List of Excipients in Branded Drug BREZTRI

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
AstraZeneca Pharmaceuticals LP	BREZTRI	budesonide, glycopyrrolate, and formoterol fumarate	0310-4616	1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHOCHOLINE	2029-04-27
AstraZeneca Pharmaceuticals LP	BREZTRI	budesonide, glycopyrrolate, and formoterol fumarate	0310-4616	CALCIUM CHLORIDE	2029-04-27
AstraZeneca Pharmaceuticals LP	BREZTRI	budesonide, glycopyrrolate, and formoterol fumarate	0310-4616	NORFLURANE	2029-04-27

BREZTRI Aerosphere Excipient Strategy and Commercial Opportunities

Last updated: August 25, 2026

Breztri Aerosphere is AstraZeneca’s fixed-dose triple inhaled therapy for chronic obstructive pulmonary disease (COPD). Its commercial differentiation depends on a pressurized metered-dose inhaler (pMDI), co-suspension delivery technology, and a formulation containing budesonide, glycopyrrolate, and formoterol fumarate. The strongest excipient opportunities are in propellant transition, phospholipid-based suspension systems, porous particle engineering, device compatibility, and regional manufacturing.

The product is marketed in the United States as Breztri Aerosphere and in several markets as Trixeo Aerosphere. It was approved by the U.S. Food and Drug Administration in July 2020 for the maintenance treatment of airflow obstruction and reduction of exacerbations in patients with COPD. It is not indicated for asthma or acute bronchospasm relief. [1]

What excipients are used in Breztri Aerosphere?

Breztri Aerosphere uses hydrofluoroalkane propellant HFA-134a, also known as 1,1,1,2-tetrafluoroethane, as its principal labeled inactive ingredient. AstraZeneca’s Aerosphere platform also uses a proprietary co-suspension system involving phospholipid-based porous particles that help maintain uniform distribution of micronized drug particles in the propellant. [1,2]

Breztri Aerosphere composition

Component	Role in product	Commercial relevance
Budesonide	Inhaled corticosteroid	Micronized active pharmaceutical ingredient
Glycopyrrolate	Long-acting muscarinic antagonist	Micronized active pharmaceutical ingredient
Formoterol fumarate	Long-acting beta-2 agonist	Micronized active pharmaceutical ingredient
HFA-134a	Propellant	Delivers the suspension from the pMDI
Phospholipid-based porous particles	Suspension and delivery aid in the Aerosphere platform	Supports dose uniformity and drug dispersion
Aluminum canister, metering valve and actuator	Device components	Critical to extractable dose, plume geometry and usability

Breztri’s prescribing information identifies HFA-134a as the inactive ingredient. The detailed Aerosphere formulation platform incorporates porous particles composed of phospholipid materials. AstraZeneca has described the particles as part of a co-suspension delivery system designed to suspend drug crystals and improve dose consistency. [1,2]

The exact grade, particle-size distribution, surface-area profile and manufacturing process for the proprietary porous particles are commercial formulation know-how rather than routine label information.

How does the Breztri excipient system work?

The Aerosphere system separates the functions of suspension stabilization and drug delivery from the active ingredients themselves. Micronized drug crystals are associated with porous particles dispersed in HFA-134a. The porous particles have a low density relative to conventional nonporous excipient particles, which can reduce sedimentation and improve redispersibility.

Co-suspension technology

Traditional pMDI suspensions can experience:

• Sedimentation or creaming;
• Dose variability during storage;
• Poor redispersion after insufficient shaking;
• Drug aggregation;
• Valve and actuator deposition;
• Changes in emitted dose over the product shelf life.

The Aerosphere platform uses phospholipid-based porous particles as a carrier. The carrier is intended to provide a stable surface for the micronized active ingredients and to create a more consistent suspension. This approach may reduce dependence on high concentrations of surfactants or other conventional suspension aids.

For an excipient supplier, the value is not limited to the chemical identity of the phospholipid. The commercial opportunity includes control of:

• Particle morphology;
• Porosity;
• Bulk density;
• Surface-energy characteristics;
• Moisture content;
• Residual solvent levels;
• Aerodynamic behavior;
• Compatibility with HFA propellants;
• Interaction with the metering valve.

