Josephine L. P. Soh

Functionality of cross-linked polyvinylpyrrolidone as a spheronization aid: a promising alternative to microcrystalline cellulose.

PurposeThis work seeks to explore and demonstrate the functionality of cross-linked polyvinylpyrrolidone (crospovidone) as a spheronization aid and a promising alternative to microcrystalline cellulose (MCC).MethodsPellets were prepared with various grades of crospovidone using both small- and large-scale extrusion–spheronization. A Box-Behnken experimental design was employed to elucidate the effects of operating variables on the quality of the pellets. Size and shape analyses of these pellets were conducted and compared to those prepared using MCC.ResultsCrospovidone was believed to behave like a liquid repository in its interaction with water during extrusion–spheronization, although its binding ability was weaker than that of MCC. Spherical pellets of narrow size distribution could be made from the finer crospovidone grades with different lactose grades. However, crospovidone-based formulations required higher water levels than weight-equivalent MCC-based formulations. Crospovidone pellets were of equivalent quality to those prepared with MCC, especially in the shape, size, and yield.ConclusionsCrospovidone can be successfully employed as a spheronization aid to produce good pellets without the need of a binder, unlike most of the previously proposed materials. This study exemplified the enormous potential of crospovidone to serve as a competent alternative to MCC in the production of pellets by extrusion–spheronization.

Utility of Multivariate Analysis in Modeling the Effects of Raw Material Properties and Operating Parameters on Granule and Ribbon Properties Prepared in Roller Compaction

This article aimed to model the effects of raw material properties and roller compactor operating parameters (OPs) on the properties of roller compacted ribbons and granules with the aid of principal component analysis (PCA) and partial least squares (PLS) projection. A database of raw material properties was established through extensive physical and mechanical characterization of several microcrystalline cellulose (MCC) and lactose grades and their blends. A design of experiment (DoE) was used for ribbon production. PLS models constructed with only OP-modeled roller compaction (RC) responded poorly. Inclusion of raw material properties markedly improved the goodness of fit (R2 = .897) and model predictability (Q2 = 0.72).

New indices to characterize powder flow based on their avalanching behavior.

Use of powder avalanches in the study of flow properties of pharmaceutical excipients has yet to be popularized even though it is rather simple to use and yields comparatively reliable results. Commonly employed flow assessment methods include compressibility studies and shear cell and repose angle measurements. Though widely accepted, these methods are not without limitations and inadequacies. More often than not, experimental and environmental conditions lead to a considerable amount of variability in the results obtained. The primary objective of this current work is to propose two new indices, avalanche flow index (AFI) and cohesive interaction index (CoI) based on the avalanche flow behaviors of powders. Not only were these two indices able to describe the ease of powder flow but they also provided a simpler means of quantifying the extent of cohesive interactions within the powder mass without elaborate mathematical functions.

Importance of Raw Material Attributes for Modeling Ribbon and Granule Properties in Roller Compaction: Multivariate Analysis on Roll Gap and NIR Spectral Slope as Process Critical Control Parameters

This work is an extension of the earlier work from this laboratory aimed at identifying raw material properties critical to the modeling of granule and ribbon properties as part of the optimization of roller (RC) compaction processes. The utility of roll gap (RG) and near-infrared (NIR) signal, specifically, the spectral slope, as process critical control parameters (PCCPs) was also evaluated. Raw material tabletability, particle size, size distribution span, and tapped density were found to be most important factors for building robust predictive models. RG and NIR spectral slope in combination with RC operating parameters yielded models with good predictability for RC responses. Our results support the suitability of RG and NIR spectral slope as PCCPs in roller compaction, specifically, through ribbon density monitoring.

Importance of Small Pores in Microcrystalline Cellulose for Controlling Water Distribution during Extrusion–Spheronization

The purpose of this research was to investigate the effects of particle size on the wet massing behavior of microcrystalline cellulose (MCC). In this study, a series of six fractionated MCC grades were customized and specially classified to yield different particle size varieties of the standard grade, Comprecel M101. All seven MCC grades were extensively characterized for the physical properties and wet massing behavior using mixer torque rheometry. Effects of MCC physical properties on the maximum torque (Torquemax) were determined using partial least squares (PLS) analysis. Most physical properties varied systematically with particle size and morphological changes. Marked differences were observed in the small pore volumes (VhighP) and BET surface areas of the MCC grades. Variables that exerted dominant influences on Torquemax were identified. In particular, the significance of VhighP in governing wet mass consistency was established. The role of VhighP has not been reported in any study because this small but significant variation is likely to be obliterated or compensated by variation in other physical properties from MCC grades from different suppliers. The findings demonstrated the role of small pores in governing the wet mass consistency of MCC and provide a better understanding of MCC’s superior performance as a spheronization aid by the ability to fulfill the function as a molecular sponge to facilitate pellet formation during wet granulation processes.

