Optimize Mixing for consistent quality

Crystallization is the quality defining unit operation. For active pharmaceutical ingredients, mixing can impact the PSD, impurity profile and polymorphic form. For intermediates, mixing may affect the batch cycle time due to longer filtration and drying times. Knowledge-based Mixing scale-up to reproduce lab scale mixing at production scale ensures right first-time plant process validation and batch-to-batch consistency.

Pharmaceutical chemistry scale-up is challenging for fast and heterogeneous reactions and when accompanied with undesired side reactions, an improper mixing at plant scale can result in batch failures, increased downstream processing cost and longer batch cycle times (reduced productivity). An in-depth evaluation of mixing parameters is essential to ensure the achievement of lab yield and impurity profile at plant scale.

Fermentation in the pharmaceutical industry is used to cultivate microorganisms for antibiotics, therapeutic proteins, enzymes and insulin. Scalability of such process is highly challenging as many parameters such as pH, dissolved oxygen concentration, dispersion of air bubbles, and shear rate are critical for desired microorganism culture growth and life.

Solid dissolution is an important unit operation during solid-liquid mixing in the pharmaceutical industry. Incomplete dissolution can result in sub-potent/ low quality batches resulting in batch failure. Mixing equipment and mass transfer rates dictate the solid suspension level and the time required for dissolution. An extended dissolution time may increase the potential of microbial contamination.

Uniform blending in pharmaceuticals formulation relies on probes tracking ingredient mixing across blenders, optimizing blend spots by powder order/quantity. Mixing is essential for the preparation of liquid formulations, such as syrups, suspensions, and parenteral solutions and for topical pharmaceutical formulations, including ointments and creams. Proper mixing ensures the uniform distribution of APIs and excipients in liquid pharmaceutical products and semi-solid dosage forms improving dosing accuracy.

Emulsions aid in delivering active ingredients effectively by dispersing small liquid droplets, crucial for optimizing drug delivery efficacy. The mixing impacts droplet size distribution, average drop size, stability and rheological properties of finished formulation. Mixing parameters such as agitator type, pumping capacity and shear rate play crucial role in the scale-up of emulsification process.