List of Excipients in Branded Drug ISOSORBIDE MONONITRATE

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Physicians Total Care Inc	ISOSORBIDE MONONITRATE	isosorbide mononitrate	54868-4478	ALUMINUM STEARATE
Physicians Total Care Inc	ISOSORBIDE MONONITRATE	isosorbide mononitrate	54868-4478	CELLULOSE, MICROCRYSTALLINE
Physicians Total Care Inc	ISOSORBIDE MONONITRATE	isosorbide mononitrate	54868-4478	LACTOSE
Physicians Total Care Inc	ISOSORBIDE MONONITRATE	isosorbide mononitrate	54868-4478	SILICON DIOXIDE

Generic Drugs Containing ISOSORBIDE MONONITRATE

Company	Ingredient	NDC	Excipient
Actavis Pharma Inc	isosorbide mononitrate	0228-2631	CALCIUM STEARATE
Actavis Pharma Inc	isosorbide mononitrate	0228-2631	CELLULOSE, MICROCRYSTALLINE
Actavis Pharma Inc	isosorbide mononitrate	0228-2631	FD&C BLUE NO. 1 ALUMINUM LAKE
Actavis Pharma Inc	isosorbide mononitrate	0228-2631	LACTOSE MONOHYDRATE

What are the Most Frequently-Used Excipients in ISOSORBIDE MONONITRATE?

# Of NDCs	Excipient
1	AMMONIUM PHOSPHATE, DIBASIC
1	ANHYDROUS LACTOSE
4	CALCIUM STEARATE
3	CARNAUBA WAX

Isosorbide Mononitrate Excipient Strategy and Commercial Opportunities

Last updated: August 5, 2026

Isosorbide mononitrate is a mature, multisource nitrate with limited active-ingredient patent protection and low formulation barriers for conventional immediate-release tablets. The strongest commercial opportunities are in modified-release performance, excipient differentiation, supply reliability, patient tolerability, and regulatory execution rather than new chemical entity exclusivity. A developer should prioritize robust once-daily extended-release tablets, lactose-free or low-excipient variants, and differentiated manufacturing controls over novel dosage forms with limited clinical value.

What is the commercial and regulatory status of isosorbide mononitrate?

Isosorbide mononitrate is an orally administered organic nitrate used primarily for the prevention of angina pectoris. It is available in immediate-release and extended-release tablets. The product is not generally used to terminate an acute angina attack because its onset and dosing profile are not suited to rapid rescue therapy.

The United States market is dominated by generic products and legacy branded extended-release products, including Imdur. FDA-approved products are regulated through abbreviated new drug applications for multisource versions and through legacy full applications for branded products.

Attribute	Commercial assessment
Active ingredient	Isosorbide mononitrate
Therapeutic class	Organic nitrate; antianginal
Principal dosage forms	Immediate-release and extended-release oral tablets
Main branded reference	Imdur extended-release tablets
Generic availability	Broad, established generic supply
Biologic risk	None; this is a small-molecule drug
Primary regulatory route	ANDA for generic products
Core development risk	Release-rate control, dose dumping, bioequivalence, stability
Patent environment	Mature product with limited practical patent barriers
Commercial growth profile	Low to moderate; driven by supply, price, formulation and channel execution

The FDA’s Orange Book identifies reference-listed drugs, approved generic equivalents and relevant patent or exclusivity information. For isosorbide mononitrate, commercial entry is generally governed more by ANDA requirements, manufacturing economics and product quality than by active compound patent exclusivity (FDA, n.d.-a).

When does isosorbide mononitrate lose exclusivity?

Isosorbide mononitrate has already passed its primary small-molecule patent and regulatory exclusivity period in the United States. The commercially relevant question is not whether the active ingredient remains protected, but whether a proposed product creates a meaningful formulation, manufacturing or market-access advantage.

Legacy brand protection for extended-release products may have included formulation or method-of-use patents. Those protections are distinct from active-ingredient protection. A current applicant must review the Orange Book patent listing for the relevant reference product and assess whether any listed patent remains unexpired or legally relevant at the time of ANDA filing.

