List of Excipients in Branded Drug PYRAZINAMIDE

Generic Drugs Containing PYRAZINAMIDE

Company	Ingredient	NDC	Excipient
Hikma Pharmaceuticals USA Inc	pyrazinamide	0054-0812	CELLULOSE, MICROCRYSTALLINE
Hikma Pharmaceuticals USA Inc	pyrazinamide	0054-0812	CROSCARMELLOSE SODIUM
Hikma Pharmaceuticals USA Inc	pyrazinamide	0054-0812	DIBASIC CALCIUM PHOSPHATE DIHYDRATE
Hikma Pharmaceuticals USA Inc	pyrazinamide	0054-0812	SILICON DIOXIDE
Hikma Pharmaceuticals USA Inc	pyrazinamide	0054-0812	STEARIC ACID
Major Pharmaceuticals	pyrazinamide	0904-6696	MAGNESIUM STEARATE

What are the Most Frequently-Used Excipients in PYRAZINAMIDE?

# Of NDCs	Excipient
1	CALCIUM PHOSPHATE, DIBASIC, DIHYDRATE
5	CELLULOSE, MICROCRYSTALLINE
5	CROSCARMELLOSE SODIUM
4	DIBASIC CALCIUM PHOSPHATE DIHYDRATE
11	MAGNESIUM STEARATE
1	POVIDONE

Pyrazinamide Excipient Strategy and Commercial Opportunities

Last updated: September 6, 2026

Pyrazinamide is an established tuberculosis drug with limited patent protection, multiple generic suppliers, and high public-sector demand. The strongest commercial opportunities are not new chemical entity exclusivity. They are pediatric dispersible tablets, fixed-dose combinations, taste-masked oral liquids, heat- and humidity-stable products, and procurement-qualified formulations.

Pyrazinamide is used with rifampicin, isoniazid, and ethambutol during the intensive phase of treatment for drug-susceptible tuberculosis. Its principal formulation advantages are high aqueous solubility and compatibility with immediate-release oral products. Its main development challenges are bitter taste, dose size, regimen adherence, excipient compatibility in fixed-dose combinations, and low-margin global procurement markets.

What is the regulatory status of pyrazinamide?

Pyrazinamide is an FDA-approved antitubercular drug used only as part of a multidrug tuberculosis regimen. The FDA labeling identifies it for the initial intensive phase of treatment with other antitubercular agents, usually for approximately two months in drug-susceptible disease [1].

Regulatory attribute	Pyrazinamide position
Active ingredient	Pyrazinamide
Therapeutic class	Antimycobacterial
Primary use	Tuberculosis treatment
Typical dosage form	Immediate-release tablet
Common strengths	500 mg and 750 mg; product availability varies
FDA pathway	Generic approvals and legacy products
New chemical entity exclusivity	Expired
Orphan-drug exclusivity	Not a principal commercial protection
Biosimilar pathway	Not applicable
Orange Book relevance	Product-specific listings for approved generic products; no biologic reference-product framework
Main market	Public-sector tuberculosis programs and generic retail channels

The World Health Organization recommends pyrazinamide as part of the standard six-month regimen for drug-susceptible tuberculosis. Pediatric dosing is weight-based and commonly administered at approximately 35 mg/kg daily, within the WHO-recommended dosing range [2].

What excipients are used in pyrazinamide tablets?

Immediate-release tablets generally use conventional excipients because pyrazinamide is sufficiently soluble for rapid dissolution. The commercial objective is low-cost, robust compression rather than modified release.

Representative excipient functions include:

Formulation function	Common excipient options	Commercial purpose
Diluent	Microcrystalline cellulose, lactose, dibasic calcium phosphate, starch	Controls tablet weight and compressibility
Binder	Povidone, pregelatinized starch, hydroxypropyl cellulose	Improves granule and tablet strength
Disintegrant	Croscarmellose sodium, sodium starch glycolate, crospovidone	Supports rapid breakup after administration
Lubricant	Magnesium stearate, sodium stearyl fumarate	Reduces sticking and ejection force
Glidant	Colloidal silicon dioxide, talc	Improves powder flow
Opacifier or colorant	Titanium dioxide, approved iron oxides	Supports product identification
Film coating	Hypromellose, polyethylene glycol, talc	Improves swallowability and handling

The exact excipient system must be selected through compatibility, dissolution, stability, and process studies. Public labels for pyrazinamide products show that manufacturers use conventional tablet excipients, but composition varies by supplier and market [3].

Which excipient properties matter most?

The critical properties are:

1. Fast and reproducible disintegration.
2. Acceptable tablet hardness at low compression force.
3. Stable dissolution across tropical humidity conditions.
4. Low risk of sticking during high-speed compression.
5. Compatibility with rifampicin, isoniazid, and ethambutol in fixed-dose combinations.
6. Acceptable taste and mouthfeel if the product is intended for pediatric dispersion.

