Inhaled drug delivery is integral in treating a vast array of respiratory diseases. Ensuring effective and efficient drug delivery is crucial for formulators and the patients being administered these medications.
Partnering with a CDMO provides immense resources and technologies that many manufacturers don’t have in-house. Lubrizol Life Science (LLS) Health has created a guide to help you leverage CDMO expertise to achieve optimal outcomes in your drug manufacturing.
An Overview of CDMO Guidance in Inhalation and Aerosol Drug Delivery Projects
Nebulized products routinely face issues with delivery, including delivery time and delivered dose uniformity.
The particle size of some APIs in suspensions for nebulization may be too large to be captured into aerosolized water droplets. As a result, the drug may not be efficiently delivered to the desired destination in your lungs, depending on the targeted region. With some suspensions, including steroids, the particle size is so large that most water droplets contain no API. When particle size is inconsistent, content and dose uniformity suffer, resulting in suboptimal bioavailability and distribution.
Contrast that with a nanoparticulate suspension with each droplet loaded uniformly with nanoparticles of the API. In this case, you can achieve better content uniformity. Nanoparticulate formulations may be formulated to have low viscosity and can be delivered by commercial, off-the-shelf nebulizers and dosing devices. These nanoparticulate suspensions don’t require a specialized device to ensure drug delivery.
As manufacturers create formulations for inhalation and respiratory-aerosol drug delivery, they must consider how partnering with a CDMO helps them deliver effective, efficient, superior products.
Relevance and Importance of Inhalation and Respiratory Aerosol Drug Delivery
Nanoparticulate suspensions provide many advantages for aerosol drug delivery, especially if the API has low-water solubility. As soon as the formulation hits the lung, droplets are dispersed and exposed to API with a much higher surface area, facilitating the dissolution of the API to coat the lung better and improve bioavailability.
Consider traditional nebulizer treatments. If a child is affected with a respiratory disease, they often use a nebulizer to inhale the prescribed drug. In these instances, children exhale most of the aerosol, and those in the room are exposed to the drugs. The efficiency of delivering medicine is low.
But suppose you have a more concentrated delivery system. In that case, you can deliver the required doses in a fraction of the time and have better patient compliance because you reduce the time needed for a patient to sit still while the dose is delivered.
Inhalation and respiratory aerosol drug delivery is an area open for innovation, bringing more concentrated nanoparticulate suspensions into play. These formulations provide exceptional content uniformity, and because they are device-agnostic, they can be used in most, if not all, off-the-shelf delivery devices. The dosage form doesn’t require a specialized device, facilitating the feasibility and evaluation of dosage forms.
Introduction to our CDMO and Its Role in this Field
LLS Health differentiates itself from competing CDMOs with our expertise in nanomilling and any aqueous-based inhalation products requiring sterilization, including sterile nanoparticulate suspension.
Many drugs treating specific respiratory diseases can be efficiently administered through inhalation or respiratory routes of administration, which is where our core technologies come into play. LLS Health offers full-service CDMO services, including complete CMC services and support specifically for sterile solutions and nanoparticulate suspension vital to treating respiratory illnesses.
Understanding Inhalation and Respiratory Aerosol Drug Delivery
Inhalation and respiratory drugs are delivered via liquid or dry powder dosage forms. These drug formulations require an appropriate mean aerodynamic diameter, particle density, and particle shape.
Any aqueous-based suspensions or solutions developed for inhalation will be sterile. Dry powders will minimize dosage, but particle size must be engineered to maximize impact in your lung, depending on the part of your target lung.
A nebulized dosage form is intended for the lungs to minimize systemic absorption. Too large particles will impact when delivered through the nebulizer dosage form via the mouth, impacting the back of the throat or nose and resulting in higher systemic delivery.
If the particle size is too small, the patient breathes the drug in then out, drastically reducing accurate delivery and drug efficacy.
Drug manufacturers aim for a specific mean aerodynamic diameter to ensure optimal drug delivery. LLS Health can hit that target and ensure sterility with our nanomilling capabilities.
Different Types of Inhalation Delivery Systems: Nebulizers, Metered-Dose Inhalers (MDIs), and Dry Powder Inhalers (DPIs)
There are three primary inhalation delivery systems in use, which we will briefly overview below:
- Nebulizers: Typical nebulizers aerosolize a dilute aqueous solution or suspension in a delivery device. The patient inhales the solution, which often takes a long time because the formulation is highly diluted.
- Metered-Dose Inhalers: MDIs hold gases delivered in a single puff through the mouth. These devices are much more efficient than nebulizers but are more complicated because of special gases or pressures. These dosage forms are typically challenging to develop and fill.
- Dry Powder Inhalers: DPIs usually hold a capsule in a specialized dry powder inhaler device. The capsule is punctured, contents are expelled or eliminated, and the patient breathes in the powder. It’s not an aqueous formulation, so it doesn’t have to be sterile, but the manufacturer is tasked with controlling the bioburden.
The Science Behind Aerosol Drug Delivery: How It Works, Its Advantages, and Potential Challenges
As manufacturers create these drug formulations, they must know the exact location they want to target and where they want the drug delivered. Aerosol drug delivery allows for this type of highly specified location targeting.
As a result, aerosol drug delivery can lower systemic exposure. Many inhalation drug formulations are steroids. You want to reduce unnecessary steroid exposure to parts of the body not targeted for delivery. Because more precise targeting is possible with aerosol delivery, this method is viable for drug administration to the lungs.
