List of Excipients in Branded Drug PIRFENIDONE CAPSULE, 267 MG

Generic Drugs Containing PIRFENIDONE CAPSULE, 267 MG

Company	Ingredient	NDC	Excipient
Macleods Pharmaceuticals Limited	pirfenidone capsule, 267 mg	33342-461	AMMONIA
Macleods Pharmaceuticals Limited	pirfenidone capsule, 267 mg	33342-461	BROWN IRON OXIDE
Macleods Pharmaceuticals Limited	pirfenidone capsule, 267 mg	33342-461	CROSCARMELLOSE SODIUM
Macleods Pharmaceuticals Limited	pirfenidone capsule, 267 mg	33342-461	FERROSOFERRIC OXIDE
Macleods Pharmaceuticals Limited	pirfenidone capsule, 267 mg	33342-461	GELATIN

What are the Most Frequently-Used Excipients in PIRFENIDONE CAPSULE, 267 MG?

# Of NDCs	Excipient
1	AMMONIA
1	BROWN IRON OXIDE
1	CROSCARMELLOSE SODIUM
1	FERROSOFERRIC OXIDE
1	GELATIN

Pirfenidone 267 mg Capsule Excipient Strategy and Commercial Opportunities

Last updated: August 2, 2026

Pirfenidone 267 mg capsules are an established immediate-release product with a relatively simple excipient platform. The commercial opportunity is unlikely to come from basic substitution of excipients. It is more likely to come from lower-cost manufacturing, improved powder handling, tighter content uniformity, better capsule robustness, differentiated titration packs, and alternative delivery systems that reduce the burden of three-times-daily dosing. The U.S. market is primarily an ANDA-driven generic market, while formulation innovation may support 505(b)(2), regional generic, or licensing strategies.

What excipients are used in pirfenidone 267 mg capsules?

The reference product, Esbriet, uses conventional solid oral excipients suitable for an immediate-release hard gelatin capsule. The FDA-approved labeling identifies the following core inactive ingredients:

Excipient	Primary function in the capsule
Microcrystalline cellulose	Diluent, compressibility and bulk
Croscarmellose sodium	Disintegrant
Povidone	Binder and granulation aid
Colloidal silicon dioxide	Glidant and anti-caking agent
Magnesium stearate	Lubricant
Gelatin	Capsule shell
Titanium dioxide and iron oxide pigments	Capsule-shell opacity and color

The exact grade, particle-size distribution, moisture content, supplier, and processing conditions can affect dissolution, fill-weight variability, capsule-machine performance, and stability. FDA labeling identifies ingredient classes but does not necessarily disclose the complete manufacturing design space or supplier specifications. [1]

Pirfenidone capsules are immediate-release products. The excipient system therefore needs to support rapid drug release rather than sustained release, gastroretention, or enteric protection.

What is the optimal formulation strategy for pirfenidone 267 mg capsules?

The lowest-risk formulation strategy is a direct-compression or dry-granulation blend based on microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, and magnesium stearate. Povidone can be retained where granulation or stronger agglomerate formation is needed.

Recommended formulation objectives

Formulation objective	Commercial relevance	Preferred excipient approach
Rapid immediate release	Supports bioequivalence and avoids release-related regulatory risk	Croscarmellose sodium with low-to-moderate lubricant loading
Uniform capsule fill	Reduces weight variation and rejects	Spray-dried or co-processed MCC, controlled particle-size silica
Low segregation	Important because the dose is relatively small compared with capsule fill mass	Narrow particle-size distribution and matched bulk density
Stable moisture profile	Protects flow and dissolution over shelf life	Low-moisture excipient grades and controlled packaging
Efficient high-speed encapsulation	Reduces unit cost	Direct-compression excipients or robust dry granulation
Capsule-shell integrity	Reduces cracking, brittleness, and leakage	Controlled gelatin moisture and validated storage conditions
Consistent dissolution	Supports ANDA equivalence	Conservative excipient substitution and discriminatory dissolution testing

A formulation developer should avoid unnecessary complexity. Novel surfactants, lipids, ion-pairing systems, or complex polymer matrices may increase development and regulatory burden without creating a meaningful benefit for an immediate-release capsule.

Which excipients offer the strongest commercial opportunity?