Pyrazinamide does not require a complex solubilization platform in a standard tablet. The development budget is better directed toward manufacturability, taste management, and long-term stability.

What formulation patents protect pyrazinamide products?

Pyrazinamide has been used clinically for decades. Core composition-of-matter protection and early product patents have expired. Current competitive protection is more likely to arise from formulation know-how, manufacturing controls, trademark rights, procurement qualification, and regulatory files than from enforceable pyrazinamide molecule patents.

Potentially relevant intellectual-property categories include:

• Fixed-dose combination ratios.
• Pediatric dispersible tablet compositions.
• Taste-masking systems.
• Multiparticulate or granule formulations.
• Low-dust manufacturing processes.
• Moisture-protective packaging.
• Coated particles or granules for oral suspension.
• Combination products designed for rapid dissolution.
• Device or dosing systems for pediatric administration.

A formulation patent must provide a meaningful technical distinction, such as a defined dissolution profile, improved stability, reduced degradation, better taste scores, or a reproducible manufacturing advantage. A simple substitution of one conventional filler for another is unlikely to create strong protection unless the claimed combination produces an unexpected result.

When does pyrazinamide lose exclusivity?

Pyrazinamide has already lost the exclusivity associated with its original approval. The practical market has been generic for many years.

Exclusivity category	Status
New chemical entity exclusivity	Expired
Patent term for the active molecule	Expired
Pediatric exclusivity	No meaningful current barrier
Regulatory exclusivity for ordinary tablets	Not a current market barrier
Reference-product protection	Limited commercial significance
Generic substitution	Established
Biosimilar exclusivity	Not applicable

No commercially material patent cliff remains for ordinary pyrazinamide tablets. The relevant launch question is whether a new product can obtain approval, satisfy quality requirements, and compete in tenders or distribution channels.

How many patents cover pyrazinamide?

The number of historical patent documents involving pyrazinamide is larger than the number of live, commercially relevant rights. Older patents may cover synthesis, combinations, or dosage forms, but the active ingredient itself is not protected by an enforceable modern composition-of-matter patent.

For a new pyrazinamide product, the key freedom-to-operate review should focus on:

• Active patents in the target jurisdictions.
• Patent families covering pediatric dispersible formulations.
• Combination-product claims.
• Manufacturing-process claims.
• Coating and taste-masking claims.
• Regulatory exclusivity attached to a specific reference product.
• Third-party trademarks and trade dress.

The absence of a strong core patent estate does not eliminate risk. It shifts the risk from molecule ownership to formulation claims, process claims, regulatory compliance, and commercial execution.

What pediatric formulations are protected by pyrazinamide excipient strategy?

Pediatric formulations offer the clearest product-development opportunity. Young children may have difficulty swallowing tablets, and standard tablets can produce dosing errors when caregivers split or crush them.

Dispersible tablets

A dispersible tablet can be designed to dissolve in a small volume of water before administration. Key development targets include:

• Rapid dispersion without large particles.
• Low sedimentation.
• Acceptable bitter taste.
• Low tablet friability.
• Adequate stability after opening the container.
• Dose flexibility for weight-band dosing.
• Compatibility with co-formulated antitubercular drugs.

Common excipient tools include mannitol or lactose for mouthfeel, crospovidone or croscarmellose sodium for rapid dispersion, and sweeteners or flavors for taste reduction. Highly porous direct-compression excipients can reduce disintegration time but may increase tablet friability or packaging sensitivity.

Oral granules and powders

Granules may provide better dose flexibility than a fixed-strength tablet. They can be packaged in unit-dose sachets or multidose bottles. The main risks are segregation, dust generation, moisture uptake, and dose nonuniformity.

Oral suspensions

A pyrazinamide suspension can address swallowing barriers but creates more demanding stability and preservative requirements. A commercial suspension must control:

• Sedimentation and redispersibility.
• Sediment caking.
• Viscosity.
• Preservative effectiveness.
• Microbial quality.
• Dose uniformity after shaking.
• In-use stability after opening.

Suspension excipients may include xanthan gum, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, sorbitol, glycerin, sucrose, buffers, preservatives, and flavors. The bitter taste of pyrazinamide makes a suspension more difficult to commercialize than a neutral immediate-release tablet.

What fixed-dose combinations use pyrazinamide?

Pyrazinamide is commercially important as a component of fixed-dose combinations, especially with rifampicin, isoniazid, and ethambutol. Combination products reduce pill burden and support standardized treatment regimens.

A four-drug intensive-phase combination usually contains:

• Rifampicin
• Isoniazid
• Pyrazinamide
• Ethambutol

A three-drug combination may contain rifampicin, isoniazid, and pyrazinamide.