Exclusivity timeline

Period	Strategic significance
Initial branded development	Protection centered on the active ingredient, clinical development and formulation
Generic entry period	ANDA applicants could rely on reference-product data
Mature generic period	Price competition and manufacturing reliability became the main barriers
Current market	Differentiation depends on dosage form, excipient profile, supply assurance and customer access

There is no biosimilar pathway for isosorbide mononitrate. Biosimilar risk is therefore not applicable. Competitive pressure comes from generic tablets, alternative nitrates and other antianginal therapies rather than biosimilar substitution.

What patents protect isosorbide mononitrate products?

The active ingredient is not the principal source of current exclusivity. Any remaining intellectual-property value is more likely to arise from:

• Extended-release matrix design.
• Tablet geometry and manufacturing process.
• Release-rate control.
• Specific excipient combinations.
• Methods of reducing adverse effects or improving adherence.
• Packaging or device-related features, where applicable.
• Manufacturing know-how that is not publicly disclosed.

A generic applicant should separate three categories of rights:

1. Orange Book-listed patents. These can trigger a Paragraph IV certification or a section viii statement, depending on the claimed use.
2. Unlisted formulation or process patents. These may create litigation risk but do not automatically block ANDA approval.
3. Trade secrets and manufacturing know-how. These can impede rapid replication without appearing in public patent databases.

What is the Orange Book status of isosorbide mononitrate?

The Orange Book should be reviewed by active ingredient, dosage form, strength and reference product. The relevant records are expected to include immediate-release and extended-release tablet products, with the most important reference-product analysis focused on Imdur and its generic equivalents.

A launch assessment should document:

Review item	Required analysis
Reference-listed drug	Confirm NDA, strength and dosage form
Listed patents	Identify expiration dates and patent-use codes
Exclusivity	Confirm whether any regulatory exclusivity remains
Generic approvals	Map approved ANDAs by strength and dosage form
Certification strategy	Determine Paragraph IV, Paragraph III or section viii position
Litigation	Search federal court filings and FDA patent-certification notices
Label scope	Confirm whether proposed labeling matches the reference product

Because this is a mature product, a Paragraph IV filing would generally be relevant only if a listed patent remained active. A formulation developer should not assume that the absence of an active ingredient patent eliminates all litigation risk.

What excipients are used in isosorbide mononitrate tablets?

Immediate-release tablets typically use conventional solid-dose excipients. The formulation objective is rapid disintegration, content uniformity and mechanical strength.

Common excipient categories include:

• Lactose or another soluble diluent.
• Microcrystalline cellulose.
• Pregelatinized starch or other binder/disintegrant.
• Povidone where granulation requires additional binding.
• Colloidal silicon dioxide as a glidant.
• Magnesium stearate as a lubricant.
• Film-coating polymers, pigments and plasticizers.

Extended-release products require a different design. The excipient system must control drug release over the intended dosing interval while preventing dose dumping. Hydrophilic matrix polymers, insoluble polymers, pore-forming agents and compression-control materials are possible tools. Exact composition varies by manufacturer and may be protected through formulation patents or confidential know-how.

FDA labeling and DailyMed records should be used to verify the inactive-ingredient profile of each approved product rather than relying on a generic formulation assumption (FDA, n.d.-b; National Library of Medicine, n.d.).

What excipient strategy is best for immediate-release tablets?

The lowest-risk strategy is a conventional, direct-compression or dry-granulation platform using well-characterized excipients with established pharmaceutical use.

Preferred design objectives

Objective	Excipient strategy
Fast disintegration	Use a reliable superdisintegrant or starch-based system
Low dose uniformity risk	Improve blend homogeneity and minimize segregation
Tablet strength	Use microcrystalline cellulose or a suitable binder
Manufacturing throughput	Favor direct compression if powder flow permits
Stability	Control moisture and avoid unnecessary hygroscopic excipients
Patient differentiation	Consider lactose-free and low-allergen positioning
Cost control	Limit custom polymers and complex processing

Isosorbide mononitrate is generally formulated at strengths that permit conventional tablet manufacturing. The main technical issue is not high-dose loading but consistent drug distribution and release. Blend segregation can become material when particle size, density or morphology differs substantially between the active ingredient and excipients.

