List of Excipients in Branded Drug ALTACE

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Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Pfizer Laboratories Div Pfizer Inc	ALTACE	ramipril	61570-110	FERRIC OXIDE YELLOW
Pfizer Laboratories Div Pfizer Inc	ALTACE	ramipril	61570-110	GELATIN
Pfizer Laboratories Div Pfizer Inc	ALTACE	ramipril	61570-110	STARCH, CORN
Pfizer Laboratories Div Pfizer Inc	ALTACE	ramipril	61570-110	TITANIUM DIOXIDE

ALTACE (Ramipril) Excipient Strategy and Commercial Opportunities

Last updated: September 28, 2026

ALTACE is the U.S. brand for ramipril, an oral angiotensin-converting enzyme inhibitor approved for hypertension, heart failure after myocardial infarction, and cardiovascular-risk reduction. Its core composition is commercially mature, and the original patent and regulatory exclusivity barriers have expired. The strongest current opportunities are not conventional generic ramipril capsules alone. They are differentiated oral delivery, lower-cost excipient systems, fixed-dose combinations, adherence products, and region-specific formulations.

What is ALTACE and which excipients define the reference product?

ALTACE contains ramipril, a prodrug converted in vivo to ramiprilat. The product is supplied as hard gelatin capsules in 1.25 mg, 2.5 mg, 5 mg, and 10 mg strengths in the U.S. [1]

The reference formulation uses conventional excipients for a small-molecule immediate-release capsule. Public product information identifies excipient categories including gelatin, starch-based materials, cellulose-derived materials, sodium lauryl sulfate, and colorants such as iron oxides, depending on strength and presentation. The exact composition should be confirmed against the current reference-label and supplier documentation before a formulation is selected.

Functional role of the ALTACE excipient system

Excipient function	Commercial purpose
Capsule shell	Provides dose containment and rapid release
Pregelatinized starch or related starch material	Filler, binder, and disintegration support
Microcrystalline cellulose or related cellulose material	Diluent and powder-flow aid
Sodium lauryl sulfate	Wetting and dispersion support for a low-dose, poorly soluble drug
Iron oxides or other colorants	Strength differentiation and product identification
Gelatin	Conventional capsule-shell material with broad manufacturing availability

Ramipril is a low-dose active pharmaceutical ingredient. The excipient system therefore determines much of the capsule fill weight, powder flow, blend uniformity, dissolution profile, and manufacturing yield. At 1.25 mg, content uniformity is a more important development issue than drug loading.

What patents protect ALTACE and when did ramipril lose exclusivity?

ALTACE no longer has meaningful U.S. composition-of-matter or regulatory exclusivity. Ramipril generic products have been marketed for years, and the U.S. Orange Book does not provide a current commercial barrier comparable to an active patent estate for the brand. [2]

ALTACE patent timeline

Event	Approximate status
Original ramipril development and patenting	1980s
U.S. approval of ALTACE	1991
Original small-molecule patent protection	Expired
U.S. generic ramipril entry	Occurred after patent expiry and regulatory review
New-drug exclusivity	Expired
Current brand patent leverage	Limited to none for standard ramipril capsules

Historical ramipril patents covered the active compound and related pharmaceutical compositions. Those rights have expired. Any commercial protection today would need to come from a new formulation, delivery device, manufacturing process, combination product, or method-of-use claim that satisfies current patentability standards.

Are there active Paragraph IV challenges to ALTACE?

Paragraph IV litigation is no longer the main market issue for conventional ALTACE capsules. The product has already experienced generic competition, and standard ramipril capsules are established generic products. A new Paragraph IV dispute would be more likely to involve a newly developed ramipril formulation, fixed-dose combination, or delivery technology than the original ALTACE formulation.

The commercial screening question is therefore not whether a company can enter the basic ramipril capsule market. It is whether the proposed product can create clinically useful differentiation without triggering an unnecessary patent dispute or an avoidable bioequivalence burden.

What is the FDA regulatory status and Orange Book position of ALTACE?

ALTACE was approved by the FDA under NDA 019901. Ramipril is regulated as a conventional small-molecule prescription drug, not as a biologic. The principal regulatory pathways are:

1. An abbreviated new drug application for a bioequivalent generic capsule.
2. A 505(b)(2) application for a materially different formulation or route.
3. A full NDA for a new combination, delivery system, or clinically differentiated product.