Microcrystalline cellulose

MCC is the largest formulation opportunity because it controls bulk density, flow, compressibility, and capsule-fill performance. A standard grade may be adequate for low-speed filling, but a high-functionality or co-processed grade can improve:

• Powder flow into the dosator or tamping station
• Fill-weight consistency
• Drug distribution
• Resistance to segregation
• Manufacturing throughput

The main opportunity is not replacing MCC entirely. It is selecting a grade that reduces process variability and improves the economics of high-volume encapsulation.

Croscarmellose sodium

Croscarmellose sodium can support rapid capsule opening and drug dispersion. Excessive loading, however, can increase powder volume and complicate blend uniformity. The strongest development strategy is to compare intragranular and extragranular placement where wet or dry granulation is used.

A lower-cost alternative such as sodium starch glycolate may be technically viable, but it should be evaluated against dissolution, robustness to compression or compaction, and the reference product's release profile. A formulation that meets a single dissolution endpoint but shows different behavior across pH and agitation conditions can create bioequivalence risk.

Povidone

Povidone has value when the formulation requires granulation, improved particle binding, or reduced segregation. For a direct-fill capsule, its role may be limited. Excessive binder content can slow disintegration or create harder agglomerates.

The commercial decision is therefore process-dependent:

• Direct blend: minimize or eliminate povidone if blend performance permits.
• Dry granulation: use a controlled amount to improve granule integrity.
• Wet granulation: use only where the process materially improves uniformity or flow.

Colloidal silicon dioxide

Colloidal silicon dioxide is a relatively small cost component but can have a disproportionate effect on manufacturability. It improves flow and reduces cohesion, particularly in formulations containing fine pirfenidone particles.

The risk is over-lubrication or excessive surface coating of drug particles, which may affect wetting and dissolution. Supplier grade, mixing sequence, and shear exposure should be treated as critical process parameters.

Magnesium stearate

Magnesium stearate is necessary for process lubrication but is a common source of dissolution variability. Longer blending times and high shear can create a hydrophobic coating around particles. The preferred strategy is a short, controlled lubrication step with defined endpoint criteria.

A low-metal or alternative lubricant may be useful for specific manufacturing platforms, but it has limited standalone commercial differentiation unless it improves dissolution, stability, or equipment performance.

How can excipients improve pirfenidone capsule tolerability?

Pirfenidone labeling identifies gastrointestinal adverse reactions, including nausea, dyspepsia, vomiting, and diarrhea, as clinically relevant events. The label recommends administration with food to reduce peak-related tolerability problems. [1]

An excipient change alone is unlikely to eliminate pirfenidone's systemic adverse effects. It may, however, influence local dissolution behavior, gastric dispersion, and the rate of drug availability.

Potential approaches include:

1. Controlled particle-size reduction to improve dissolution without creating excessive early exposure.
2. Wetting optimization using conventional, well-characterized excipients.
3. Multiparticulate or granulated fills that reduce localized drug concentration in the stomach.
4. Delayed or extended release for a separate development program.
5. A food-compatible formulation with reduced sensitivity to meal composition.

The last two approaches may require clinical pharmacokinetic work and could fall outside a conventional ANDA strategy. A modified-release product would need to demonstrate that altered exposure does not reduce efficacy or create new safety concerns.

What formulation patents could protect pirfenidone capsule products?

The basic pirfenidone molecule and the original Esbriet product have been marketed for years. Core compound and early use patents are generally less likely to provide a durable barrier than formulation-specific rights.

Potentially protectable subject matter includes:

• A defined particle-size distribution
• A specific polymorph or solid-state form
• A low-impurity composition
• A specified dissolution profile
• A capsule fill with defined excipient ratios
• A moisture-controlled formulation
• A multiparticulate or granulated delivery system
• A modified-release profile
• A titration regimen linked to a particular dosage form
• A manufacturing process that produces a defined critical quality attribute

An excipient patent is commercially stronger when it claims a measurable product property rather than a broad list of conventional ingredients. A claim limited to MCC, croscarmellose sodium, povidone, silica, and magnesium stearate may face prior-art and obviousness challenges unless it includes a non-obvious ratio, process condition, performance result, or stability benefit.

What is the FDA regulatory pathway for pirfenidone 267 mg capsules?

A conventional generic immediate-release capsule would generally be developed through an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act. The applicant must establish pharmaceutical equivalence and bioequivalence to the reference listed drug.

