List of Excipients in Branded Drug QUINAPRIL AND HYDROCHLOROTHIAZIDE

Generic Drugs Containing QUINAPRIL AND HYDROCHLOROTHIAZIDE

Company	Ingredient	NDC	Excipient
Chartwell RX LLC	quinapril and hydrochlorothiazide	62135-667	CROSPOVIDONE
Chartwell RX LLC	quinapril and hydrochlorothiazide	62135-667	FD&C YELLOW NO. 6
Chartwell RX LLC	quinapril and hydrochlorothiazide	62135-667	LECITHIN, SOYBEAN
Chartwell RX LLC	quinapril and hydrochlorothiazide	62135-667	MAGNESIUM HYDROXIDE
Chartwell RX LLC	quinapril and hydrochlorothiazide	62135-667	MAGNESIUM STEARATE

What are the Most Frequently-Used Excipients in QUINAPRIL AND HYDROCHLOROTHIAZIDE?

# Of NDCs	Excipient
1	CROSPOVIDONE
1	FD&C YELLOW NO. 6
1	LECITHIN, SOYBEAN
1	MAGNESIUM HYDROXIDE
1	MAGNESIUM STEARATE

Quinapril and Hydrochlorothiazide Excipient Strategy, Patent Status, and Commercial Opportunities

Last updated: September 24, 2026

Quinapril and hydrochlorothiazide is an off-patent, fixed-dose antihypertensive combination with limited branded commercial value but potential niche opportunities in generic reformulation, nitrosamine control, supply reliability, and differentiated oral solid-dose manufacturing. The original product, Accuretic, combined the ACE inhibitor quinapril hydrochloride with the thiazide diuretic hydrochlorothiazide in 10/12.5 mg, 20/12.5 mg, and 20/25 mg strengths. Its core composition and active-ingredient patents are no longer commercially blocking in the United States. The primary opportunity is therefore operational and regulatory rather than exclusivity-driven.

What is quinapril and hydrochlorothiazide used for?

Quinapril and hydrochlorothiazide is used for the treatment of hypertension in patients requiring combination therapy. Quinapril inhibits angiotensin-converting enzyme, reducing angiotensin II formation. Hydrochlorothiazide promotes renal sodium and water excretion.

The combination offers two complementary mechanisms:

Component	Pharmacologic class	Primary role
Quinapril	ACE inhibitor	Reduces vasoconstriction and aldosterone activity
Hydrochlorothiazide	Thiazide diuretic	Increases sodium and fluid excretion
Combination	Fixed-dose antihypertensive	Improves regimen consolidation and may reduce pill burden

The product is not generally positioned as a first-line combination against newer fixed-dose ACE inhibitor, ARB, calcium-channel blocker, and thiazide products. Its commercial relevance is concentrated in patients already controlled on quinapril-based therapy, institutional formularies, and markets where low-cost ACE inhibitor combinations remain established.

What formulations are protected by the quinapril and hydrochlorothiazide product?

The historical Accuretic formulation was an immediate-release, film-coated tablet. The principal strengths were:

Strength	Quinapril hydrochloride	Hydrochlorothiazide
Low dose	10 mg	12.5 mg
Intermediate dose	20 mg	12.5 mg
High dose	20 mg	25 mg

The formulation uses conventional oral solid-dose excipients. The inactive-ingredient system has historically included materials such as magnesium carbonate, gelatin, crospovidone, magnesium stearate, talc, and colorants, although exact excipient composition depends on the manufacturer and strength.[1]

The formulation challenge is not complex drug delivery. It is chemical stability, content uniformity, dissolution, tablet robustness, and control of nitrosamine-related impurities. Quinapril is particularly relevant to nitrosamine risk management because quinapril molecules and manufacturing conditions can create pathways for N-nitroso-quinapril formation.

What excipient functions matter most?

Excipient function	Commercial objective	Key development issue
Filler or compression aid	Achieve tablet weight and hardness	Avoid excessive tablet size
Disintegrant	Support rapid immediate-release dissolution	Balance against friability
Lubricant	Improve ejection from tooling	Control over-lubrication and dissolution impact
Alkalinizing or buffering component	Improve quinapril stability	Confirm compatibility with HCTZ and packaging
Glidant	Improve powder flow	Maintain blend uniformity at low drug load
Film coat	Protect tablet and provide identification	Minimize moisture transfer and color variability
Colorant	Strength differentiation	Support product identification and error reduction

A development program should prioritize excipients with established compendial status and low extractables and leachables risk. A direct, Q1/Q2-aligned formulation can reduce regulatory complexity for an ANDA, but a formulation that changes the microenvironmental pH may offer better impurity control. That tradeoff must be evaluated against bioequivalence, dissolution, stability, and scale-up requirements.