However, there are challenges with this method, too, primarily physiological obstacles. Problems with using the mouth can result in ineffective delivery. Particle size must be appropriately engineered to ensure complete delivery and coverage.
The Role of CDMOs in Inhalation and Respiratory Aerosol Drug Delivery
Consider this scenario: You’re creating a sterile dosage form. If the API has low aqueous solubility, you want the appropriate dosage forms to target the delivery of water-insoluble APIs. If you have a coarse suspension, you risk clogging the device and poor homogeneity, especially in aerosol delivery. But nanoparticulate suspensions are more similar to molecular solutions: the particles are so small that you won’t clog the devices. Instead, you’ll achieve greatly improved uniformity and more effective administration.
You need the resources, technology, and expertise to execute all development phases appropriately.
At LLS Health, nanomilling is a core competency and a good form factor for inhalation and respiratory drugs. Our CDMO has the infrastructure to develop nanoparticulate suspensions using the appropriate GRAS excipients for delivery via inhalation. We can scale your formulations and identify the sterilization process. LLS Health can make drug products for GLP studies and take clients into GMP production faster than anyone else on the market.
And our repertoire is ever-expanding. We have supported manufacturing proprietary topical ophthalmic delivery devices and drug-device combinations with cartridges for subcutaneous administration. Our CDMO can fill these devices for both R&D and GMP use. And because we can provide services on a low-volume basis, you can go from R&D to GMP smoothly. We can fill various primary packages, which is an advantage to our clients.
Many CDMOs aren’t willing to bend to accommodate unique client needs. But LLS Health knows that by thinking outside the box, we can partner with our clients to create truly remarkable products that change the pharmaceutical market landscape.
Benefits of Collaborating with a CDMO
Many companies don’t have the equipment or expertise to execute the nanomilling of particulates. By collaborating with LLS Health as your CDMO, you gain access to our infrastructure that empowers you to develop formulations quickly. You can leverage the resources and tools we have at our disposal, saving time and money because you don’t have to onboard that technology.
If there are lulls in your program, we can do the initial work, so you don’t have to worry about incurring the technology’s fixed costs. We do the heavy lifting, and our clients have the advantage of partnering with a company with the expertise and resources in place and on-demand to develop their formulations. We bring a level of maturity to these projects that many organizations do not have in-house.
Our CDMO’s Services in Inhalation and Respiratory Aerosol Drug Delivery
LLS Health offers the complete CMC package for inhalation and respiratory drug delivery devices: formulation development, establishing analytical methods, particle size distribution, etc. We can help merge the formulation to the device and conduct ICH-compliant stability studies to ensure your formulation is compatible with a specific device.
Discussion of Our Capabilities in Ensuring Product Quality, Safety, and Efficacy
You can confidently partner with LLS Health, knowing that we boast a proven CDMO success track record.
LLS Health specializes in sterile nanoparticulate suspensions. We offer aseptic high-energy media milling, and we have the required analytical testing to assess the critical quality attributes of the dosage forms.
Additionally, we have a DEA license for all schedules, allowing us to follow the regulations and protocols required for compliance in developing pharmaceutical dosage forms containing controlled substances.
We ensure product quality, safety, and efficacy and have the history to prove it.
The Future of Inhalation and Respiratory Aerosol Drug Delivery and the Role of CDMOs
The inhalation and respiratory aerosol drug delivery field is expanding and evolving daily. The most pressing trends in this industry focus on alternative routes of administration.
These innovations target lung delivery, but this may represent a viable option for a more patient-centric dosage form for other medicines delivered systemically. Targeted delivery results in fewer side effects (because the drug is delivered specifically to the target organ), improved efficacy and bioavailability, and less time required to deliver the desired dose. All the above benefit the patient and should be considered as we explore administration options and delivery.
The Evolving Role of CDMOs in Meeting Industry Advancements and Challenges
CDMOs play an increasingly crucial role in industry advancements and addressing challenges. These partners must have the appropriate skill set and the infrastructure to support the development and GMP production of the required dosage forms. CDMOs help clients access technology more quickly and cost-efficiently than if they attempted to develop these products in-house.
How Our CDMO is Poised to Drive and Respond to These Changes
LLS Health paves the way for sterile formulations and nanomilling within the inhalation and respiratory aerosol drug delivery market. We can develop and fill these formulations into the required devices, maintaining all regulatory compliances and ensuring a safe, effective product promoting patient health.
LLS Health is the only CDMO that offers aseptic high-energy media milling under GMPs. Many water-insoluble API formulations are not amenable to terminal sterilization. If so, we can achieve a sterile nanoparticulate suspension by starting a sterile bulk API and employing a completely aseptic process.
The Importance of Inhalation and Respiratory Aerosol Drug Delivery and the Role of CDMOs
Aerosol drug delivery is a specialized field. You’re targeting the lungs and respiratory system, but for the appropriate indications, executing targeted delivery to the affected organ is the ideal option for drug manufacturers.
If you can create better dosage forms than conventional dilute nebulized solutions, you’ll lessen administration time and increase efficacy, which benefits the patient. It’s a patient-centric delivery system for specific indications involving the respiratory system.
Manufacturers need CDMOs that facilitate effective navigation of the complexities of inhalation drug development. LLS Health provides the full-service support, expertise, technology, and resources you need to execute your projects from start to finish.
Contact our team today to learn how we support inhalation and respiratory drug delivery and the companies behind this vital industry.