What are the excipient challenges in fixed-dose combinations?

Fixed-dose combinations create technical problems that do not arise in a single-ingredient tablet:

• Different active ingredients have different particle sizes and densities.
• Rifampicin can be sensitive to moisture and chemical interactions.
• Isoniazid may participate in degradation pathways involving other components.
• Ethambutol can affect tablet weight and compression behavior.
• The high pyrazinamide dose can dominate tablet size.
• A single disintegration system must support all active ingredients.
• Dissolution specifications must be met for each component.

A bilayer or multilayer tablet can separate incompatible ingredients, but it increases manufacturing complexity and cost. A monolithic tablet is cheaper but demands stronger formulation and process controls.

For many public-sector markets, the preferred platform is a conventional immediate-release fixed-dose tablet with high dose uniformity, rapid dissolution, and protective packaging.

What generic entry risks exist for pyrazinamide?

Generic entry risk is high because:

• The active ingredient is old and widely manufactured.
• Core patents have expired.
• Multiple suppliers operate in regulated and semi-regulated markets.
• Standard tablet technology is accessible.
• Treatment guidelines support continued use.
• Buyers often prioritize price, registration status, and procurement history.

Generic competition is less intense in products that require:

• WHO prequalification.
• Pediatric dispersible dosage forms.
• Stringent bioequivalence evidence.
• Multi-active fixed-dose combination development.
• Climate-zone IV stability.
• Government tender qualification.
• Reliable supply of pharmaceutical-grade API.

The principal barrier is execution, not patent infringement.

Which companies are challenging pyrazinamide patents?

No major current Paragraph IV campaign is associated with ordinary pyrazinamide tablets. Pyrazinamide is a mature generic product rather than a branded product facing a contemporary patent challenge.

What is the Paragraph IV status of pyrazinamide?

Paragraph IV litigation is generally relevant when an ANDA applicant alleges that a listed patent is invalid, unenforceable, or not infringed. Because pyrazinamide’s core patents expired long ago and the market is populated by generic products, a current Paragraph IV strategy is not the central commercial issue.

A new entrant should still review the FDA Orange Book for the specific reference product and dosage form before filing. Any risk is more likely to involve a formulation or combination patent than the pyrazinamide molecule itself [4].

What is the Orange Book status of pyrazinamide?

The Orange Book is relevant for identifying approved drug products, reference-listed drugs, therapeutic equivalence information, and any listed patents or exclusivity associated with a specific product [4].

For pyrazinamide, the commercial picture is generally:

• Multiple approved generic products.
• Established immediate-release tablet products.
• No active NCE exclusivity.
• No biosimilar reference-product pathway.
• Limited relevance of listed patent barriers for conventional tablets.
• Product-specific review required for each strength and dosage form.

An applicant should avoid assuming that a patent-free tablet market automatically covers a new suspension, dispersible tablet, or fixed-dose combination. Those products may raise separate regulatory and patent questions.

What patent litigation affects pyrazinamide?

Pyrazinamide has no widely recognized current litigation pattern comparable to high-value branded drugs such as GLP-1 agonists, oncology products, or specialty biologics. Litigation exposure is more likely to arise from:

• Contract manufacturing disputes.
• API quality claims.
• Product liability.
• Procurement exclusion.
• Trademark disputes.
• Trade-secret disputes.
• Patent disputes involving a novel formulation or combination.

For a conventional generic tablet, litigation risk is low relative to regulatory and supply-chain risk.

What commercial opportunities exist for pyrazinamide?

1. Pediatric dispersible fixed-dose combinations

This is the strongest product opportunity. A well-designed pediatric combination can compete on dose accuracy, acceptability, packaging, and programmatic usability rather than on molecule exclusivity.

2. WHO-prequalified products

WHO prequalification can improve access to international procurement channels. The process requires evidence of quality, manufacturing compliance, stability, and product performance [5].

3. Climate-stable tablets

Products designed for high heat and humidity can reduce degradation and packaging failures in high-burden regions. Aluminum-aluminum blisters, high-barrier bottles, desiccants, and moisture-controlled manufacturing can support this positioning.

4. Flexible-dose granules

Weight-band dosing and sachet-based granules may address pediatric and decentralized-care needs. The main commercial challenge is packaging cost and the need to demonstrate dose uniformity.

5. Regional manufacturing and licensing

Licensing opportunities may involve:

• Transfer of a pediatric formulation.
• Local production under a technology-transfer agreement.
• Supply of prequalified tablets to national programs.
• Contract manufacturing of fixed-dose combinations.
• Regional packaging and distribution rights.

Unlike a patented branded drug, the value of a pyrazinamide licensing deal is driven by regulatory files, procurement access, manufacturing reliability, and market authorization.

How large is the revenue exposure for pyrazinamide?

