Dry Powder Inhalers (DPIs) are not just a mode of drug delivery. They are a transformative force in the pharmaceutical industry. Once primarily used for asthma and COPD, they are now opening doors to systemic delivery of biologics, RNA-based therapeutics, vaccines, and even oncology treatments. The advantages they offer over liquid formulations and injectables, including improved stability, faster absorption, and enhanced patient convenience, are reshaping the future of drug delivery.

While dry powder inhaler manufacturing presents unique challenges, these can be overcome with the right approach. Success depends on combining specialized expertise in particle engineering and powder handling with advanced equipment, device integration, and rigorous process control.

By following best practices, innovators can overcome challenges, accelerate development timelines, scale effectively, and maintain regulatory confidence.

Why Dry Powder Inhalers Are Gaining Ground

The advantages of DPIs extend well beyond patient preference. Unlike pressurized metered dose inhalers, DPIs eliminate reliance on high global warming potential (GWP) propellants, aligning with sustainability goals. Compared to nebulizers and soft-mist inhalers, DPIs are easier to manufacture, transport, and use, reducing burden for developers and patients alike.

They also deliver meaningful stability benefits. Reduced water content lowers the risk of chemical degradation and microbial growth, extending shelf life and improving process consistency. By minimizing cold-chain requirements, DPIs simplify global distribution and reduce the need for energy-intensive storage. Just as importantly, passive DPIs eliminate the need for breath coordination, reducing user error and improving real-world adherence.

Formulation Development and Particle Engineering

Every DPI program begins with formulation. Achieving the optimal aerodynamic particle size distribution (APSD) is crucial, as it determines deposition in the respiratory tract and impacts therapeutic outcomes. Dozens of interacting variables, ranging from excipient properties to milling conditions, can influence APSD, underscoring the need for precise control and effective risk management.

Best practices include:

  • Selecting the right particle engineering approach, spray drying as a platform technology, or lyophilization and thin-film freezing (TFF).
  • Conducting early analytical testing and process development to characterize powder properties.
  • Evaluating excipient compatibility while recognizing the regulatory limitations on novel excipients.

Experic specializes in customizing formulations for lactose-based blends and spray-dried dispersions, offering developers a versatile toolkit for solving complex inhalation problems. Most importantly, manufacturability must be balanced with inhalability to ensure programs can move smoothly from clinical stages to market.

Apply Quality by Design (QbD) Principles

A Quality by Design (QbD) framework is essential in DPI manufacturing. By linking critical material attributes and process parameters to finished product properties, QbD ensures reproducibility and robustness while reducing risk. Tools such as Design of Experiments (DOE) and pFMEA enable developers to focus on the variables that matter most, saving time, minimizing costs, and strengthening regulatory submissions.

This approach not only strengthens regulatory submissions but also enhances process robustness and reproducibility. Experic integrates QbD principles into formulation development to optimize inhalation therapies from the outset.

Filling and High-Accuracy Dosing

Dose uniformity and powder flow present some of the most challenging hurdles in inhaler production. Low-dose powders, cohesive APIs, and electrostatic charges can compromise accuracy, requiring precision filling systems to ensure consistency.

Harro Höfliger platforms, from DrumLab (~100 capsules/hour) through Modu-C/MS (~100,000 capsules/hour), enable phase-appropriate scalability while maintaining precision. Advanced engineering ensures even the most challenging powders can be filled accurately, bridging clinical development to commercial supply.

Experic’s cGMP manufacturing services for capsule filling and DPI products are purpose-built to handle even the most challenging powders.

Device and Formulation Integration

Device compatibility is a cornerstone of inhalation development. Capsule-based inhalers remain widely used, but higher-payload, single-dose, and blister-based devices are becoming increasingly important, particularly for programs that require doses of 20-100 mg across multiple inhalations.

Best practices recommend developing the device and formulation in parallel to avoid later bridging studies and accelerate timelines. Formulation must be fit-for-purpose, designed to suit the device’s dispersion mechanism, resistance, and dosing requirements.

By handling capsule, blister, and high-payload formats, Experic ensures seamless integration for inhalation drug-device combinations.

Managing Electrostatics and Low-Humidity Conditions

Powder handling becomes more complex at low relative humidity, when electrostatic charge is more pronounced. Mitigation strategies include equilibrating powders to the manufacturing environment and leveraging equipment features designed for low-humidity operation. While Experic’s cleanrooms are purpose-built for inhalation products, equipment providers also offer static mitigation solutions for ultra-dry environments when required.

Scaling DPI Manufacturing

Scaling DPI manufacturing requires careful planning. Unlike liquids, powders often run more easily at a commercial scale, but they must still be stress-tested at intermediate stages.

Best practices include:

  • Running pilot-scale batches to stress-test processes.
  • Leveraging filling systems that scale by throughput (not speed), ensuring powder dynamics remain consistent.
  • Extending spray dryer run times for clinical batch sizes, while planning for commercialization.

By combining QbD principles with purpose-built equipment, Experic helps innovators scale efficiently while protecting powder integrity and supply chain reliability.

Regulatory and cGMP Compliance

Inhalation therapies are subject to strict regulatory scrutiny due to direct lung delivery. Success depends on rigorous compliance practices, including:

  • Validated cleaning protocols for high-potency powders.
  • Phase-appropriate validation of analytical methods.
  • Comprehensive documentation under cGMP conditions.

While not every test can be run early due to material and budget constraints, best practices recommend conducting as much early characterization as possible to reduce downstream risk. Experic’s cGMP manufacturing expertise ensures DPI products are developed and manufactured to global regulatory standards.

Opportunities Beyond Respiratory

Perhaps the most exciting frontier is using DPIs beyond traditional respiratory medicine. Quick systemic delivery makes them appealing for acute conditions like migraines, where rapid onset is essential. Nasal and pulmonary delivery can also bypass first-pass metabolism, supporting CNS therapies and offering more convenience for patients compared to injections.

Biologics, RNA-based therapeutics, and vaccines are also strong contenders, with dry powders providing better stability and less dependence on cold-chain infrastructure, which is especially important in global public health settings.

Conclusion

Optimizing dry powder inhaler manufacturing requires a balance of science, technology, and scalability. From formulation and particle engineering to device integration, regulatory compliance, and supply chain execution, DPI development is a uniquely complex process, but the therapeutic potential is vast.

Experic combines world-class expertise in dry powder inhalation technologies, state-of-the-art Harro Höfliger systems, and a collaborative approach designed to solve challenges for small- and mid-sized pharmaceutical companies. By partnering with Experic, innovators gain direct access to experts who can accelerate timelines and improve product outcomes.

Partner with Experic today to optimize your dry powder inhaler manufacturing process and bring the next generation of inhalation therapies to patients faster.