The basic immediate-release capsule is suitable for an ANDA if the product demonstrates pharmaceutical equivalence and bioequivalence to the selected reference listed drug. A modified-release, pediatric, liquid, orally disintegrating, or device-enabled presentation may require a 505(b)(2) strategy.

Regulatory implications of excipient changes

A conventional generic can use different inactive ingredients if the formulation remains pharmaceutically equivalent and meets applicable safety, quality, and bioequivalence requirements. The development burden rises when the excipient change affects:

• Dissolution or release rate
• Ramipril degradation
• Powder-flow behavior
• Capsule fill uniformity
• Food effect
• Exposure to sensitive populations
• Stability under high humidity
• Labeling for allergies or dietary restrictions

The FDA’s inactive-ingredient framework and product-specific guidance should be reviewed during formulation development. [3,4]

How strong is the ALTACE patent estate?

The patent estate for unmodified ramipril capsules is weak from a market-exclusivity perspective because the foundational rights have expired. The stronger intellectual-property opportunities are formulation-specific.

Potentially patentable areas

Development area	Possible claim focus	Commercial strength
Moisture-protective capsule fill	Stabilized ramipril composition	Moderate if stability improvement is unexpected
Amorphous or engineered ramipril particles	Particle-size distribution, solid state, dissolution	Moderate
Oral liquid	Solubilized or suspension formulation with defined shelf life	Moderate to high if pediatric use is supported
Orally disintegrating tablet	Rapid disintegration and acceptable taste	Moderate
Fixed-dose combination	Ramipril with amlodipine, hydrochlorothiazide, or another cardiovascular agent	Moderate
Modified release	Once-daily pharmacokinetic profile or tolerability benefit	High development risk
Manufacturing process	Improved yield, impurity control, or continuous processing	Moderate, with limited blocking power
Device-enabled delivery	Dose tracking or adherence monitoring	Low to moderate unless technically distinctive

A patent on a routine excipient substitution is unlikely to provide durable protection. Stronger claims require a defined technical effect, such as materially improved stability, reduced impurity formation, improved bioavailability, or a clinically relevant dosing advantage.

What formulation patents could create commercial value?

Moisture- and oxidation-controlled capsules

Ramipril is susceptible to degradation pathways that can affect assay, impurity levels, and shelf life. A formulation using low-moisture excipients, protective packaging, desiccant integration, or a specialized capsule shell could reduce degradation.

Commercial value would depend on measurable performance:

• Longer shelf life
• Lower storage burden
• Fewer out-of-specification batches
• Improved stability in tropical markets
• Reduced packaging cost
• Fewer recalls or product complaints

A moisture-control strategy should avoid excipients that increase water activity or produce inconsistent capsule-fill behavior. The excipient supplier’s residual moisture specification may matter as much as the nominal excipient identity.

Oral liquid ramipril

An oral liquid could target pediatric, geriatric, dysphagia, and enteral-tube populations. The technical challenge is maintaining dose uniformity and chemical stability after reconstitution or during in-use storage.

Key formulation requirements include:

• Controlled ramipril hydrolysis
• Palatable taste
• Accurate measurement at low doses
• Compatibility with oral syringes and feeding tubes
• Preservative efficacy where required
• Defined beyond-use or in-use dating
• Low sedimentation or rapid redispersibility

Ramipril oral liquid development may support a 505(b)(2) route if the formulation has a meaningful clinical or administration advantage over capsules.

Orally disintegrating tablets

An orally disintegrating ramipril product could improve administration for patients who cannot swallow capsules. Excipients may include superdisintegrants, directly compressible fillers, taste-masking agents, and low-moisture processing aids.

The main commercial barriers are taste, dose uniformity at 1.25 mg, tablet friability, and the need to show that the product does not create clinically meaningful changes in exposure. A small-molecule ACE inhibitor is well suited to an ODT from a dose-load perspective, but the market must support a premium over low-cost generic capsules.

Fixed-dose combinations

Combination products create a more credible commercial opportunity than a simple excipient change. Potential combinations include:

• Ramipril plus amlodipine
• Ramipril plus hydrochlorothiazide
• Ramipril plus a statin or other cardiovascular agent
• Ramipril plus a diuretic for selected heart-failure populations

The commercial case is strongest where the combination reduces pill burden and aligns with guideline-based treatment. The regulatory pathway may involve an ANDA for an established combination or a 505(b)(2) or NDA for a new strength, dosage form, or indication.