Pyrazinamide revenue is linked to tuberculosis incidence, treatment coverage, public procurement, and regimen duration. WHO estimated that approximately 10.8 million people developed tuberculosis in 2023, with more than 1.2 million deaths [6].

Commercial revenue is difficult to attribute because pyrazinamide is often sold inside low-priced fixed-dose combinations. The highest-volume markets are typically public-sector programs, where prices are compressed and contracts may be awarded through competitive tenders.

Revenue exposure is therefore strongest for suppliers with:

• WHO prequalification.
• Large-scale API access.
• Government registrations.
• Reliable tender performance.
• Fixed-dose combination capability.
• Low-cost high-volume manufacturing.
• Supply continuity during procurement cycles.

Standalone pyrazinamide tablets can provide stable volume but usually have limited pricing power. Pediatric combinations and differentiated presentations may support better margins.

How strong is the pyrazinamide patent estate?

The patent estate for ordinary pyrazinamide tablets is weak from a blocking-rights perspective. Product differentiation can still be strong when supported by regulatory data, manufacturing know-how, procurement qualification, and a defensible formulation patent.

Estate component	Strength
Core molecule patent	Very weak or expired
Standard tablet composition	Weak
Pediatric dispersible formulation	Potentially moderate
Taste-masked suspension	Potentially moderate
Fixed-dose combination	Depends on claims and technical results
Manufacturing process	Potentially moderate
Regulatory file and approval	Commercially important
Trademark and brand	Market-specific
Supply qualification	Often highly valuable in public procurement

What manufacturing and IP barriers affect pyrazinamide?

Manufacturing barriers include API impurity control, particle-size consistency, blend uniformity, tablet weight, dissolution, and packaging performance. In fixed-dose combinations, the highest technical risk is maintaining chemical and physical stability for all active ingredients through shelf life.

Potential IP barriers are narrower:

• Active formulation patents.
• Coating and taste-masking claims.
• Combination-product claims.
• Process patents.
• Proprietary excipient systems.
• Device and dosing claims.

A robust development program should use excipient screening, forced-degradation testing, design-of-experiments studies, dissolution profiling, and accelerated stability under high-temperature and high-humidity conditions.

Key Takeaways

• Pyrazinamide is a mature, generic antitubercular drug with no meaningful remaining core-molecule exclusivity.
• Conventional immediate-release tablets require standard excipients rather than advanced delivery technology.
• Pediatric dispersible tablets, granules, suspensions, and fixed-dose combinations offer the best commercial opportunities.
• Taste masking, dispersion, dose flexibility, and tropical stability are the principal formulation priorities.
• The strongest market protections are regulatory approval, WHO prequalification, procurement access, manufacturing reliability, and formulation know-how.
• Paragraph IV litigation and biosimilar risk are not central issues for ordinary pyrazinamide products.
• Revenue is volume-driven and concentrated in public-sector tuberculosis programs.
• A new formulation patent is most credible when it demonstrates improved stability, dissolution, palatability, dose uniformity, or manufacturing performance.

FAQs About Pyrazinamide Excipient Strategy

Can pyrazinamide be formulated as an oral suspension?

Yes. The main development issues are bitter taste, sedimentation, redispersibility, preservative effectiveness, microbial control, and dose uniformity after shaking.

Is pyrazinamide suitable for direct compression?

It may be suitable depending on particle morphology, flow, compressibility, and dose loading. High-dose tablets often require a formulation assessment to control weight variation, hardness, friability, and dissolution.

Which excipients improve the taste of pyrazinamide?

Sweeteners, flavors, polyols, polymeric coatings, ion-exchange systems, and coated granules may reduce perceived bitterness. The appropriate approach depends on dose, dosage form, and stability requirements.

Does pyrazinamide require a modified-release formulation?

Usually no. Standard tuberculosis regimens use immediate-release administration. Modified release would require a clear clinical or adherence benefit to justify added development and regulatory complexity.

Can pyrazinamide be co-formulated with rifampicin?

Yes. It is commonly included in fixed-dose tuberculosis combinations with rifampicin, isoniazid, and sometimes ethambutol. The formulation must address active-ingredient compatibility, dissolution, moisture sensitivity, and dose uniformity.

References

1. U.S. Food and Drug Administration. (n.d.). Pyrazinamide tablets: Prescribing information. FDA/DailyMed.

2. World Health Organization. (2022). WHO consolidated guidelines on tuberculosis: Module 4: Treatment - drug-susceptible tuberculosis treatment. World Health Organization.

3. National Library of Medicine. (n.d.). DailyMed: Pyrazinamide tablet product labeling. U.S. National Library of Medicine.

4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. FDA.

5. World Health Organization. (n.d.). WHO prequalification of medicines. World Health Organization.

6. World Health Organization. (2024). Global tuberculosis report 2024. World Health Organization.