The main regulatory workstreams are:

Workstream	Relevance to pirfenidone capsules
Pharmaceutical equivalence	Same active ingredient, strength, dosage form, and route
Inactive-ingredient review	Excipients must be acceptable for the route and dosage form
Comparative dissolution	Sensitive testing across relevant media and conditions
Bioequivalence	Pharmacokinetic comparison against the reference product
Stability	Demonstrates shelf life under ICH conditions
Container closure	Protects capsules from moisture and physical damage
Labeling	Must conform to the reference labeling, subject to permitted changes
Manufacturing controls	Must control blend uniformity, fill weight, dissolution, and impurities

A materially different formulation, delivery system, or dosing regimen may require a 505(b)(2) application rather than an ANDA. This pathway can support commercial differentiation but typically requires a larger clinical and regulatory package.

When does pirfenidone lose exclusivity, and what is the generic-entry risk?

Pirfenidone is no longer protected solely by the novelty of its active ingredient. The relevant U.S. competitive barriers are now product-specific patents, regulatory exclusivity, approved generic competition, manufacturing capability, and payer access.

The practical risk profile is:

Barrier	Risk assessment
Core active-ingredient patent	Low as a long-term barrier
Conventional excipient formulation	Low unless tied to a valid, enforceable claim
Method-of-use patents	Relevant only if unexpired and listed or enforceable against the proposed label
Orange Book-listed patents	Must be reviewed against the current FDA entry
Regulatory exclusivity	Generally less significant for an established small molecule
Manufacturing complexity	Moderate; high-volume encapsulation and uniformity control matter
Market access	Significant, because generic substitution and payer contracting can compress price
Modified-release product	Higher regulatory risk but greater differentiation potential

Paragraph IV challenges are most relevant where an unexpired Orange Book-listed patent remains. A generic applicant challenging such a patent may trigger Hatch-Waxman litigation and, depending on the patent and timing, a 30-month stay of approval. The Orange Book and FDA patent-listing records should control the current analysis. [2]

What generic launch scenarios exist for pirfenidone 267 mg capsules?

Scenario 1: Standard ANDA launch

This is the lowest-risk path. The applicant matches the reference capsule's strength, release characteristics, and labeling. Commercial success depends on manufacturing cost, launch timing, wholesaler access, and payer contracting.

Scenario 2: Low-cost formulation platform

The applicant uses direct encapsulation with optimized MCC, silica, and lubricant grades. The objective is to reduce granulation, improve throughput, and lower batch failure risk. This approach offers operational savings rather than patent-based differentiation.

Scenario 3: Titration-pack strategy

Pirfenidone therapy is initiated with dose escalation before reaching the maintenance dose. A commercial package containing 267 mg capsules in a structured titration configuration can improve dispensing convenience and reduce medication errors. The opportunity may involve packaging, labeling, adherence support, and pharmacy workflow rather than a new excipient.

Scenario 4: Modified-release or reduced-frequency product

A once-daily or twice-daily product could address the burden associated with three-times-daily administration. This would be a higher-value opportunity but would require proof of comparable efficacy, safety, exposure, and tolerability. It is more suitable for a 505(b)(2) strategy or a licensing program than a routine ANDA.

Scenario 5: Regional licensing

A manufacturer with low-cost API access, capsule production, or regulatory registrations could license a conventional product into markets where pirfenidone remains underpenetrated. Geographic value depends on local patent status, reference-product requirements, pricing controls, and registration timelines.

How strong is the patent estate for an excipient-optimized pirfenidone capsule?

A conventional excipient-only formulation has limited patent strength. The strongest potential estate would combine:

• A narrowly defined composition;
• A reproducible manufacturing process;
• A demonstrated dissolution or stability advantage;
• A clinically relevant exposure or tolerability benefit;
• Claims covering multiple capsule-fill and scale-up embodiments.

A useful patent program could include separate claims for composition, process, capsule product, dissolution profile, and packaging. The claims should avoid unnecessary dependence on a single supplier or narrow excipient grade unless that limitation produces a measurable performance advantage.

Patent value also depends on whether the product can be substituted automatically under local law. A technically differentiated product may still face rapid generic erosion if regulators treat it as therapeutically equivalent and payers do not reward the difference.

Which companies are positioned to challenge or compete with pirfenidone products?

Competition comes from several groups:

• Established generic pharmaceutical companies with ANDA infrastructure;
• Regional manufacturers with pirfenidone registrations;
• Contract development and manufacturing organizations;
• API manufacturers with integrated capsule operations;
• Developers of idiopathic pulmonary fibrosis therapies with alternative mechanisms;
• Companies developing improved oral delivery systems.