What is the Orange Book status of quinapril and hydrochlorothiazide?

The combination has no meaningful remaining United States patent barrier for ordinary generic entry. The original branded product was approved decades ago, and any compound or combination patents associated with quinapril, hydrochlorothiazide, or their early fixed-dose products have expired.

The Orange Book is the controlling source for current listed patents, exclusivity, and reference-product status. Historical and current FDA records identify Accuretic as a quinapril hydrochloride and hydrochlorothiazide product, but the product is no longer a commercially significant protected brand.[2]

Regulatory item	Status
Reference product	Accuretic
Active ingredient	Quinapril hydrochloride plus hydrochlorothiazide
Dosage form	Immediate-release tablet
US exclusivity	Expired
Core composition patents	Expired
Current blocking patent risk	Low
Generic pathway	Primarily ANDA, subject to reference-product and market-availability requirements
Paragraph IV exposure	Low practical relevance unless a new patent is listed against a specific formulation or use

When does quinapril and hydrochlorothiazide lose exclusivity?

The product lost meaningful exclusivity years ago. Quinapril and hydrochlorothiazide are both long-established small molecules. The relevant opportunities now arise from generic approval, manufacturing economics, impurity control, supply continuity, and regional registrations rather than patent-protected pricing.

No current patent estate appears capable of supporting premium pricing for an ordinary immediate-release quinapril/hydrochlorothiazide tablet. A newly developed formulation could create patentable subject matter only if it contains a genuinely novel and non-obvious stability, impurity-control, delivery, or manufacturing feature.

How many patents cover quinapril and hydrochlorothiazide?

For the conventional immediate-release combination, the commercially relevant number of unexpired blocking patents is effectively zero in the United States.

Historical patent protection included:

1. Quinapril compound and related ACE-inhibitor chemistry.
2. Quinapril pharmaceutical compositions.
3. Fixed-dose quinapril and hydrochlorothiazide combinations.
4. Manufacturing and process claims associated with the active ingredients.

Those rights have reached the end of their statutory terms. Any current patent analysis must separate expired historical patents from newly issued patents covering a specific formulation, impurity-control method, polymorph, process, or jurisdiction.

What patent claims could support a new quinapril combination product?

Potentially protectable subject matter could include:

• A low-nitrosamine manufacturing process.
• A formulation that limits formation of N-nitroso-quinapril during storage.
• A specific alkaline microenvironment that improves quinapril stability.
• A moisture-controlled tablet or blister configuration.
• A novel modified-release system.
• A process that produces a defined solid form or impurity profile.
• A combination with a new active pharmaceutical ingredient or therapeutic use.

A patent directed only to the use of ordinary excipients in a conventional immediate-release tablet would face substantial obviousness and enablement risk. Commercial value would depend on whether the claim creates a meaningful regulatory or manufacturing advantage.

What was the impact of nitrosamine contamination on quinapril products?

Nitrosamine contamination materially changed the commercial assessment of quinapril products. In 2022, recalls and market withdrawals affected quinapril and quinapril/hydrochlorothiazide products because N-nitroso-quinapril levels exceeded applicable acceptable-intake limits or raised concerns under FDA nitrosamine guidance.[3]

The risk is commercially important because it can affect:

• Active pharmaceutical ingredient selection.
• Supplier qualification.
• Process solvents and reagents.
• Packaging configuration.
• Long-term and accelerated stability.
• Batch release testing.
• Shelf-life assignment.
• Regulatory inspection readiness.

FDA guidance treats nitrosamine control as a lifecycle obligation rather than a one-time release test. Manufacturers must evaluate nitrosating agents, amines, catalysts, solvents, recovered materials, water systems, storage conditions, and cross-contamination pathways.[4]

How should excipients be selected to reduce nitrosamine risk?

