Pharmaceutical dosage forms blending

The critical unit operations that should be monitored and/or optimized are the reaction and fermentation steps for the purpose of increasing API yield and reducing the residual impurity profile. Other critical unit operations that are especially important to the end user (pharmaceutical dosage form operations) include precipitation or crystallization, milling, sizing, and purification operations, which may affect the physical properties (particle size and shape, bulk powder flow, blend uniformity, and compressibility) of the API. 

In the present work, such a systematic approach to the physical characterization of pharmaceutical solids is outlined. Techniques available for the study of physical properties are classified as being associated with the molecular level (properties associated with individual molecules), the particulate level (properties pertaining to individual solid particles), and the bulk level (properties associated with an ensemble of particulates). Acquisition of this range of physical information yields a total profile of the pharmaceutical solid in question, whether it is an active drug, an excipient, or a blend of these. The development of a total profile is a requirement for successful manufacture of any solid dosage form. 

According to 21CFR 211.110(a), pharmaceutical manufacturers are legally required to demonstrate the adequacy of mixing to ensure uniformity of in-process powder blends and finished dosage units. The uniformity of dose unit is usually a product specification for oral solid dosage forms and is tested to ensure it meets the compendial acceptance criteria. 

Overall, factors that might affect the adsorption of actives on the carrier surface include surface properties, moisture content, the type and particle size/shape of carriers and actives, as well as the mixing ratio of actives and carriers. Pharmaceutical processes (i.e., milling and granulation) could affect the adsorption process by altering carrier and active properties (i.e., surface properties, size, and shape), hence the characteristics of blending and the quality of the final dosage form. 

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