Nanomilling is a cutting-edge pharmaceutical technique used to improve the solubility and bioavailability of poorly water-soluble drugs. At Ascendia Pharmaceutical Solutions, we specialize in advanced nanomilling technologies that transform challenging drug compounds into effective, patient-friendly formulations.
What is Nanomilling?
Nanomilling is a top-down particle size reduction process that involves the mechanical attrition of drug particles to the nanometer scale, typically ranging from 100 to 500 nanometers. This reduction in size dramatically increases the surface area of the particles, thereby enhancing dissolution rates and improving the bioavailability of Biopharmaceutics Classification System (BCS) Class II and IV drugs.
Using wet media milling techniques, nanomilling creates drug nanosuspensions, aqueous dispersions of the active pharmaceutical ingredient (API) stabilized by polymers or surfactants. These nanosuspensions can be incorporated into a wide range of dosage forms, including injectables, oral liquids, and even topical formulations.
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Why Choose Nanomilling?
Poor solubility is a major hurdle in drug development, often resulting in low bioavailability and suboptimal therapeutic outcomes. Nanomilling offers a highly effective solution to this problem, especially when other solubility enhancement techniques, such as salt formation or solid dispersions, fall short.
Benefits of nanomilling include:
- Enhanced dissolution and absorption
- Increased bioavailability
- Reduce or eliminate food effect
- Improved dose uniformity
- Flexible formulation options (oral, injectable, topical)
- Scalability for commercial manufacturing
What Nanomilling Does for Poorly Soluble Drugs
Nanomilling is a proven technique for enhancing the solubility and bioavailability of poorly water-soluble drugs. The process reduces drug particle sizes into the nanometer range, typically between 100 and 500 nanometers. By reducing particles to this size, the surface area increases dramatically, which accelerates dissolution and improves absorption in the body. Also nanomilling increases compound kinetic solubility due to an increase in surface energy; the increased surface area and exposure of new crystalline planes contribute to a higher surface energy density of the material. This is especially critical for BCS Class II and IV compounds, which are often limited by their poor solubility.
How Ascendia Delivers Nanomilling at Scale
Ascendia Pharmaceutical Solutions employs cutting-edge nanomilling technology using equipment from NETZSCH, a globally recognized manufacturer in particle size reduction. NETZSCH mills are installed at multiple scales, from small-volume feasibility work to large-scale GMP production. Ascendia uses NETZSCH DeltaVita® mills, offering end-to-end scalability from early development through commercial manufacturing. Equipment in-house includes small-scale mills for early-stage development and larger systems for late-stage clinical and commercial production. This continuity allows for seamless tech transfer across all phases without the variability that can occur when using different platforms or manufacturers.
Using a consistent mill series ensures reliable scalability. Formulation parameters established during small-scale studies transfer directly to larger systems, reducing variability and timeline risk during scale-up. Parameters such as milling speed, temperature, and media type can be transferred between units with minimal adjustments. This end-to-end equipment strategy lowers the overall cost of development while maintaining quality and compliance.
Meeting cGMP and Sterility Standards for Nanomilling
Ascendia’s nanomilling production takes place in a fully cGMP-compliant cleanroom environment with aseptic processing capabilities. The entire workflow, from material loading to post-milling transfer, occurs in a closed system. This ensures sterility and minimizes cross-contamination risk. The company’s ability to mill APIs under aseptic conditions is critical for injectable nanomilled suspensions and ranks Ascendia high to support sterile product development, especially for parenteral dosage forms.
Formulation Expertise Across Nanotechnology Platforms
Ascendia’s nanomilling service is part of a broader nanotechnology offering that includes three proprietary platforms: NanoSol®, EmulSol®, and LipidSol™. Each platform is designed to address specific formulation challenges:
- NanoSol® delivers stable nanosuspensions using minimal excipients, improving solubility with a small surfactant and polymer footprint.
- EmulSol® uses higher concentrations of emulsifiers to create amorphous solid dispersions and emulsions, targeting highly crystalline APIs that require conversion to the amorphous form for better solubility.
- LipidSol™ offers lipid-based delivery using phospholipids and liposomes, ideal for encapsulating hydrophobic APIs in oncology, antiviral, and vaccine applications.
This tiered approach allows formulation scientists to select the right strategy based on the physicochemical properties of the drug and desired route of administration.
Targeting Long-Acting and Alternative Dosage Forms
Nanomilled APIs can be engineered for various delivery formats beyond oral tablets, including injectable suspensions for intramuscular or subcutaneous delivery. These formats can reduce pill burden and enhance patient compliance in outpatient or at-home care settings. Ascendia's nanomilling capability supports lifecycle management strategies, enabling sponsors to extend product lines with differentiated dosage forms.
Overcoming Scale-Up and Stability Challenges
A common challenge in nanomilling is maintaining particle stability during and after scale-up. Ascendia addresses this through early-stage formulation optimization using appropriate polymers and stabilizers to prevent aggregation and flocculation. The in-house availability of small, mid, and large-scale NETZSCH mills allows for precise control over process conditions during development and commercial manufacturing.
By establishing optimal critical quality attributes (CQAs) and using validated scale-up parameters, Ascendia ensures consistency and reproducibility across batches, key factors for regulatory approval and commercial success.
Ascendia’s End-to-End Nanomilling Capabilities
Ascendia Pharmaceuticals brings deep expertise and full-spectrum capabilities to every stage of nanomilling development. Our state-of-the-art cGMP facilities and experienced formulation scientists are equipped to handle everything from early-stage feasibility to clinical trial material manufacturing and beyond.
Our nanomilling development process includes:
- Pre-formulation screening
- API characterization
- Stabilizer selection and optimization
- Process development and scale-up
- Stability testing
- Final dosage form development
- Scale up and process development
- Manufacturing under cGMP
We utilize advanced wet milling equipment with customizable milling parameters to fine-tune particle size distribution and ensure formulation stability. Our robust quality control systems ensure batch-to-batch consistency and regulatory compliance.
Proven Track Record in Nanomilling
Ascendia has successfully developed multiple nanomilled drug products across a range of therapeutic areas, including oncology, pain management, and infectious diseases. Our customized approach allows us to tailor each formulation to meet the unique challenges and goals of our partners.
With a deep understanding of particle science, excipient compatibility, and process engineering, our team delivers nanomilled products that meet the highest standards of safety, efficacy, and manufacturability.
Partner with Ascendia for Your Nanomilling Needs
Whether you are facing solubility challenges with a new chemical entity or seeking to reformulate an existing product, Ascendia Pharmaceuticals offers the expertise and infrastructure to bring your vision to life. Our commitment to innovation, quality, and speed-to-market makes us the ideal partner for nanomilling drug development. To explore how Ascendia can support your program from preclinical through commercial manufacturing, contact the team today to discuss your project requirements.
Ascendia is ready to help you bring more effective therapies to market.