An excipient strategy should use a risk-based control plan:

1. Qualify excipient suppliers for nitrite and nitrate variability.
2. Test high-risk excipients, especially those derived from natural or variable-source materials.
3. Avoid unnecessary nitrosating conditions during granulation or coating.
4. Evaluate magnesium-containing, gelatin-based, and other functional excipients for lot-to-lot variability.
5. Control water activity and moisture ingress.
6. Use packaging that limits humidity exposure.
7. Test finished product throughout stability, not only at release.
8. Establish a process-specific N-nitroso-quinapril specification.

A direct-compression process may reduce exposure to water and heat compared with wet granulation. It may also improve process simplicity, but only if blend uniformity, tablet hardness, and dissolution are acceptable. Dry granulation is another option where flow or compressibility requires improvement.

What commercial opportunities exist for quinapril and hydrochlorothiazide?

The largest opportunities are niche and execution-based.

1. Reliable generic supply

Supply continuity is valuable after recalls and manufacturer withdrawals. A company that can establish a clean, validated supply chain may obtain institutional contracts even without patent protection.

2. Low-nitrosamine product positioning

A manufacturer can differentiate through documented control of N-nitroso-quinapril, shortens impurity investigation timelines, and stable long-term performance. This positioning is more likely to support procurement preference than a consumer premium.

3. Private-label and regional licensing

The product may fit regional licensing models involving:

• Contract manufacturing.
• Local marketing authorization holders.
• Hospital and government tenders.
• Private-label generic portfolios.
• Emerging-market hypertension programs.

4. Portfolio bundling

Quinapril/hydrochlorothiazide can be bundled with other cardiovascular generics, such as quinapril alone, hydrochlorothiazide alone, lisinopril/hydrochlorothiazide, enalapril/hydrochlorothiazide, or ARB/thiazide products. The commercial rationale is portfolio breadth rather than standalone growth.

5. Packaging and adherence products

Calendar blister packs, unit-dose packaging, and pharmacy automation formats may improve institutional usability. Packaging claims generally do not create strong exclusivity, but they can support procurement differentiation.

How does quinapril and hydrochlorothiazide compare with competing combinations?

Product class	Market position	Patent risk	Commercial outlook
Quinapril/HCTZ	Mature ACE inhibitor/thiazide combination	Very low	Niche generic
Lisinopril/HCTZ	Broad generic use and strong prescriber familiarity	Very low	Larger generic market
Enalapril/HCTZ	Established ACE inhibitor combination	Very low	Stable, mature demand
Losartan/HCTZ	Widely used ARB/thiazide combination	Very low	Stronger competitive position
Valsartan/HCTZ	Established ARB/thiazide combination	Very low	Broad generic and branded history
Amlodipine/benazepril	ACE inhibitor/calcium-channel blocker	Low to moderate by product	More differentiated clinical positioning

Quinapril/hydrochlorothiazide faces competitive pressure from lisinopril/hydrochlorothiazide and ARB/thiazide combinations. ARBs may be preferred for patients who develop ACE-inhibitor cough. Lisinopril has stronger generic recognition and more extensive prescribing history.

Which companies are challenging quinapril and hydrochlorothiazide?

The competitive field consists primarily of generic manufacturers and contract suppliers rather than patent challengers. Generic competition has historically included companies with ANDA portfolios in cardiovascular products, although individual product availability changes following recalls, discontinuations, and manufacturing decisions.

There is no meaningful current Paragraph IV campaign associated with the original Accuretic product. Paragraph IV litigation would become relevant only if a new patent were listed for a reformulated product or a new method of use.

What FDA regulatory pathway applies?

A conventional generic tablet would generally proceed through an ANDA referencing the FDA-designated reference product. The applicant must demonstrate pharmaceutical equivalence and bioequivalence and satisfy current FDA requirements for manufacturing, stability, impurity control, labeling, and quality systems.[2]

A 505(b)(2) application could be considered for a materially differentiated product, such as:

• Modified release.
• A novel dosage form.
• A new combination strength.
• A clinically meaningful formulation change.
• A new route of administration.

For a conventional immediate-release tablet, an ANDA is usually the more efficient pathway. A 505(b)(2) strategy would impose additional clinical and regulatory costs without creating value unless the product has a meaningful differentiation.

What generic launch risks exist?