These specifications can create meaningful barriers to substitution even where the excipient is not individually patented.

What formulation patents protect Breztri Aerosphere?

Breztri’s principal protection is likely distributed across multiple layers rather than a single active-ingredient patent. Relevant layers include the triple-drug combination, inhaled COPD treatment methods, pMDI compositions, co-suspension particles, particle morphology and manufacturing processes.

Patent protection categories

Protection layer	Potential subject matter	Relevance to excipient strategy
Composition patents	Budesonide, glycopyrrolate and formoterol combinations	Limits direct substitution of the active formulation
Formulation patents	Suspension compositions containing phospholipid porous particles	Protects the delivery architecture
Device patents	Canister, valve and actuator configurations	May restrict device-equivalent products
Method-of-use patents	Maintenance treatment of COPD with triple therapy	Can affect generic labeling and launch strategy
Process patents	Manufacture of porous particles and drug loading	Protects manufacturing know-how
Regional patents	U.S., Europe, Japan and other national rights	Determines geographic freedom to operate

The U.S. Orange Book is the primary source for current listed patents and exclusivity information for Breztri. The FDA approved Breztri under new drug application 212122. The product is a small-molecule inhalation medicine, so biosimilar pathways do not apply. Any competitive entrant would generally pursue an abbreviated new drug application, a 505(b)(2) application, or a full application depending on formulation, device and clinical differences. [1,3]

A prospective generic must address pharmaceutical equivalence, device performance, aerodynamic particle-size distribution, emitted dose, spray pattern, plume geometry and comparative clinical or pharmacodynamic requirements established by FDA guidance. A formulation that changes the excipient system may create regulatory and patent risks even if the three active ingredients remain unchanged. [4]

When does Breztri lose exclusivity?

Breztri’s U.S. market exclusivity is determined by the combination of statutory regulatory exclusivity and listed patent rights. FDA approval occurred on July 24, 2020. The product’s market position is therefore governed primarily by patent expiry and any applicable pediatric exclusivity, not by an extended biologic exclusivity period. [1,3]

Exclusivity timeline

Event	Date or status
U.S. FDA approval	July 24, 2020
Product type	New combination inhalation product
Regulatory pathway for competitors	ANDA, 505(b)(2) or full NDA, depending on product
Biosimilar pathway	Not applicable
Core regulatory exclusivity	Must be confirmed in current FDA exclusivity records
Patent expiry	Depends on the current Orange Book patent list and patent-term adjustments
Generic launch date	Depends on patent challenges, litigation and settlement terms

The critical commercial date is not simply the earliest patent expiration. Inhaled combination products often have several patent families covering formulation, delivery system, device and treatment methods. A noninfringing generic may need to design around more than one claim set, while a Paragraph IV challenger may attempt to invalidate or avoid the relevant patents.

Which companies are challenging Breztri patents?

Public competition around Breztri is likely to develop through ANDA filings and Paragraph IV certifications rather than biosimilar applications. The FDA does not generally disclose all ANDA applicants before approval, and public visibility depends on litigation filings, court dockets and settlement disclosures.

A Paragraph IV certification alleges that an Orange Book-listed patent is invalid, unenforceable or will not be infringed by the proposed generic. If AstraZeneca brings patent litigation within the statutory period, FDA approval of the ANDA can be delayed by a 30-month stay, subject to statutory exceptions and court outcomes. [3]

Generic entry risks

The main entry risks include:

1. Device sameness. A competitor must demonstrate that its actuator, valve and canister deliver comparable doses and aerodynamic performance.

2. Suspension equivalence. The generic may need to reproduce the functional behavior of the phospholipid porous-particle system without copying protected claims.

3. Triple-therapy complexity. The product combines three active ingredients with different physicochemical properties and dose levels.

4. Method-of-use patents. COPD maintenance-treatment claims may complicate labeling strategy, particularly if a generic seeks a carve-out.

5. Manufacturing reproducibility. Small changes in particle morphology or drug loading can alter emitted dose and lung deposition.