The principal commercial competitor to an excipient-optimized capsule is usually another low-cost generic, not a patented excipient platform. Differentiation must therefore be tied to measurable performance, supply reliability, patient convenience, or reimbursement.

What manufacturing and IP barriers affect commercial opportunity?

The key manufacturing barriers are operational rather than chemical:

• Pirfenidone blend uniformity at commercial scale;
• Segregation during transfer and encapsulation;
• Capsule fill-weight control;
• Lubrication-induced dissolution changes;
• Moisture management;
• Capsule-shell brittleness;
• Cleaning validation and cross-contamination control;
• Consistent impurity and degradation-product profiles.

The key IP barriers are:

• Any currently listed Orange Book patents;
• Process patents covering high-purity pirfenidone;
• Solid-state or particle-engineering patents;
• Modified-release formulations;
• Method-of-use patents linked to dosing or patient populations;
• Patent claims covering a titration regimen or combination therapy.

What commercial opportunities are most attractive?

The opportunity ranking is as follows:

Opportunity	Development risk	Differentiation	Commercial attractiveness
Conventional low-cost 267 mg capsule	Low	Low	Moderate
Optimized high-throughput capsule process	Low to moderate	Low to moderate	High for manufacturers
Titration-pack and adherence packaging	Low	Moderate	Moderate
Improved moisture-protective packaging	Low	Moderate	Moderate
Multiparticulate immediate-release capsule	Moderate	Moderate	Moderate
Modified-release pirfenidone	High	High	Potentially high
Reduced-frequency oral product	High	High	Potentially high
Combination product	High	High	Indication-dependent
Novel excipient platform	Moderate to high	Moderate	Uncertain unless clinically validated

Key Takeaways

• Pirfenidone 267 mg capsules use a conventional immediate-release excipient system centered on MCC, croscarmellose sodium, povidone, colloidal silicon dioxide, and magnesium stearate.
• The strongest near-term opportunity is manufacturing optimization, not a novel excipient claim.
• MCC grade, silica grade, lubrication time, and blend segregation are likely to have the greatest effect on commercial performance.
• A standard generic product would generally follow the ANDA pathway.
• Modified-release, multiparticulate, and reduced-frequency products could support 505(b)(2) or licensing strategies but require greater clinical and regulatory investment.
• Conventional excipient substitutions have weak standalone patent value unless tied to defined performance, process, or stability advantages.
• Titration packaging and supply reliability may create more practical commercial value than minor formulation changes.
• Orange Book patents, FDA exclusivity records, and current ANDA status should govern any launch or Paragraph IV decision. [2,3]

FAQs

Can pirfenidone 267 mg capsules use different excipients from Esbriet?

Yes. A generic applicant may use different inactive ingredients if the formulation meets regulatory requirements, performs comparably, and supports bioequivalence. Changes should be assessed for dissolution, stability, tolerability, and capsule performance.

Is a 267 mg pirfenidone capsule suitable for sustained release?

It can be used as a development platform, but a sustained-release product would be a materially different product. It would require formulation development, pharmacokinetic characterization, and a regulatory strategy beyond a routine immediate-release ANDA.

Which excipient is most important for pirfenidone capsule dissolution?

Croscarmellose sodium, particle-size distribution, and magnesium stearate processing are likely to have the greatest direct effect. Silica and MCC also influence wetting, dispersion, and blend behavior.

Can a titration pack for pirfenidone be patented?

Packaging alone is difficult to protect broadly. A stronger patent position may arise from a package linked to a specific dosing regimen, administration instruction, adherence system, or clinically supported treatment method.

Is pirfenidone a biologic subject to biosimilar competition?

No. Pirfenidone is a small-molecule drug. Competition proceeds through generic drug pathways, including ANDA filings in the United States, rather than biosimilar approval under the Public Health Service Act.

References

1. U.S. Food and Drug Administration. (2023). Esbriet (pirfenidone) prescribing information. Genentech USA, Inc.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/

3. U.S. Food and Drug Administration. (2024). ANDA product-specific guidances for industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/anda-product-specific-guidances-industry

4. U.S. Food and Drug Administration. (2015). Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. Guidance for Industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/waiver-vivo-bioavailability-and-bioequivalence-studies-immediate-release-solid-oral-dosage-forms

5. DailyMed. (2024). Pirfenidone capsule prescribing information. National Library of Medicine. https://dailymed.nlm.nih.gov/