer as a gift.

Declaration of interest

This work was financially supported by UGC, New Delhi. The authors declared no conflict of interest.