Multivariate analysis as a method to understand variability in a complex excipient, and its contribution to formulation performance

A key part of the Risk Assessment of excipients is to understand how raw material variability could (or does) contribute to differences in performance of the drug product. Here we demonstrate an approach which achieves the necessary understanding for a complex, functional, excipient. Multivariate analysis (MVA) of the certificates of analysis of an ethylcellulose aqueous dispersion (Surelease) formulation revealed low overall variability of the properties of the systems. Review of the scores plot to highlight batches manufactured using the same ethylcellulose raw material in the formulation, indicated that these batches tend to be more closely related than other randomly selected batches. This variability could result in potential differences in the quality of drug product lots made from these batches. Manufacture of a model drug product from Surelease batches coated using different lots of starting material revealed small differences in the release of a model drug, which could be detected by certain model dependent dissolution modelling techniques, but they were not observed when using model-independent techniques. This illustrates that the techniques are suitable for detecting and understanding excipient variability, but that, in this case, the product was still robust

Lessons from co-development of a Single Vessel Processor: methodologies for managing innovation in customer-supplier networks

This article reports on the development of practical methodologies for managers seeking to deal with pre-competitive co-development of process technology, in networks that bring together customers and suppliers. Eschewing the simplistic notion of a simple linear supply ''chain'', the research focuses on the case of a supply network comprising five firms and a university, examining the ways in which technological innovation was managed within it. Action research was employed to develop two novel applications of theories and practices, operationalising innovation theories and the techniques of sociometry. Finally, we discuss the implications for supply chain managers working in networks

Comparative Evaluation of the Powder and Tableting Properties of Regular and Direct Compression Hypromellose from Different Vendors

Hypromellose, a widely used polymer in the pharmaceutical industry, is available in several grades, depending on the percentage of substitution of the methoxyl and hydroxypropyl groups and molecular weight, and in various functional forms (e.g., suitable for direct compression tableting). These differences can affect their physicomechanical properties, and so this study aims to characterise the particle size and mechanical properties of HPMC K100M polymer grades from four different vendors. Eight polymers (CR and DC grades) were analysed using scanning electron microscopy (SEM) and light microscopy automated image analysis particle characterisation to examine the powder’s particle morphology and particle size distribution. Bulk density, tapped density, and true density of the materials were also analysed. Flow was determined using a shear cell tester. Flat-faced polymer compacts were made at five different compression forces and the mechanical properties of the compacts were evaluated to give an indication of the powder’s capacity to form a tablet with desirable strength under specific pressures. The results indicated that the CR grades of the polymers displayed a smaller particle size and better mechanical properties compared to the DC grade HPMC K100M polymers. The DC grades, however, had better flow properties than their CR counterparts. The results also suggested some similarities and differences between some of the polymers from the different vendors despite the similarity in substitution level, reminding the user that care and consideration should be given when substitution is required

Tribo-electrification of active pharmaceutical ingredients and excipients

Blending of active pharmaceutical ingredient (API) and excipients is a pre-requisite to the dry manufacture of solid dosage forms intended for oral use, whether or not granulation steps are employed prior to compaction. Excipients and API are known to be subject to tribo-electric charging, against each other and the materials in which the blends are manufactured (e.g. stainless steel 316). This study aimed to assess and compare the magnitude of tribo-electric charging of excipients and API using a material-sparing technique. Intra-sample variability in tribo-electric charging was found to be generally low. The results showed that excipients had lower charge levels and smaller variability as compared to the API materials. Some of the APIs tested charged extensively to the levels in excess of ± 150 nC/g. It was also found that the extent of particle adhesion to surfaces of the container walls for charged API was considerably greater compared to the excipients. These results suggest that the extent and variability of tribo-electric charging of APIs is the predominant contributor to variability in electrostatic charge of pharmaceutical blends and to any related formulation issues. It is therefore reasonable to conclude that, to control the electrostatic properties of a formulation, it is a priority to control the particle properties of the API