A lactose-free formulation could address patients with lactose intolerance, although the clinical value must be assessed carefully because the amount of lactose in a tablet may be small. It can still have commercial value in institutional formularies, tenders and markets where excipient declarations influence procurement.

What formulations are protected by extended-release excipients?

Extended-release tablets offer the clearest formulation opportunity. The reference product uses a controlled-release approach that supports once-daily dosing. An applicant can pursue a conventional hydrophilic matrix, an insoluble matrix, a multiparticulate system or another release-controlling platform, but the regulatory burden increases as the formulation departs from the reference product.

Formulation options

Platform	Commercial benefit	Main risk
Hydrophilic matrix tablet	Low manufacturing complexity and scalable production	Polymer hydration and food-effect variability
Insoluble matrix tablet	Strong release control and mechanical durability	Incomplete release and process sensitivity
Coated controlled-release tablet	Adjustable release profile	More manufacturing steps and coating variability
Multiparticulate capsule	Flexible release engineering	Higher unit cost and encapsulation complexity
Orally disintegrating tablet	Potential swallowing benefit	Difficult compatibility with prolonged release
Abuse-deterrent or specialized platform	Possible niche value	Weak commercial rationale for this molecule

The most defensible strategy is usually an extended-release tablet with a simple matrix system, supported by comparative dissolution, food-effect work and bioequivalence testing. A novel platform should be pursued only if it solves a specific problem such as swallowing difficulty, reduced variability or improved adherence.

Key excipient variables

• Polymer viscosity grade.
• Polymer concentration.
• Drug-to-polymer ratio.
• Tablet porosity.
• Compression force.
• Lubrication time.
• Granule moisture.
• Coating weight, if coated.
• Dissolution behavior across pH conditions.
• Sensitivity to alcohol exposure.

Extended-release nitrate products require careful evaluation for alcohol-induced accelerated release. The FDA has treated dose-dumping risk as a material issue for modified-release products, making alcohol robustness and dissolution method development central to the regulatory package (FDA, 2019).

How can manufacturers differentiate isosorbide mononitrate products?

A generic product can be differentiated without relying on a new active ingredient patent.

Commercially credible opportunities

1. Once-daily extended-release supply. Consistent availability can matter more than minor formulation novelty in a mature generic market.
2. Lactose-free tablets. This can support institutional and international procurement.
3. Smaller tablets. Tablet dimensions can improve adherence, although the commercial effect is patient-segment specific.
4. Scored tablets. Scoring may support dose adjustment, but it must be validated for dose uniformity and mechanical performance.
5. Low-dust manufacturing. This can improve worker safety and production controls.
6. High-quality packaging. Moisture protection and clear labeling reduce stability and dispensing problems.
7. Multiple strengths. A coordinated strength portfolio can improve formulary access.
8. Regional supply security. Dual sourcing of the active ingredient and critical excipients can support tender competitiveness.
9. Contract manufacturing. A reliable finished-dose platform may be attractive to regional pharmaceutical companies without internal modified-release capabilities.

The commercial value of an excipient change depends on whether it produces a measurable benefit. A reformulation that changes only the inactive-ingredient list but does not improve tolerability, stability, manufacturing yield or market access is unlikely to support premium pricing.

What manufacturing and intellectual-property barriers exist?

The active pharmaceutical ingredient is commercially available, but quality and supply continuity remain relevant. Potential barriers include:

• API particle-size variability.
• Nitrosamine and impurity-control requirements applicable to the supply chain.
• Sensitivity of dissolution to granulation and compression conditions.
• Polymer lot-to-lot variability.
• Lubricant overmixing and delayed dissolution.
• Moisture-related stability changes.
• Limited availability of qualified suppliers for specialized excipients.
• Scale-up differences between pilot and commercial compression equipment.

Manufacturing know-how can be more valuable than a narrow formulation patent. A company with a robust extended-release process, validated dissolution method and stable supply chain may compete effectively even without broad patent protection.

Process patents may cover granulation, compression, coating or release control. Their commercial usefulness depends on claim scope, enforceability, remaining term and the availability of non-infringing alternatives. For a mature generic, process design-around is often feasible, but the regulatory and scale-up cost can still be significant.

Which companies are challenging isosorbide mononitrate products?