For suppliers, these risks increase the value of qualified second sources for excipients, particle intermediates and propellants. They also make regulatory-grade material characterization a competitive advantage.

What excipient opportunities exist for Breztri and competing inhalers?

The largest opportunity is the transition away from high-global-warming-potential propellants. HFA-134a has a global warming potential of approximately 1,300 over a 100-year period. The European Union’s F-gas framework and broader corporate sustainability programs are increasing pressure on inhaler manufacturers to assess lower-impact propellants. [5]

Lower-global-warming-potential propellants

Candidate propellants include:

• HFA-152a, also known as 1,1-difluoroethane;
• HFO-1234ze(E), also known as trans-1,3,3,3-tetrafluoropropene;
• Other emerging low-global-warming-potential hydrofluoroolefins.

A propellant change is not a simple excipient replacement. It can affect:

• Vapor pressure;
• Solubility of phospholipids;
• Suspension stability;
• Valve compatibility;
• Canister pressure;
• Spray force;
• Plume temperature;
• Droplet evaporation;
• Lung deposition;
• Dose uniformity;
• Flammability and transport requirements.

A lower-impact Breztri-type formulation would require reformulation, device reassessment and potentially a new regulatory submission. Suppliers with pharmaceutical-grade HFA-152a or HFO-1234ze, validated filling processes and inhalation toxicology packages have a potential strategic position.

Phospholipid porous particles

Phospholipid carriers are a higher-value opportunity than commodity propellants because they can be differentiated through material performance. Potential supplier offerings include:

• Defined phosphatidylcholine grades;
• Spray-dried porous particles;
• Controlled morphology particles;
• Low-moisture excipient systems;
• Pre-loaded drug-excipient intermediates;
• Particle engineering services;
• Analytical packages for aerodynamic characterization.

A supplier that can produce consistent porous particles at commercial scale may support both originator lifecycle management and generic development.

Device-compatible excipients

Excipients must work with the complete pMDI system. Commercial opportunities include materials that reduce:

• Valve sticking;
• Actuator deposition;
• Drug loss on canister walls;
• Dose drift;
• Aggregation;
• Moisture sensitivity.

The preferred supplier is likely to be one that provides a complete qualification package covering extractables and leachables, inhalation safety, batch consistency, container closure compatibility and long-term stability.

How does Breztri compare with competing triple inhalers?

Breztri competes primarily with Trelegy Ellipta from GSK and other inhaled triple therapies. Breztri is a pMDI, while Trelegy Ellipta is a dry-powder inhaler. The excipient strategy is therefore fundamentally different.

Product	Active ingredients	Device platform	Main excipient issue
Breztri Aerosphere	Budesonide, glycopyrrolate, formoterol fumarate	pMDI	Propellant and co-suspension system
Trelegy Ellipta	Fluticasone furoate, umeclidinium, vilanterol	Dry-powder inhaler	Carrier-based powder flow and dispersion
Trixeo Aerosphere	Budesonide, glycopyrronium, formoterol fumarate	pMDI	Same Aerosphere platform outside the U.S.

Breztri’s pMDI format can be commercially attractive for patients who have difficulty generating the inspiratory flow needed for some dry-powder inhalers. Its dependence on HFA-134a creates a separate environmental and reformulation exposure.

Trelegy’s dry-powder platform creates demand for lactose or other carrier systems, powder engineering and moisture-control technologies. The two products therefore compete clinically but generate different excipient supply chains.

What is the FDA regulatory status of Breztri?

FDA approved Breztri Aerosphere for twice-daily maintenance treatment of COPD. Each actuation delivers 160 micrograms of budesonide, 9 micrograms of glycopyrrolate, and 4.8 micrograms of formoterol fumarate. The product is administered as two inhalations twice daily. [1]

The product is not a rescue inhaler. It is used for maintenance treatment and reduction of COPD exacerbations. FDA labeling also carries class-specific warnings associated with inhaled corticosteroids, long-acting beta agonists and anticholinergic therapy. [1]

For an excipient change, regulatory impact depends on whether the change affects delivered dose, aerodynamic performance, stability, device operation or safety. A change to a nonfunctional processing aid may be manageable through a post-approval supplement. A propellant or porous-particle change is more likely to require extensive comparative data.

