Poorly soluble molecules comprise more than 70 percent of active pharmaceutical ingredients (APIs) entering the drug development pipeline. Thankfully, there are multiple techniques available to increase the solubility and oral bioavailability of poorly soluble APIs, and improve their delivery. When the common technique of micronization is insufficient for APIs exhibiting low solubility, other techniques such as nanomilling are the ideal solution.

Nanomilling is a universal technique capable of resolving issues associated with developing and commercializing drug products with low aqueous solubility. It can be applied to almost any API with water solubility below 200 µg/mL, and is a very adaptable drug delivery platform suitable for oral, injectable, inhalable, and buccal applications, for which fine drug particulates are especially desired in formulations. Benefits of particle size reduction for the parenteral route include small dose volumes (resulting from high drug loading) and avoidance of harsh solvents and/or extreme pH conditions. Advantages for the pulmonary route include the ability to use inhalers intended for solutions, as well as the ability to produce spray-dried powders whose particle sizes are optimized for deep lung delivery.

Other advantages include reduced fed/fasted variability in both liquid and solid dosage forms, faster onset of therapeutic action, low excipient side effects, and the ability to run continuously.

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Figure 1. Media Mill.

Numerous BCS class II and IV APIs have benefitted from nanomilling and gained FDA approvals. It is BCS class II compounds that primarily benefit from a small particle size, since their dissolution step is the rate-determining factor in drug absorption. The BCS classes are depicted in Figure 2.

Figure 2. Diagram depicting BCS classes I-IV.

Experience You Can Trust

Nanomilling is a highly complex process requiring a unique level of CDMO expertise that can only be gained through extensive experience with developing a broad range of APIs.

The experts at Altasciences can take your API from formulation through commercialization. We have the necessary procedures, equipment, and experience to work with any formulation. Our highly skilled teams work with the latest equipment, including the Netzsch DeltaVita 15-300 mill, that can reduce particles to nanometer size with our wet milling options, fill vials in a range of sizes (from 0.3 ml to 500 ml) and package them.

Learn how nanomilling can help resolve your API formulation issues by viewing our latest webinar on the topic.

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