The competitive field is primarily composed of generic manufacturers and legacy branded-product suppliers. There is no biosimilar competition because isosorbide mononitrate is a small molecule.

Competition is likely to arise through:

• ANDA-approved immediate-release tablets.
• ANDA-approved extended-release tablets.
• Authorized generic arrangements.
• Regional manufacturers selling outside the United States.
• Private-label products supplied through contract manufacturers.
• Alternative antianginal therapies, including other nitrate products and non-nitrate agents.

A company evaluating entry should map approved suppliers by strength, dosage form, manufacturing site and shortage history. The number of ANDA holders alone does not show whether the market is crowded. A market with several nominal suppliers can still have concentration if only a few maintain consistent commercial inventory.

What patent litigation affects isosorbide mononitrate?

The most important litigation question is whether an ANDA applicant challenges an active Orange Book-listed patent for an extended-release reference product. If no relevant listed patent remains active, litigation exposure shifts to:

• Unlisted patents.
• Trade-secret disputes.
• Manufacturing-process claims.
• Product liability.
• Regulatory disputes over bioequivalence or labeling.
• Contract and supply disagreements.

A Paragraph IV challenge could create a 30-month stay if statutory conditions are met after the reference-product sponsor receives the certification notice. The commercial value of that challenge would depend on the remaining patent term, the likelihood of an injunction and the size of the addressable market.

Because isosorbide mononitrate is a low-growth generic, litigation economics are usually weaker than for high-revenue medicines. A patent challenge is most attractive when the product has constrained supply, high gross margins or a reference product with meaningful remaining market share.

What generic launch risks exist for isosorbide mononitrate?

The primary launch risks are regulatory and commercial.

Regulatory risks

• Failure to match the reference release profile.
• Food-effect differences.
• Dose dumping under alcohol conditions.
• Inadequate stability data.
• Tablet-splitting or scoring problems.
• Labeling differences.
• Inactive-ingredient safety concerns.
• Manufacturing-site deficiencies.
• Failure to demonstrate batch-to-batch dissolution consistency.

Commercial risks

• Low unit price.
• High wholesaler and pharmacy substitution pressure.
• Limited brand loyalty.
• Established generic competitors.
• Small market size for individual strengths.
• Procurement concentration.
• Inventory write-offs from tender losses.
• Dependence on a single API or polymer supplier.

A low-cost immediate-release product may have limited value unless the manufacturer has an efficient supply chain. An extended-release product can achieve better positioning, but it requires more development work and has a higher risk of bioequivalence failure.

How does isosorbide mononitrate compare with competing antianginal drugs?

Product category	Patent position	Formulation opportunity	Commercial profile
Isosorbide mononitrate	Mature and largely generic	Extended release, excipient differentiation	Low-growth, price-sensitive
Isosorbide dinitrate	Mature generic	Immediate-release and combination products	Competitive, clinically differentiated by dosing
Nitroglycerin	Mature but dosage-form diverse	Sublingual, transdermal and topical delivery	More dosage-form complexity
Beta blockers	Mature generic	Modified release and combination products	Larger competitive class
Calcium-channel blockers	Mature generic	Extended release and fixed-dose combinations	Broader indications and higher volume
Ranolazine	Newer relative to nitrate products	Extended release and formulation control	Greater value per product, more complex IP history

Isosorbide mononitrate offers fewer high-value delivery opportunities than nitroglycerin because its principal use is preventive rather than rescue therapy. Its advantage is development simplicity, not high technological differentiation.

What licensing deals are commercially viable?

Licensing opportunities are most credible in finished-dose rights, regional commercialization and manufacturing technology.

Potential structures include:

• Regional license for an approved extended-release product.
• Supply-and-license agreement with a contract manufacturer.
• Private-label distribution agreement.
• Technology transfer for a controlled-release matrix.
• Co-development of a lactose-free or low-excipient product.
• Dual-source supply agreement for public tenders.
• Acquisition of an ANDA or approved product portfolio.

An active-ingredient license is unlikely to create significant value because the molecule is off-patent and widely available. The stronger transaction targets are approved regulatory files, reliable manufacturing capacity and differentiated market access.

What is the revenue exposure and market-entry case?