The major launch risks are operational:

Risk	Impact
N-nitroso-quinapril formation	Recall, import alert, or regulatory delay
Weak demand forecasts	Excess inventory and low manufacturing utilization
Limited API suppliers	Cost volatility and supply interruption
Reference-product discontinuation	Complicated regulatory and sourcing strategy
Bioequivalence failure	Delayed approval and reformulation
Low reimbursement value	Weak pricing power
Competitive ACE inhibitor alternatives	Slow formulary adoption
Stability failures	Reduced shelf life and higher testing burden

The product is most commercially attractive where the applicant already has cardiovascular manufacturing capacity, a qualified API source, and an established generic sales channel. It is less attractive as a standalone launch requiring new infrastructure.

What geographic markets offer the best opportunity?

The United States offers regulatory clarity but limited volume and low pricing. European markets may offer opportunities through national generic registrations, although demand is fragmented and ACE inhibitor combinations compete with more widely used alternatives. Emerging markets may provide larger volume potential, but local registration, tender pricing, pharmacopoeial requirements, and supply-chain reliability determine commercial performance.

A regional strategy should prioritize markets where:

• Quinapril remains included in treatment guidelines or formularies.
• The combination has an established prescribing base.
• Competitors have experienced supply disruptions.
• Local manufacturing or packaging provides tender advantages.
• Nitrosamine-control documentation is accepted by the regulator.

How strong is the patent estate for quinapril and hydrochlorothiazide?

The patent estate is weak for the conventional product and cannot support meaningful exclusionary pricing. The commercial moat is more likely to come from:

• Validated low-impurity manufacturing.
• Reliable API sourcing.
• Regulatory approvals across multiple jurisdictions.
• Established hospital contracts.
• Efficient tablet production.
• Stable shelf life.
• A differentiated packaging or adherence platform.

A new patent strategy should focus on measurable technical effects. The strongest candidates are likely to involve impurity suppression, process controls, or stability performance rather than ordinary excipient substitution.

Key Takeaways

• Quinapril/hydrochlorothiazide is a mature, off-patent immediate-release combination.
• Accuretic’s historical strengths were 10/12.5 mg, 20/12.5 mg, and 20/25 mg.
• Current commercial value is driven by generic supply, not exclusivity.
• N-nitroso-quinapril control is the central formulation and manufacturing issue.
• Direct compression or dry granulation may reduce process-related impurity risk, subject to dissolution and uniformity validation.
• An ANDA is the likely pathway for a conventional generic tablet.
• A 505(b)(2) strategy would require meaningful formulation or clinical differentiation.
• The strongest commercial candidates already have cardiovascular distribution and quality infrastructure.
• Potential new patent value lies in impurity control, stability, packaging, or genuinely differentiated delivery systems.
• Competitive pressure from lisinopril/hydrochlorothiazide and ARB/thiazide products limits standalone market potential.

FAQs

Is quinapril hydrochlorothiazide still available in the United States?

Availability has been affected by product discontinuations and recalls, including actions associated with N-nitroso-quinapril concerns. FDA product-status records and current distributor listings determine commercial availability at a given time.[2,3]

Can a generic manufacturer use the original Accuretic excipients?

A generic manufacturer can use the same or different excipients if the formulation meets applicable pharmaceutical equivalence, bioequivalence, quality, stability, labeling, and manufacturing requirements. Exact excipient matching is not always required, but formulation differences must not create clinically relevant performance differences.

Does hydrochlorothiazide create nitrosamine risk by itself?

Hydrochlorothiazide is not the principal molecule associated with the N-nitroso-quinapril issue. The risk assessment must cover the complete formulation and manufacturing process because excipients, solvents, water, packaging, and storage conditions can influence impurity formation.

Could a low-nitrosamine formulation receive new patent protection?

Potentially, but a patent would require novel and non-obvious technical features supported by data. A formulation that merely substitutes a routine excipient without a demonstrated technical effect is unlikely to provide strong protection.

Is quinapril hydrochlorothiazide commercially attractive for a new entrant?

It is attractive mainly for an established generic or contract manufacturer with low incremental costs, qualified API suppliers, and cardiovascular distribution. It is a weak standalone investment where the business case depends on premium pricing or broad branded demand.

References

1. DailyMed. (n.d.). Accuretic: Quinapril hydrochloride and hydrochlorothiazide tablet, film coated. U.S. National Library of Medicine.

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

3. U.S. Food and Drug Administration. (2022). FDA updates and recalls involving quinapril and quinapril/hydrochlorothiazide products. FDA.

4. U.S. Food and Drug Administration. (2023). Control of nitrosamine impurities in human drugs: Guidance for industry. FDA.