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 (R(2) = .897) and model predictability (Q(2) = 0.72).

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 (Torque(max)) 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 (V (highP)) and BET surface areas of the MCC grades. Variables that exerted dominant influences on Torque(max) were identified. In particular, the significance of V (highP) in governing wet mass consistency was established. The role of V (highP) 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.

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.

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

PURPOSE: This 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). METHODS: Pellets 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. RESULTS: Crospovidone 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. CONCLUSIONS: Crospovidone 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.

A novel preformulation tool to group microcrystalline celluloses using artificial neural network and data clustering.

PURPOSE: 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 Torque(max) 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.