What manufacturing and excipient barriers affect ramipril products?

Content uniformity at low strengths

The 1.25 mg strength creates a high risk of blend segregation and sampling variability. Development teams should prioritize:

• Geometric dilution or ordered mixing
• Narrow particle-size distributions
• Low-segregation excipient systems
• In-process blend-uniformity testing
• Robust encapsulation controls
• Validated stratified sampling

A formulation that performs well at 10 mg may not transfer directly to 1.25 mg.

Moisture management

Moisture can affect ramipril stability, capsule-shell behavior, powder flow, and dissolution. High-humidity markets create additional risk. Packaging may need high-barrier blister materials, foil-foil systems, or bottle-and-desiccant configurations.

Packaging can be part of the product strategy, but it is harder to secure broad patent protection for packaging alone unless it is integrated with a specific stability result.

Excipient supply and dual sourcing

A commercial formulation should use excipients available from at least two qualified suppliers where possible. Single-source risks include:

• Pregelatinized starch grade changes
• Microcrystalline cellulose variability
• Capsule-shell gelatin supply disruptions
• Colorant restrictions
• Regional differences in excipient monographs
• Changes in residual moisture or particle-size specifications

The formulation should be designed around functional specifications rather than a single vendor’s trade name.

How does ALTACE compare with competing ACE inhibitors?

Product	Active ingredient	Main dosage-form opportunity	Patent position	Commercial implication
ALTACE	Ramipril	Capsule, oral liquid, ODT, combination	Foundational rights expired	Generic price pressure; differentiation required
Vasotec	Enalapril	Tablet, oral solution, combination	Foundational rights expired	Larger generic familiarity and broad competition
Prinivil/Zestril	Lisinopril	Tablet, solution, ODT-style opportunities	Foundational rights expired	Strong generic substitution
Lotensin	Benazepril	Tablet, combination	Foundational rights expired	Smaller differentiated-product opportunity
Capoten	Captopril	Tablet, compounded liquid	Foundational rights expired	Older product with lower premium potential

Ramipril has a clinically recognized cardiovascular-risk-reduction profile, but that does not by itself support a formulation premium. Payers and pharmacies generally treat conventional ACE inhibitors as mature generic products. A new product must therefore offer a practical administration or adherence benefit.

What generic launch scenarios exist for ALTACE?

Scenario 1: Low-cost conventional capsule

This is the simplest route and has the lowest development risk. It also has the weakest pricing power. Success depends on manufacturing cost, supply reliability, wholesaler access, and the ability to obtain preferred generic placement.

Scenario 2: Authorized or branded generic

A branded generic can support stronger physician and pharmacy recognition but faces limited willingness to pay. Packaging, supply continuity, and channel strategy become more important than excipient differentiation.

Scenario 3: Specialty oral liquid

An oral liquid can target hospitals, pediatric pharmacies, long-term-care facilities, and patients with swallowing limitations. The addressable population is smaller, but pricing and switching resistance may be better than for capsules.

Scenario 4: Adherence-focused combination

A fixed-dose product can compete on reduced pill burden. The main barriers are clinical positioning, reimbursement, combination-dose selection, and regulatory requirements.

Scenario 5: Premium ODT

An ODT can target dysphagia and convenience. Commercial viability depends on whether the product receives coverage and whether patients or caregivers value the dosage form enough to offset generic substitution.

What revenue exposure does ALTACE represent?

ALTACE itself is a mature brand and does not offer the revenue profile of a protected, high-growth medicine. The economic opportunity lies in market segmentation rather than in recovering the original brand market.

Revenue potential can come from:

• High-volume commodity capsules with efficient production
• Hospital and long-term-care supply contracts
• Pediatric or dysphagia formulations
• Fixed-dose combinations
• Private-label or regional licensing
• Emerging-market supply where cardiovascular treatment access is expanding
• Manufacturing licenses for stabilized or lower-cost formulations

The conventional capsule market is likely to be price-driven. A differentiated formulation can command better economics only if it solves a documented problem and obtains reimbursement or institutional adoption.

Which companies are challenging or competing with ALTACE?

