The development of a blend-sampling technique to assess the uniformity of a powder mixture

This article discusses the challenges overcome during the development of a blend-sampling technique and the successful validation of the blending oper ation for a tablet dosage form containing 2% active ingredient. Content uni formity results are discussed for three pilot-scale (15-kg) and seven comme rcial-scale (150-kg) batches of tablets. Blend and core content uniformity data from the pilot-scale batches were acceptable. For the initial commerci al-scale batches, although the tablet core content uniformity data were acc eptable, the blend uniformity results were poor. The blend data for these b atches had very high mean values, but acceptable relative standard deviatio ns (RSDs). This suggested that the drug was being preferentially sampled by the thief but in a consistent, reproducible manner. Extensive testing was performed on a commercial-scale development batch to identify potential cau ses of sampling error. The results of this testing helped define the blend- sampling technique and strategy used to validate the mixing operation.