Isosorbide mononitrate is unlikely to support a large premium-priced franchise. Revenue exposure depends on volume, channel, geography and product mix.

A commercial model should calculate:

• Annual tablets sold by strength.
• Generic net price.
• Wholesaler and pharmacy deductions.
• Tender pricing.
• Manufacturing cost per tablet.
• API cost and yield.
• Polymer and coating costs.
• Batch-release and stability costs.
• Regulatory maintenance cost.
• Expected substitution rate.
• Supply interruption probability.

Attractive entry conditions

Entry is more compelling where:

• Existing suppliers have recurring shortages.
• Extended-release products are concentrated among few manufacturers.
• Regional tenders reward supply continuity.
• A local company lacks a qualified controlled-release platform.
• The developer can use an existing tablet and coating facility.
• A differentiated excipient profile supports formulary or patient access.

Entry is less compelling where the target market has many reliable suppliers, aggressive price erosion and no meaningful supply constraint.

How strong is the patent estate for isosorbide mononitrate?

The patent estate is weak for the active ingredient and potentially moderate for specific extended-release implementations. Strength should be assessed claim by claim rather than by counting historical patents.

IP layer	Relative strength
Active ingredient	Low
Basic immediate-release tablet	Low
Extended-release formulation	Potentially moderate
Manufacturing process	Variable
Method of use	Usually limited commercial blocking value
Trade secrets	Potentially important
Regulatory file and market access	Practical value can exceed patent value

A developer should avoid building its business case around broad exclusion. The defensible asset is more likely to be a low-cost, technically reliable product with strong manufacturing economics.

Key Takeaways

• Isosorbide mononitrate is a mature generic small molecule with no biosimilar risk.
• Active-ingredient exclusivity is no longer the principal commercial issue.
• Extended-release tablets offer the strongest formulation opportunity.
• Hydrophilic matrix systems provide a practical development platform.
• Dissolution, food effect, alcohol robustness and dose uniformity are central regulatory risks.
• Lactose-free, smaller, scored or supply-secure products may support targeted differentiation.
• Patent risk is concentrated in formulation, process and unlisted rights rather than the molecule itself.
• Licensing value is strongest in approved products, regional rights and manufacturing technology.
• Commercial success depends on cost, supply reliability, tender access and product quality.
• A conventional immediate-release product is easy to develop but difficult to differentiate; an extended-release product is more defensible but carries greater development risk.

FAQs

Is isosorbide mononitrate suitable for an orally disintegrating tablet?

An orally disintegrating tablet is technically possible, but its commercial value is limited unless it improves swallowing, adherence or access for a defined patient group. The product is used for prevention, so rapid disintegration does not automatically create a clinically meaningful advantage.

Can an excipient change create new patent protection for isosorbide mononitrate?

A new excipient combination may support patent claims if it produces a non-obvious and reproducible technical effect, such as a distinct release profile or improved stability. A simple substitution of lactose, starch or lubricant is unlikely to create strong patent protection.

What is the most attractive isosorbide mononitrate product opportunity?

A robust once-daily extended-release tablet with reliable dissolution, competitive cost and a differentiated excipient profile is generally more attractive than another standard immediate-release tablet.

Does isosorbide mononitrate require a food-effect study?

Extended-release products generally require assessment of food effects as part of comparative pharmacokinetic and bioequivalence development. The exact study design depends on the reference product and applicable FDA guidance.

Can isosorbide mononitrate be combined with other active ingredients?

Fixed-dose combinations are possible, but they create additional regulatory and formulation complexity. The commercial rationale must justify compatibility, dosing alignment, stability and clinical or adherence benefits.

References

1. U.S. Food and Drug Administration. (2019). The Use of Physiologically Based Pharmacokinetic Analyses: Biopharmaceutics Applications for Oral Drug Product Development, Manufacturing Changes, and Regulatory Submission. FDA.

2. U.S. Food and Drug Administration. (n.d.-a). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. FDA.

3. U.S. Food and Drug Administration. (n.d.-b). Inactive ingredient database. FDA.

4. National Library of Medicine. (n.d.). DailyMed: Current medication information. U.S. National Library of Medicine.

5. 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. FDA.