Nanoparticle and lipid-based formulations (LNPs) have become essential in modern drug delivery, especially for mRNA vaccines, gene therapy products, and targeted therapeutics. These delivery systems allow sensitive molecules to reach their target safely and efficiently. While lipids and polymers form the structure of these nanoparticles, solvents such as acetone play a key role in their development.
Acetone is widely used in pharmaceutical processing because it is volatile, highly miscible, and easy to remove. In nanoparticle production, acetone supports critical steps such as polymer precipitation, nanoparticle formation, size control, purification, and solvent removal. This article explains how acetone contributes to LNP and nanoparticle manufacturing, why purity matters, and what pharmaceutical companies must consider to ensure safe and compliant use.
Why Acetone Is Used in Nanoparticle and LNP Manufacturing
Acetone has several properties that make it ideal for nanoparticle formulation:
1. It mixes easily with water and organic solvents
2. It has a low boiling point (56°C), enabling easy evaporation
3. It dissolves a wide range of lipids and polymers
4. It supports controlled precipitation
5. It is compatible with scalable processes such as microfluidics
Because of these characteristics, acetone is used at multiple steps during nanoparticle and lipid-based system preparation.
Role of Acetone in Nanoparticle Precipitation
One of the most important uses of acetone in nanoparticle production is solvent displacement or nanoprecipitation. This method is commonly used for polymeric nanoparticles, lipid particles, and hybrid nanocarriers.
How nanoprecipitation works:
1. The polymer or lipid is first dissolved in acetone
2. The acetone solution is added into water under stirring or controlled mixing
3. Acetone diffuses quickly into the aqueous phase
4. The polymer or lipid loses solubility
5. Nanoparticles are formed through rapid precipitation
This technique is valued for its simplicity, scalability, and ability to create uniform particle sizes.
Why acetone is ideal for this step:
1. It dissolves many lipids and polymers used in drug delivery
2. It diffuses quickly into water, helping create smaller and more uniform nanoparticles
3. It supports mild processing conditions without damaging sensitive molecules
4. It can be removed easily after particle formation
Without acetone, many nanoparticle formulations would be more difficult to prepare consistently.
Acetone in Lipid Nanoparticle (LNP) Systems
Although ethanol is more commonly discussed in LNP formation, acetone also plays a functional role in certain lipid-based processes.
Where acetone may be used in LNP workflows:
1. Dissolving specific lipid excipients
2. Preparing polymer-lipid hybrid nanoparticles
3. Supporting precipitation-driven LNP formation
4. Cleaning of microfluidic and mixing equipment
5. Preparing lipid films or pre-mixes
Acetone’s high solvency power helps dissolve lipids that may not be completely soluble in ethanol or water alone.
Impact of Acetone on Nanoparticle Size and Stability
Nanoparticle performance depends heavily on achieving consistent particle size and stability. Acetone influences these directly.
Factors affected by acetone:
1. Particle Size Distribution
Fast diffusion of acetone into water helps produce smaller nanoparticles. Slower diffusion can create larger or less uniform particles.
2. Encapsulation Efficiency
Controlled precipitation ensures that active ingredients become trapped inside the developing nanoparticle structure.
3. Surface Properties
Some formulations adjust acetone concentration to fine-tune surface charge or hydrophobicity.
4. Batch-to-Batch Consistency
Because acetone diffuses predictably, it supports reproducible results across multiple production runs.
These benefits make acetone highly useful for research-scale and industrial-scale nanoparticle production.
Purification and Solvent Removal: Why Acetone’s Volatility Matters
After nanoparticles are formed, removing acetone completely is a crucial step. Residual solvents can affect:
1. Drug stability
2. Biocompatibility
3. Regulatory acceptance
4. Safety and toxicity profiles
Because acetone evaporates easily, it is well suited for pharmaceutical workflows.
Common acetone removal techniques:
1. Rotary evaporation
Removes large volumes quickly under reduced pressure.
2. Vacuum drying
Eliminates residual solvent that remains trapped inside particles.
3. Dialysis or ultrafiltration
Effective for sensitive biological formulations.
4. Nitrogen purging
Useful for final drying steps.
The goal is to reduce acetone levels to within regulatory limits, often defined by international pharmacopeias.
Why Purity of Acetone Matters in LNP and Nanoparticle Work
Like methanol and other solvents used in advanced biopharma applications, acetone must meet strict purity specifications.
Key concerns with low-purity acetone:
1. Impurities may react with lipids or polymers
2. Residual contaminants may alter particle stability
3. Toxic by-products can compromise safety
4. Poor-quality acetone affects reproducibility
Using pharmaceutical-grade acetone ensures:
1. Low residue on evaporation
2. Minimal water content
3. No interfering organic impurities
4. Compliance with NF/USP, EP, BP
In the production of nanoparticles and LNPs, purity directly influences both performance and regulatory compliance.
Regulatory and Safety Considerations
Regulatory bodies, including EMA, FDA, and ICH, require strict control of solvents used in pharmaceutical manufacturing. Acetone is classified as a Class 3 solvent, meaning it has lower toxic potential but still requires controlled use and validated removal.
Pharmaceutical manufacturers must ensure:
1. Proper solvent recovery and waste handling
2. Full documentation through Certificates of Analysis
3. Testing for residual solvent content
4. GMP-compliant storage and handling
5. Controlled environmental exposure for operators
These practices align with the solvent control expectations described in other pharmaceutical contexts, such as those referenced for MDC in your supporting file.
The Future of Acetone in Nanoparticle and LNP Technologies
As the world continues to adopt more advanced drug delivery systems, the demand for reliable solvents like acetone will continue to grow. Innovations in:
1. Microfluidic nanoparticle production
2. Hybrid lipid–polymer nanoparticles
3. Scalable continuous manufacturing
4. Precision medicine formulations
…all depend on controlled solvent behaviour and high-purity raw materials.
Acetone will remain a key tool because of its versatility, compatibility with biological systems, and predictable performance.
Conclusion
Acetone plays a central role in nanoparticle and lipid-based formulation processes, from precipitation to final solvent removal. Its ability to dissolve lipids and polymers, drive nanoparticle formation, and evaporate quickly makes it invaluable in modern drug delivery technologies such as LNPs.
Using high-purity acetone ensures consistency, stability, and regulatory compliance — all essential for producing safe and effective nanoparticle-based medicines. Purosolv acetone is engineered to meet these stringent demands, offering tightly controlled impurity profiles, low moisture levels, and reliable batch-to-batch performance suited for advanced pharmaceutical applications. As pharmaceutical science continues to advance, acetone will remain a trusted and indispensable solvent in the development of innovative therapies.
Frequently Asked Questions (FAQs)
1. Why is acetone used in nanoparticle production?
Because it dissolves lipids and polymers, diffuses quickly into water, and supports controlled nanoparticle formation.
2. Is acetone safe for pharmaceutical manufacturing?
Yes, when used under GMP conditions and removed to pharmacopeial limits.
3. Does acetone affect particle size?
Yes. Its diffusion rate directly influences nanoparticle size and uniformity.
4. What happens if residual acetone is not removed?
It may affect stability, safety, and regulatory acceptance.
5. Is pharmaceutical-grade acetone required?
Absolutely. High-purity acetone ensures consistent and safe nanoparticle formulation.