Competition is primarily from manufacturers of generic ramipril and other ACE inhibitors rather than from companies defending active ALTACE patents. The relevant competitive groups include:

• Large generic manufacturers
• Regional cardiovascular-focused pharmaceutical companies
• Contract development and manufacturing organizations
• Specialty companies developing pediatric or liquid dosage forms
• Combination-product developers
• Private-label suppliers to pharmacy and hospital channels

Because the active ingredient is old and widely characterized, manufacturing quality, cost, regulatory execution, and supply reliability are the main competitive variables.

What geographic opportunities exist for ramipril formulations?

The best geographic opportunities depend on dosage-form needs and regulatory complexity.

Region	Opportunity
United States	ANDA capsule competition; 505(b)(2) opportunity for differentiated dosage forms
European Union	Generic and hybrid applications; country-level pricing pressure
Japan	Regional formulation and aging-population opportunities
China	Generic competition and local procurement pressure
Latin America	Stable cardiovascular demand; supply and affordability are central
Middle East and Africa	Import substitution, hospital supply, and heat-stability advantages
Southeast Asia	Humidity-resistant packaging and affordable combination products

A tropical-stability formulation may have greater practical value in Southeast Asia, Latin America, Africa, and parts of the Middle East than in the United States. That advantage should be supported by accelerated and long-term stability data under relevant ICH conditions.

What is the commercial recommendation for an ALTACE excipient strategy?

The preferred development path is a tiered portfolio:

1. Use a conventional, low-cost capsule as the base product.
2. Develop a moisture-optimized version with dual-sourced excipients and high-barrier packaging.
3. Evaluate an oral liquid for pediatric, geriatric, and enteral-tube use.
4. Screen a fixed-dose combination only where clinical guidelines and reimbursement support pill-burden reduction.
5. Treat an ODT as a secondary option unless patient research confirms demand.
6. Avoid relying on a routine excipient substitution as the primary patent strategy.

The highest-value technical work is likely to involve stability, low-dose uniformity, and differentiated administration rather than novel pharmacology.

Key Takeaways

• ALTACE is ramipril, an established small-molecule ACE inhibitor with expired foundational patent and regulatory exclusivity.
• Conventional ramipril capsules are a low-margin generic opportunity.
• Excipient selection matters most for low-dose content uniformity, moisture control, dissolution, and manufacturing robustness.
• The strongest formulation opportunities are oral liquid, ODT, fixed-dose combination, and stability-enhanced capsule products.
• A routine excipient substitution is unlikely to create durable patent protection.
• A 505(b)(2) pathway may be appropriate for a materially differentiated dosage form.
• Commercial success will depend on reimbursement, supply reliability, manufacturing cost, and a demonstrated administration benefit.
• Geographic opportunities are strongest where humidity, dysphagia, pediatric dosing, or hospital supply constraints create a practical need.

FAQs

Is ramipril still protected by patents?

The foundational U.S. patents covering ramipril and the original ALTACE capsule have expired. New protection would need to arise from a patentable formulation, combination, manufacturing process, or delivery system.

Can an oral liquid ramipril product receive separate market protection?

Yes. A novel oral liquid may support patent claims and potentially a 505(b)(2) application if it demonstrates a differentiated formulation, stability profile, dosing benefit, or clinical-use advantage.

Which excipient is most important for low-dose ramipril capsules?

No single excipient controls performance. The most important variables are the complete powder system, particle-size distribution, mixing method, moisture level, and capsule-fill process.

Does ramipril require a biologic or biosimilar strategy?

No. Ramipril is a conventional synthetic small molecule. The relevant pathways are ANDA, 505(b)(2), or NDA, not biosimilar approval.

Can a new ramipril formulation avoid generic substitution?

Only if it has a distinct regulatory presentation, reimbursement position, or clinical-use advantage. A different excipient system alone generally will not prevent substitution unless it supports a separate legally protected product and market position.

References

1. U.S. Food and Drug Administration. (n.d.). ALTACE-ramipril capsule prescribing information. DailyMed. https://dailymed.nlm.nih.gov/

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

3. U.S. Food and Drug Administration. (1988). Inactive ingredient database. https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm

4. U.S. Food and Drug Administration. (2014). ANDA submissions: Generic drug user fee amendments guidance for industry. https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs