List of Excipients in Branded Drug RANOLAZINE

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Generic Drugs Containing RANOLAZINE

Company	Ingredient	NDC	Excipient
NCS HealthCare of KY LLC dba Vangard Labs	ranolazine	0615-8569	CELLULOSE, MICROCRYSTALLINE
NCS HealthCare of KY LLC dba Vangard Labs	ranolazine	0615-8569	HYPROMELLOSE 2910
NCS HealthCare of KY LLC dba Vangard Labs	ranolazine	0615-8569	MAGNESIUM STEARATE
NCS HealthCare of KY LLC dba Vangard Labs	ranolazine	0615-8569	METHACRYLIC ACID AND ETHYL ACRYLATE COPOLYMER
NCS HealthCare of KY LLC dba Vangard Labs	ranolazine	0615-8569	POLYETHYLENE GLYCOL 4000

What are the Most Frequently-Used Excipients in RANOLAZINE?

# Of NDCs	Excipient
1	CARMINIC ACID
2	CARNAUBA WAX
44	CELLULOSE, MICROCRYSTALLINE
1	D&C YELLOW NO. 10
1	FD&C BLUE NO. 1

Ranolazine Excipient Strategy and Commercial Opportunities

Last updated: September 24, 2026

Ranolazine is an immediate-release and extended-release antianginal with the strongest commercial opportunity in differentiated oral formulations, generic lifecycle management, and cost-efficient manufacturing. The originator product, Ranexa, uses extended-release tablets containing 500 mg or 1,000 mg of ranolazine. The principal formulation challenge is controlled drug release from a high-dose tablet while maintaining consistent dissolution, tablet integrity, and bioavailability.

Ranolazine has limited current biologic, device, or biosimilar exposure. Commercial competition is primarily among generic extended-release tablets. The original composition and controlled-release patent estate has largely expired, shifting value from basic molecule protection to formulation performance, manufacturing reliability, regulatory status, and market access.

What is ranolazine and how is it commercialized?

Ranolazine is approved for the treatment of chronic angina. The FDA-approved product is Ranexa extended-release tablets, originally developed and commercialized by CV Therapeutics and later acquired by Gilead Sciences. The FDA approved Ranexa in 2006 under NDA 021526. The product is available in 500 mg and 1,000 mg extended-release strengths.[1]

Attribute	Ranolazine
Active ingredient	Ranolazine
Reference product	Ranexa
Dosage form	Extended-release tablet
Strengths	500 mg and 1,000 mg
Original sponsor	CV Therapeutics
Subsequent owner	Gilead Sciences
FDA approval	2006
Therapeutic area	Chronic angina
Primary commercial competition	Generic extended-release tablets
Biosimilar relevance	None
Key formulation issue	Controlled release of a high-dose drug

Ranolazine is generally administered twice daily. The FDA label recommends an initial dose of 500 mg twice daily, with escalation to 1,000 mg twice daily when clinically necessary and tolerated.[2]

The product has an important interaction profile. Ranolazine is primarily metabolized by CYP3A and is also a substrate of P-glycoprotein. It can inhibit CYP2D6 and prolong the QT interval in a dose-related manner.[2] These characteristics make dose dumping, excessive exposure, and dissolution variability important development and quality risks.

What excipients are used in ranolazine extended-release tablets?

Public product information identifies Ranexa as an extended-release tablet, but commercial formulations may use different excipient systems. Generic manufacturers are not required to copy every excipient used by the reference product. They must demonstrate pharmaceutical equivalence and bioequivalence under FDA requirements.

A practical ranolazine excipient platform would normally combine:

Formulation function	Candidate excipient classes	Commercial purpose
Matrix formation	Hypromellose, polyethylene oxide, polymeric cellulose derivatives	Controls drug diffusion and tablet erosion
Dilution	Microcrystalline cellulose, lactose, mannitol, dibasic calcium phosphate	Supports tablet weight and content uniformity
Binding	Povidone, copovidone, pregelatinized starch	Improves granule and tablet strength
Lubrication	Magnesium stearate, sodium stearyl fumarate	Controls ejection force
Flow improvement	Colloidal silicon dioxide	Improves powder flow and die filling
Film coating	Hypromellose, polyethylene glycol, titanium dioxide, iron oxides	Protects tablet and distinguishes strengths
pH or microenvironment control	Selected organic acids, carbonates, or buffering agents	Can modify dissolution and local drug solubility

The strongest excipient opportunity is an extended-release matrix that provides a reproducible dissolution profile across manufacturing lots. The objective is not simply to slow release. The formulation must control the early release phase, avoid dose dumping, resist mechanical damage, and maintain performance after exposure to gastrointestinal fluids.

Which excipients are most attractive for ranolazine?

Hypromellose is a commercially established option for hydrophilic matrix systems. Polymer grade, viscosity, particle size, substitution pattern, and concentration can materially affect the release curve. A high-viscosity grade may reduce erosion and diffusion, but it can also increase tablet size, compression sensitivity, and manufacturing cost.

Polyethylene oxide can provide strong gel formation and sustained release. Its use may require tighter control of raw-material variability and processing conditions. It may also create challenges in granulation, lubrication, and tablet disintegration.

Microcrystalline cellulose is attractive for direct compression and robust tablet manufacture. It can improve compactability but may alter liquid penetration and matrix erosion. Lactose and other soluble fillers can increase water ingress and potentially accelerate drug release.

Sodium stearyl fumarate can be evaluated where magnesium stearate produces excessive hydrophobicity or dissolution sensitivity. The selection must be linked to blend time, compression force, ejection behavior, and dissolution performance.

What formulation patents protect ranolazine?

The principal historical patent value was associated with controlled-release ranolazine formulations rather than the active ingredient alone. Representative U.S. patents associated with ranolazine and extended-release technology include the following:

Patent	Subject matter	Historical relevance	Status
U.S. Patent No. 5,506,229	Ranolazine-related pharmaceutical compositions and use	Early ranolazine protection	Expired
U.S. Patent No. 6,303,640	Controlled-release ranolazine formulation	Core extended-release protection	Expired
U.S. Patent No. 6,852,724	Additional controlled-release ranolazine technology	Formulation and release protection	Expired
Ranexa Orange Book listings	Approved product, formulation, and method-of-use claims	Generic certification framework	Historical listings require current Orange Book confirmation

The core commercial issue is that expired controlled-release patents no longer provide the same exclusionary position as an active formulation patent. A new sponsor could still obtain patent protection for a genuinely differentiated excipient system, manufacturing process, multiparticulate dosage form, or abuse-resistant delivery system. The claims would need to distinguish over known ranolazine matrices and demonstrate a measurable technical effect.

Potentially protectable subject matter includes:

• A specific polymer ratio that produces a defined release profile.
• A multilayer tablet with separate immediate-release and extended-release zones.
• A multiparticulate capsule containing coated ranolazine pellets.
• A formulation with reduced food effect.
• A low-friability, high-drug-load tablet.
• A process that reduces content uniformity failures.
• A formulation that improves stability under high humidity.
• A once-daily dosage form, if clinical exposure and safety support the claim.
• A pediatric or liquid-compatible dosage form.
• A combination product using ranolazine with another antianginal or cardiovascular agent.

Patentability depends on claim scope, prior art, clinical relevance, and whether the formulation produces an unexpected result. A patent directed only to routine substitution of one diluent for another would face a weak obviousness position.

When did ranolazine lose exclusivity?

Ranolazine’s five-year new chemical entity exclusivity followed the 2006 FDA approval and generally ended in 2011. The principal extended-release patent barriers extended beyond regulatory exclusivity but have since expired or reached the end of their relevant enforceable terms.

Event	Approximate timing
Ranexa FDA approval	January 2006
NCE exclusivity period	Approximately through January 2011
Generic development and Paragraph IV activity	Primarily during the 2010s
Generic extended-release competition	Emerged after resolution of patent barriers
Current market position	Mature generic market

The exact launch timing for each generic depends on ANDA approval, litigation settlements, authorized-generic strategy, supply arrangements, and commercial decisions by individual applicants. FDA’s Orange Book remains the controlling source for current listed patents and exclusivity data.[3]

What is the Orange Book status of Ranexa?

The Orange Book identifies FDA-approved products, therapeutic equivalence information, patents submitted by NDA holders, and applicable exclusivity periods.[3] Ranexa’s key regulatory significance is its extended-release dosage form. Generic applicants must demonstrate equivalence to the reference listed drug rather than merely show that ranolazine is present in the same strength.

For ranolazine extended-release tablets, an ANDA applicant must address:

1. Same active ingredient and dosage form.
2. Same strength or approved equivalent strength.
3. Pharmaceutical equivalence.
4. Bioequivalence.
5. Comparable release behavior.
6. Appropriate labeling.
7. Certification against listed patents under Hatch-Waxman rules.

A Paragraph IV certification would assert that a listed patent is invalid, unenforceable, or not infringed. Historical Paragraph IV litigation around Ranexa focused on the scope and enforceability of extended-release and method-of-use patents. With the core patent estate expired, new applicants face less patent risk than they would have faced during the original generic challenge period.

Which companies are challenging ranolazine exclusivity?

Ranolazine generic competition has involved ANDA applicants and established generic manufacturers. The market has included major companies such as Teva, Actavis or Watson, Sandoz, Lupin, and other FDA-approved generic suppliers at different points in the product’s commercial history. The relevant competitive set changes as approvals, supply agreements, discontinuations, and private-label arrangements change.

The commercial importance of a Paragraph IV challenge is highest when:

• The applicant is first to file.
• The applicant obtains 180-day exclusivity.
• The challenged patent has a long remaining term.
• The product has high annual sales.
• The generic can launch without a settlement restriction.

For ranolazine, the value of first-filer status has declined with the maturity of the market. Manufacturing cost, wholesaler access, supply continuity, and contracted pricing now have greater influence on returns.

What excipient strategies create commercial opportunities?

Low-cost generic extended-release tablets

The most direct opportunity is a robust, low-cost tablet using a conventional hydrophilic matrix. The formulation should minimize dependence on narrow granulation endpoints and expensive specialized excipients. A direct-compression process can reduce capital requirements, but high ranolazine loading may require careful control of flow, segregation, and compression.

Smaller tablets

Ranolazine tablets contain a high dose, particularly at 1,000 mg. A smaller tablet could offer a practical commercial advantage if it maintains equivalent release and mechanical performance. Strategies include higher-density fillers, optimized granulation, multilayer compression, or reduced coating weight.

Tablet-size reduction is commercially relevant for patients taking multiple cardiovascular medicines. It can also reduce packaging volume and shipping costs.

Once-daily delivery

A once-daily formulation would have significant commercial value if it can maintain therapeutic exposure without increasing peak concentration or QT-related risk. The technical burden is high. A longer release profile must account for gastric transit, intestinal release, food effects, and ranolazine’s nonlinear exposure characteristics.

A once-daily product would likely require a new clinical and regulatory strategy rather than a simple generic substitution. It could support a 505(b)(2) application if the sponsor relies partly on the Ranexa safety and efficacy package while introducing a materially different dosage form.[4]

Abuse-resistant or tamper-resistant delivery

Abuse resistance is less central for ranolazine than for opioids or stimulants. A tamper-resistant design may still provide differentiation, but the commercial return is unlikely to justify substantial development expense unless paired with another benefit such as controlled release, reduced dose dumping, or improved stability.

Multiparticulate formulations

Pellets or coated granules in a capsule can provide more uniform gastrointestinal distribution than a single matrix tablet. Multiparticulates may reduce sensitivity to tablet fracture and permit flexible release engineering. The drawbacks are higher manufacturing complexity, more demanding coating controls, and potentially higher cost.

Pediatric and dysphagia-friendly dosage forms

A granule, sprinkle, orally disintegrating, or liquid-compatible product could expand use in patients who cannot swallow large tablets. Ranolazine’s high dose and taste profile create major formulation constraints. Taste masking, dose uniformity, and controlled release after dispersion would require substantial development work.

Stability-focused formulations

A formulation that improves moisture stability, reduces degradation, or permits less expensive packaging could create value in markets with high humidity and weak cold-chain infrastructure. Blister packaging, desiccant systems, and moisture-barrier coatings may be more economical than a new excipient system.

How strong is the ranolazine patent estate?

The current estate is weak for basic ranolazine products because the molecule and foundational extended-release protections are historically mature. The stronger opportunity is new intellectual property built around a measurable formulation or process advantage.

IP category	Relative strength today	Commercial assessment
Ranolazine molecule	Low	Basic protection expired
Conventional extended-release tablet	Low to moderate	Crowded prior art
Novel polymer architecture	Moderate	Patentable if technically differentiated
Once-daily formulation	Moderate to high	Requires clinical and PK support
Multiparticulate delivery	Moderate	Higher development cost
Manufacturing process	Moderate	Useful for supply and cost control
New method of use	Variable	Depends on clinical evidence
Combination therapy	Variable	Requires regulatory and patent strategy

A new patent portfolio should combine formulation claims, composition-of-matter claims directed to specific dosage forms, manufacturing claims, dissolution-profile claims, and method-of-use claims where supported. A single excipient substitution is unlikely to create durable exclusivity.

What FDA regulatory pathways apply to new ranolazine products?

A conventional generic extended-release tablet would normally use the ANDA pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act. The applicant must establish bioequivalence to the reference listed drug.[4]

A materially modified product may use the 505(b)(2) pathway. This route is more suitable for:

• New dosage forms.
• New release profiles.
• New strengths.
• New routes of administration.
• New combinations.
• Formulations with supporting clinical or pharmacokinetic differences.

A 505(b)(2) product may obtain three years of exclusivity for certain new clinical investigations, but the scope depends on the approval basis and the studies relied on. It does not recreate the original five-year NCE exclusivity for an old active ingredient.

What generic entry risks exist for ranolazine?

Generic entry risk is high because:

• The active ingredient is well established.
• The reference product is an oral solid dosage form.
• The principal use is already approved.
• Core patents have reached the end of their terms.
• Multiple generic manufacturers can manufacture extended-release tablets.
• The product does not require a complex device or biologic manufacturing process.

The main barriers are technical rather than legal. These include:

• Achieving bioequivalence with a high-dose extended-release tablet.
• Controlling release after tablet subdivision or mechanical damage.
• Managing food-related changes in exposure.
• Maintaining dissolution across pH conditions.
• Avoiding manufacturing-scale variability.
• Meeting commercial price targets.

What is the revenue opportunity for ranolazine reformulation?

Ranolazine reformulation is unlikely to support a premium solely through a cosmetic change. The strongest revenue opportunities are linked to a specific clinical or economic benefit:

1. Once-daily dosing.
2. Smaller tablets.
3. Lower tablet burden.
4. Improved tolerability through exposure control.
5. Stable performance under variable food conditions.
6. Pediatric or dysphagia-friendly administration.
7. Lower manufacturing cost.
8. Supply to emerging markets and institutional tenders.

The commercial ceiling for a new product is constrained by generic pricing. A sponsor should therefore prioritize development concepts that either expand the treated population or reduce total treatment burden. A conventional me-too extended-release tablet is more likely to compete on cost than on brand premium.

