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Micronization

Micronization

From feasibility to commercial supply, your molecule processed to sub-10-micron precision at every scale your development demands.

Micronization

Micronization is a critical form of particle engineering that acts as the essential bridge where a Drug Substance (API) is modified to meet the requirements of a Drug Product (DP). In pharmaceutical manufacturing, it is defined as the reduction of API particle size to less than 10 microns. This process optimizes a drug's biopharmaceutical profile, specifically its solubility, dissolution rate, and delivery efficiency.

The primary driver for micronization is the enhancement of bioavailability for poorly soluble molecules, often categorized as BCS Class II compounds. According to the Noyes-Whitney equation, the dissolution rate of a solute is directly proportional to its surface area. By breaking the material into smaller fragments, micronization exponentially increases the surface area, allowing the API to dissolve faster and improve overall exposure.


Jet Milling: Mechanism and Control


Jet milling is the conventional standard for pharmaceutical micronization due to its robustness and safety. This technique utilizes fluid energy to achieve comminution through an impact breakage mechanism. Compressed gas (usually air or nitrogen) expands through grinding nozzles, accelerating particles into high-velocity collisions with each other rather than the mill walls. Because the gas expansion causes adiabatic cooling (i.e. Joule–Thomson effect) the process is thermally stable and ideal for thermolabile compounds.

Success depends on the precise control of three operating parameters: material feeding rate, feeding pressure, and grinding pressure. Development typically involves a risk assessment of bulk properties (e.g. morphology, flowability) and a Design of Experiments (DoE) to define the Normal Operating Range (NOR) and design space for the API.

Customers

  • Small biotechs to Big Pharma
  • CDMO’s (API, Dosage Form, Integrated)
  • Functional Excipient Companies

Phases of Development Supported:

  • Lifecycle Presence: From Pre-Clinical to Commercial Phase
  • Fully Equipped from few grams up to metric Ton Batches
  • One Independent R&D Lab and 3 fully inspected GMP Buildings

Types of Molecules

  • Small Molecule APIs and HPAPIs
  • Functional Excipients
  • NCEs, 505b2s, Generics
Micronization

Selecting the Right Jet Mill

The physical characteristics of the drug substance determine the choice of equipment configuration. While the principles of jet milling are consistent, different systems offer specialized advantages.

Spiral Jet Mills +

In spiral jet mills, high-pressure gas (typically 2–10 bar) enters a cylindrical chamber via tangentially distributed nozzles, creating a high-velocity spiral vortex. Raw material is accelerated into this environment through a Venturi pipe, where comminution occurs primarily through intensive particle-on-particle collisions. The process utilizes static classification. centrifugal forces drag larger particles toward the chamber periphery for further grinding, while sufficiently small particles migrate to a central exhaust outlet. This mechanism provides excellent thermal stability due to the Joule–Thomson effect, making it ideal for thermolabile compounds. Process control is achieved by precisely adjusting material feed rates and grinding pressures.

Opposed Jet Mills +

In opposed jet mills, the grinding gas enters the system via three or more coplanar nozzles situated at the bottom of the milling chamber. Raw material is introduced through a double valve system and accelerated to high velocities, facilitating comminution through intensive particle-on-particle collisions. The gas also provides a fluidizing effect, transporting particles to the upper chamber for dynamic classification. Unlike the static system of spiral mills, this configuration utilizes a classifier wheel. By precisely adjusting the speed of this wheel, operators gain superior control over the particle size cut-off: higher speeds result in finer particles.

Loop Mills +

Loop mills are fluid-jet mills engineered to concentrate the particle-on-particle collisions in one area of the milling chamber. They represent a specialized grinding technology characterized by a comminution profile that sits strategically between a mechanical mill and a jet mill. While traditional mechanical mills are used for coarser grinding and standard jet mills for fine micronization, the loop mill provides an intermediate solution for precision fine-grinding requirements. By leveraging fluid energy to facilitate size reduction, this equipment maintains the thermal stability and product purity advantages inherent to fluid-jet technology without the intensive specific energy application required for micron reduction. This makes loop mills an essential tool for engineering tailored particle size distributions for complex pharmaceutical formulations.

Micronization Explained

Micronization Explained

Micronization is the process of breaking down medicine into tiny, microscopic pieces. Think of it like turning a solid crystal into very fine dust. By making these particles extremely small, usually less than 10 microns, the medicine can dissolve much faster and work more effectively in your body. This is usually done using high-speed gas in a machine where the medicine particles crash into each other until they break apart. These tiny pieces are essential for ensuring the body can absorbs the drug properly or that inhaled medicines can reach deep into your lungs.

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