Inter- and Intra-Manufacturer Variability in Pharmaceutical Grades and Lots of Xanthan Gum

Abstract

Abstract. A pharmaceutical formulation typically contains one or more excipients in addition to the active pharmaceutical ingredient(s). Though excipients have been considered inert components of a formulation, variability in their properties has been shown to affect the performance of drug dosage forms and delivery systems. This study investigates the inter-and intra-manufacturer variability among different NF grades and lots of xanthan gum made by two manufacturers. As many formulators rely on compendial standards to monitor and control the variability of excipients, this study focuses on the adequacy of the NF specifications, in particular the viscosity specification, to discern the variability in solution properties of different pharmaceutical grades and lots of xanthan gum. All the grades and lots in this study were NF grade materials. Xanthan gum solutions were prepared in accordance with NF test methodology and were rheologically evaluated using a rotational rheometer. Both steady shear measurements and small amplitude oscillatory measurements were carried out on 1% w/w xanthan gum solutions. Results showed significant inter-and intra-manufacturer variability among the NF grades and lots of xanthan gum that was not reflected in the NF viscosity test specifications.

Effect of xanthan gum on processing and cooking quality of nontraditional pasta

“…Results for nitrogen, ash and total glucose contents of XG samples (Table ) were similar to those previously reported (Garcia‐Ochoa et al ., ,b; Thacker et al ., ). These components are present as contaminants in XG.…”

“…NH 4 is a better N‐source for biomass accumulation, while NO 3 is best for XG yield (Rosalam & England, ). Differences in the refining methods (of crude XG) used by manufacturers result in variation in the amount of these contaminants in XG (Thacker et al ., ; El Enshasy et al ., ).…”

“…Thacker et al . () reported significant differences in viscosity parameters among different grades and among different lots of a particular grade of XG manufactured at different times.…”

Biopharmaceutical aspects and implications of excipient variability in drug product performance

“…This minimum of regulatory specifications may suffice for these industries, but pharmaceutical companies have to deal more strictly with excipient variability and be assured that the properties rendering excipients functional are "present" in every batch within appropriate limits. A first issue that arises from current monograph specifications is that they cannot adequately set the appropriate limits in functional specifications ("one-point" limits [25] or a wide range of acceptance values). Without prior mechanistic knowledge of the actual excipient role, variability could be detrimental, even if excipient property values meet monograph specifications [25].…”

Excipient Variability and Its Impact on Dosage Form Functionality

“…The study reported the subsequent impact of these differences on process ability and/or functionality . Thacker et al investigated the intermanufacturer and intramanufacturer variability among the different grades and lots of xanthan gum produced by two manufacturers. A significant intermanufacturer and intramanufacturer variability among the grades and lots of xanthan gum was reported in this study.…”