How does ranolazine compare with competing antianginal products?

Ranolazine differs from beta blockers, calcium-channel blockers, and long-acting nitrates because it can reduce angina without relying primarily on heart-rate or blood-pressure reduction. That positioning may support use in patients whose symptoms persist despite conventional therapy or who cannot tolerate further hemodynamic effects.[2]

Product class	Main commercial differentiator	Generic pressure	Formulation opportunity
Ranolazine	Metabolic antianginal mechanism	High	Extended release, smaller tablet, once daily
Beta blockers	Heart-rate reduction	Very high	Mostly low-value reformulation
Calcium-channel blockers	Vasodilation and rate control	High	Combination products
Long-acting nitrates	Vasodilation	Very high	Tolerance-management formulations
Ivabradine, where approved	Heart-rate reduction	Variable by market	Modified release and combination products

Ranolazine’s differentiation is clinically meaningful, but the product competes in a mature chronic cardiovascular market. Commercial success depends on adherence, physician familiarity, formulary status, and price.

What litigation and settlement issues affect ranolazine?

Historical Ranexa litigation centered on generic certifications and the validity or infringement of listed patents. Settlement agreements in branded-generic litigation can delay launch, authorize entry on a specified date, or establish supply and licensing terms. The commercial impact depends on the settlement date, first-filer rights, authorized-generic plans, and whether the agreement is subject to Federal Trade Commission review.

For current diligence, the controlling documents are:

• FDA Orange Book patent listings.
• ANDA litigation docket records.
• FDA approval letters.
• Paragraph IV notices.
• Settlement filings and FTC review materials.
• Commercial launch announcements.

The legal risk for a new ranolazine product is now more likely to arise from newly filed formulation patents than from the original Ranexa estate.

Key Takeaways

• Ranolazine’s principal formulation challenge is controlled release from a high-dose tablet.
• Hydrophilic polymer matrices, particularly hypromellose-based systems, are the most practical starting point.
• The foundational ranolazine and Ranexa extended-release patent estate is mature and largely expired.
• Generic entry risk is high, while biosimilar risk is not applicable.
• The best formulation opportunities are once-daily dosing, smaller tablets, multiparticulates, improved stability, and patient-friendly administration.
• A conventional generic is likely to compete on manufacturing cost and supply reliability.
• A differentiated reformulation would likely require a 505(b)(2) strategy and new clinical or pharmacokinetic evidence.
• New patent value is most likely in specific polymer architectures, release profiles, manufacturing processes, and clinically meaningful dosage-form improvements.

FAQs

Is ranolazine a high-solubility or low-solubility formulation target?

Ranolazine presents formulation challenges associated with limited and pH-dependent solubility, making release control and dissolution robustness important development variables.

Can ranolazine be formulated as a once-daily tablet?

Yes, a once-daily product is technically possible, but it would require control of exposure over an extended interval and likely additional pharmacokinetic and clinical support.

Are ranolazine excipient patents still commercially valuable?

They can be valuable when directed to a specific, non-obvious composition that produces a measurable release, stability, bioavailability, or manufacturing benefit. Routine excipient substitutions have weaker patent value.

Does ranolazine have biosimilar competition?

No. Ranolazine is a small-molecule drug, so competition occurs through generic drug applications rather than biosimilar applications.

What is the most attractive ranolazine product opportunity?

A smaller, robust extended-release tablet with improved adherence and low manufacturing cost is the most practical opportunity. A once-daily or patient-friendly formulation has greater upside but materially higher regulatory and clinical risk.

References

1. U.S. Food and Drug Administration. (2006). Ranexa approval letter and prescribing information, NDA 021526.
2. U.S. Food and Drug Administration. (2023). Ranexa (ranolazine) extended-release tablets prescribing 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). Guidance for industry: Bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA.
5. U.S. Patent and Trademark Office. (n.d.). Patent documents for ranolazine and controlled-release ranolazine formulations.