Effect of Physical Properties and Chemical Substitution of Excipient on Compaction and Disintegration Behavior of Tablet: A Case Study of Low-Substituted Hydroxypropyl Cellulose (L-HPC)

Saurabh M Mishra,Andreas Sauer

doi:10.3390/macromol2010007

Abstract

As final attributes of dosage form largely depend on the properties of excipients used, understanding the effect of physicochemical properties of excipients is important. In the present study, six grades of L-HPC with varying degrees of particle size and hydroxypropyl content and the influence of the grade on compaction as well as disintegration behavior were studied. All grades of L-HPC were compressed at different compression loads to achieve different tablet porosity. Compressibility and compactibility of L-HPC grades were evaluated using a modified Heckel equation and percolation model. Further effects of particle size and hydroxypropyl content of L-HPC on tablet porosity and disintegration time were evaluated using a 32 full-factorial design. From compaction studies, it was found that compressibility of L-HPC largely depends upon the particle size with lower particle size grade showing lower compressibility. Whereas consolidation/bonding behavior of L-HPC is independent of particle size and % hydroxypropyl content. By factorial design, it was found that particle size and % hydroxypropyl content have a significant effect on the disintegration behavior of L-HPC. It was found that smaller particle sizes and higher hydroxypropyl content of L-HPC show longer disintegration time. Thus, careful consideration of excipients selection should be made to achieve desired quality attribute of the product.

Highlights

It was found that particle size and % hydroxypropyl content have a significant effect on the disintegration behavior of Low-substituted hydroxypropyl cellulose (L-HPC)
In the present study, an attempt has been made to understand the effect of different grades of Low-substituted hydroxypropyl cellulose (L-HPC), a multifunctional novel excipient commonly used as a binder and disintegrant on compaction as well as its disintegration behavior [9]
It was found that particle size has a large effect on deformation behavior/compressibility of L-HPC, and LH-31 with smaller particles was found to be less compressible compared to other grades of L-HPC such as LH-21 and LH-11

Summary

Introduction

Pharmaceutical excipients are an inert material with no therapeutic or pharmacological effect. Polymeric excipients differ in their physical properties such as particle size, morphology, polymorphic forms as well as cross-linkages, molecular weights, and molar substitution ratio from different sources or suppliers of these excipients [1]. These excipient variabilities may have large influences on their functionality and performance in the dosage form. It has been reported that the compaction behavior of lactose monohydrate varies with small variations in hydrate form, moisture content, and particle size [7,8] It is important for a formulation scientist to understand that slight variability in different grades of an excipient can cause a larger deviation in the intended use of the same excipients. In the present study, an attempt has been made to understand the effect of different grades of Low-substituted hydroxypropyl cellulose (L-HPC), a multifunctional novel excipient commonly used as a binder and disintegrant on compaction as well as its disintegration behavior [9]

Methods

Results

Conclusion