Compaction and tableting properties of composite particles of microcrystalline cellulose and crospovidone engineered for direct compression

Excipients with improved functionality have continued to be developed by the particle engineering strategy of co-processing. The aim of this study was to evaluate the compaction and tableting properties of composite particles of microcrystalline cellulose (MCC) and crospovidone (CPV) engineered by co-processing.

Results
Heckel analysis of the compaction behavior revealed a decrease in plasticity of co-processed excipient (CPE) when compared to MCC due to an increase in Heckel yield pressure from 144 to 172 MPa. The compressibility-tabletability-compactibility (CTC) profile revealed a decrease in individual parameters for CPE when compared to MCC. CPE was found to be more sensitive to the lubricant effect of sodium stearyl fumarate (SSF) when compared to MCC and less sensitive to magnesium stearate (MST) when compared to MCC. A higher dilution potential was obtained for MCC (60%) compared to 44% for CPE when metronidazole was used as model drug. Tableting properties revealed that metronidazole tablets generated with CPE by direct compression disintegrated within 15 min and gave a rapid drug release when compared to MCC as a direct compression (DC) excipient.

Conclusion
The compaction and tableting properties of CPE were characterized and yielded tablets with better disintegration and drug release profile when compared to MCC. This study, therefore, confirms the suitability of co-processing as a proven strategy in engineering the performance of excipients.

Background
The development of novel excipients by co-processing has witnessed a surge in the last few decades. Co-processing as a particle engineering technique has proven to be a useful strategy in improving the functionality or performance of existing single component excipients like lactose [1], microcrystalline cellulose [2], and starch [3, 4]. Some of the functionality improvements so far recorded with co-processed excipients include enhanced flowability, compressibility, dilution potential, lubricant sensitivity, stability, moisture sensitivity, superdisintegrating ability, etc. These changes have been ascribed to physical modifications in the particle structure of excipients without recourse to their chemical properties. Hence, changes in the functionality of the developed co-processed excipients have been directly linked to changes in their fundamental properties like particle size, shape, and morphology [5].

Many of the co-processed excipients developed so far were designed for use as multifunctional excipients in direct compression formulations because of the growing preference for direct compression as the method of tablet production [6]. An ideal direct compression excipient should be multifunctional in performance, demonstrating sufficient flowability and compressibility as they constitute more than 50% of the tablet formulation and so determine to a large extent the outcome of the formulation. Hence, co-processed excipients designed for direct compression play a crucial role in tablet formation. The method of direct compression involves a two-step process of blending the formulation ingredients and compressing into tablets at suitable compression pressure. It is therefore necessary to evaluate the compaction behavior of co-processed excipients because the compaction behavior determines the tabletability or manufacturability of the formulation [7]. Compaction behavior refers to the mechanical response of a powder to the applied pressure [8].

During compaction, pressure is applied to transform the powder bed into solid compacts of suitable mechanical strength. This is a necessary step in the tablet-making process. Tableting materials under pressure may exhibit the mechanism of plastic deformation, elastic deformation, or fragmentation depending on the particle structure and chemical composition of the material [9]. Materials undergoing plastic deformation promotes the formation of tablets because they increase the bonding area between particles (compressibility) and bonding strength (compactibility) resulting in improved tabletability [10]. Hence, the present study aims to evaluate the compaction and tableting properties of the composite particles of MCC and CPV designed for use as a co-processed multifunctional excipient in direct compression formulations.

Compaction behavior of the co-processed excipient will be characterized using the conventional methods of Heckel and Kawakita analysis. In addition, compressibility-tabletability-compactibility (CTC) profile of the co-processed excipient in comparison to the constituent excipients, MCC, and CPV, will be generated with data obtained from compaction studies. Tablets containing metronidazole as the model drug will be formulated by direct compression. Dilution potential studies will be carried out to determine the drug-loading capacity of the excipient that will yield tablets of sufficient mechanical strength. To the best of our literature review, no such study has been carried out. Continue to read the whole open access publication here

Keywords: Particle engineering, Microcrystalline cellulose (MCC), Prosolv® (PSV), Crospovidone, sodium stearyl fumarate (SSF),  Compaction studies, Tablet, sodium stearyl fumarate (SSF), colloidal silicon dioxide