A Novel Preformulation Tool to Group Microcrystalline Celluloses Using Artificial Neural Network and Data Clustering

No HeadingPurpose.To group microcrystalline celluloses (MCCs) using a combination of artificial neural network (ANN) and data clustering.Methods.Radial basis function (RBF) network was used to model the torque measurements of the various MCCs. Output from the RBF network was used to group the MCCs using a data clustering technique known as discrete incremental clustering (DIC). Rheological or torque profiles of various MCCs at different combinations of mixing time and water:MCC ratios were obtained using mixer torque rheometry (MTR). Correlation analysis was performed on the derived torque parameter Torquemax and physical properties of the MCCs.Results.Depending on the leniency of the predefined threshold parameters, the 11 MCCs can be assigned into 2 or 3 groups. Grouping results were also able to identify bulk and tapped densities as major factors governing water-MCC interaction. MCCs differed in their water retentive capacities whereby the denser Avicel PH 301 and PH 302 were more sensitive to the added water.Conclusions.An objective grouping of MCCs can be achieved with a combination of ANN and DIC. This aids in the preliminary assessment of new or unknown MCCs. Key properties that control the performance of MCCs in their interactions with water can be discovered.

Distribution of a viscous binder during high shear granulation—Sensitivity to the method of delivery and its impact on product properties

Binder distribution in the powder mass during high shear granulation is especially critical with the use of viscous liquid binders and with short processing times. A viscous liquid binder was delivered into the powder mass at two flow rates using three methods: pouring, pumping and spraying from a pressure pot. Binder content analyses at the scale of individual granules were conducted to investigate the impact of different delivery conditions on the homogeneity of binder distribution. There was clear evidence of non-uniformity of binder content among individual granules across all delivery conditions, particularly for the fast rates of delivery. Poorer reproducibility values of tablet thickness and disintegration time were observed when binder was poured but this may be overcome by pumping or spraying from the pressure pot. Greater homogeneity of binder distribution occurred with the slow rates of delivery and led to the earlier onset of granule growth and a consequent increase in granule size. Larger granule size and lower proportion of fines were in turn associated with increased granule bulk density and improvement of granule flow. In conclusion, delivery of a viscous binder at a slow rate either by pumping or via a pressure pot was most desirable during granulation.

Roller compaction of crude plant material: influence of process variables, polyvinylpyrrolidone, and co-milling.

Roller compaction of a milled botanical (Baphicacanthus cusia) with and without a binder, polyvinylpyrrolidone (PVP) was conducted. Effects of co‐milling on binder function and flowability of the powder blend was also investigated. Flakes were comminuted, and the size and size distribution, friability, Hausner ratio, and Carr index of the granulations were determined. Crude herb should be reduced to a suitable size for it to be successfully roller compacted. Larger‐sized and less friable granules were obtained with decreasing roller speed. Addition of PVP affected the flowability and binding capacity of the herbal powder blend, which influenced size and friability of the granules. Co‐milling of PVP with the herbal powder enhanced the flow of the blends and the effectiveness of the binder, which contributed favorably to the roller‐compacted product. Roller compaction is a convenient and cost‐effective granulating technique suitable for milled botanicals. Co‐milling can be used to improve the properties of roller‐compacted products.

Feasibility of Eliminating Premixing for the Production of Pellets in a Rotary Processor

This current study aims to explore the feasibility of eliminating the premixing step for making pellets in a rotary processor. Microcrystalline cellulose (MCC) and lactose were used as starting materials. They could be loaded into the rotary processor separately using three different loading configurations (Methods I, II, and III) or as MCC:lactose blend, which was prepared in the separate mixer prior to loading (Method IV). Physical properties of the pellets prepared in Methods I–III were evaluated and compared against those prepared using a premixed blend (Method IV). The effects of loading configuration on pellet quality can be assessed by comparing the pellets prepared in Methods I, II, and III. Physical characterization of pellets included mean size, size distribution, oversized fraction, and shape. No significant difference in pellet properties could be attributed to the effect of premixing. Pellet properties were not significantly affected by the different loading configurations either. This study demonstrated that homogeneous powder blends are not required for the production of pellets in rotary processing. The tumbling action of the powders at the start of rotary processing is sufficient to ensure adequate powder mixing. However, it may be judicious to co-feed the different powders to achieve some preliminary mixing during loading under extreme processing conditions.