Content uniformity is an important aspect of drug product quality. The content uniformity indicates how the active pharmaceutical ingredient is distributed within the entire production batch. It is important to have good content uniformity, to ensure that each patient obtains a dose of the active ingredient which is within the acceptable limits. Content uniformity is often a major concern when the dosage level is low. By selection of the right filler and mixing plan however, even dosage levels of 0.005%w/w can be formulated with a good content uniformity.
Content uniformity is influenced by raw material properties combined with processing steps. It can be improved by improving the effectiveness of dispersion of the active pharmaceutical ingredient.
Content uniformity can be improved by employment of an effective mixing plan to disperse cohesive agglomerates.
- Use layering during addition of API
- Pre-blend API with part of (good flowing) excipients and de-agglomerate (e.g. sieve) before blending in other excipients
- Increase shear during blending
- Select filler-binders with good flow properties and high surface area that help to disperse agglomerates during mixing, like granulated and spray dried lactose
- Reducing the API size results in more particles to disperse
- Segregation can be minimised by the structure of granulated lactose
- Segregation can be minimised by adding a milled or sieved lactose grade with similar particle size as the API
- Segregation can be minimised by use of excipients which have good adherence to the API