What manufacturing and IP barriers affect Breztri suppliers?

The main barriers are process capability and analytical control. The relevant manufacturing steps may include:

1. Production of porous phospholipid particles;
2. Micronization of the three active ingredients;
3. Drug loading onto or association with the carrier particles;
4. Suspension preparation in HFA-134a;
5. Canister filling;
6. Valve crimping and actuator assembly;
7. Stability and dose-uniformity testing.

Critical quality attributes include delivered dose uniformity, aerodynamic particle-size distribution, fine-particle dose, assay, impurity profile, suspension redispersibility, microbial quality, moisture and extractables.

Intellectual-property barriers may protect particle structure, drug-carrier relationships, suspension ratios, manufacturing conditions and device integration. A supplier can reduce freedom-to-operate risk by offering independently developed particle architectures, alternative phospholipid compositions or noninfringing manufacturing routes.

What commercial opportunities exist in the Breztri excipient market?

The addressable opportunity is broader than supplying one inactive ingredient. It includes a platform strategy for inhaled triple therapy.

Highest-value opportunities

Opportunity	Strategic value	Entry difficulty
Low-GWP pMDI propellant	High	High
Pharmaceutical-grade phospholipid porous particles	High	High
Generic-compatible suspension platform	High	High
Device-compatible valve and actuator materials	Medium-high	Medium-high
Inhalation analytical testing	Medium	Medium
Contract particle engineering	High	Medium-high
Conventional HFA-134a supply	Medium	Medium
Packaging and extractables testing	Medium	Medium

A supplier targeting AstraZeneca should position around validated performance rather than price. The strongest commercial package would combine excipient supply, particle engineering, inhalation analytics, regulatory documentation and scale-up support.

Key Takeaways

• Breztri Aerosphere is a three-drug COPD maintenance therapy delivered through AstraZeneca’s Aerosphere pMDI platform.
• HFA-134a is the labeled propellant; phospholipid-based porous particles are central to the platform’s suspension strategy.
• The most defensible excipient opportunities are low-GWP propellants, porous phospholipid particles and device-compatible inhalation materials.
• Generic entry is constrained by formulation, device, method-of-use and manufacturing patents.
• Breztri is a small-molecule inhaled product; biosimilar competition does not apply.
• The principal commercial risk is propellant transition, while the principal technical barrier is reproducing suspension and aerosol performance.
• Suppliers with inhalation-grade quality systems and full extractables, leachables and aerodynamic-performance packages have the strongest positioning.

FAQs About Breztri Aerosphere Excipients and Commercial Strategy

Does Breztri contain lactose?

No. Breztri is a pMDI suspension product and does not use lactose as the principal carrier excipient. Lactose is more commonly associated with dry-powder inhalers.

Is HFA-134a in Breztri being replaced?

No publicly established replacement has been identified in the current U.S. product label. HFA-152a and HFO-1234ze are the leading lower-global-warming-potential candidates for future pMDI reformulation programs.

Can a generic Breztri use a different excipient?

Potentially, but it must demonstrate pharmaceutical equivalence or otherwise satisfy the applicable FDA pathway. A different excipient can affect device performance, aerosol characteristics, stability and patent exposure.

Is Breztri protected by biologic exclusivity?

No. Breztri contains three small-molecule active ingredients and is not subject to the biosimilar framework used for biologic products.

What is the most valuable Breztri-related excipient capability?

Commercially, the strongest capability is a qualified co-suspension particle platform that can support low-variability aerosol delivery, scale-up, device compatibility and regulatory documentation.

References

1. U.S. Food and Drug Administration. (2024). Breztri Aerosphere: Prescribing information, NDA 212122.
2. AstraZeneca. (2024). Aerosphere inhalation technology and product information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Food and Drug Administration. (2023). Metered dose inhaler and dry powder inhaler drug products: Guidance for industry.
5. European Parliament and Council of the European Union. (2024). Regulation (EU) 2024/573 on fluorinated greenhouse gases.