List of Excipients in Branded Drug DILATRATE

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Endo Pharmaceuticals Inc	DILATRATE	isosorbide dinitrate	52244-920	D&C RED NO. 33
Endo Pharmaceuticals Inc	DILATRATE	isosorbide dinitrate	52244-920	D&C YELLOW NO. 10
Endo Pharmaceuticals Inc	DILATRATE	isosorbide dinitrate	52244-920	ETHYLCELLULOSES
Endo Pharmaceuticals Inc	DILATRATE	isosorbide dinitrate	52244-920	GELATIN
Endo Pharmaceuticals Inc	DILATRATE	isosorbide dinitrate	52244-920	LACTOSE
Endo Pharmaceuticals Inc	DILATRATE	isosorbide dinitrate	52244-920	SUCROSE
Endo Pharmaceuticals Inc	DILATRATE	isosorbide dinitrate	52244-920	TALC

DILATRATE Excipient Strategy and Commercial Opportunities for Isosorbide Dinitrate Extended-Release Products

Last updated: August 15, 2026

DILATRATE, understood as Dilatrate-SR, is an extended-release isosorbide dinitrate product for angina prophylaxis and related cardiovascular use. Its commercial opportunity is primarily a low-cost generic, formulation-improvement, or niche 505(b)(2) strategy. The active ingredient has been marketed for decades, so value is more likely to come from release control, stability, packaging, supply reliability, and patient usability than from composition-of-matter exclusivity.

What is DILATRATE and which dosage form is commercially relevant?

Dilatrate-SR is an extended-release oral capsule containing isosorbide dinitrate. Isosorbide dinitrate is an organic nitrate that releases nitric oxide and produces vasodilation. The product is designed to reduce the frequency of angina attacks rather than treat an acute attack.

Attribute	Assessment
Brand	Dilatrate-SR
Active ingredient	Isosorbide dinitrate
Dosage form	Extended-release oral capsule
Therapeutic class	Organic nitrate; antianginal
Primary use	Prevention of angina pectoris
Regulatory category	Small-molecule prescription drug
Biosimilar pathway	Not applicable
Main competitive route	ANDA generic or 505(b)(2) reformulation
Principal formulation issue	Reproducible extended release with adequate dose uniformity
Principal commercial issue	Mature, price-sensitive market with limited brand loyalty

Immediate-release isosorbide dinitrate tablets and sublingual products compete with extended-release capsules. Isosorbide mononitrate, including extended-release products, is a related but distinct active ingredient and is a material commercial competitor.

What excipients are likely to be used in a Dilatrate-SR formulation?

The public label identifies the active ingredient and dosage form, but the complete qualitative and quantitative formulation is not necessarily disclosed in the prescribing information. A generic developer would therefore need to select excipients that reproduce the reference product’s release profile and physical performance rather than simply copy the nominal dosage form.[1]

A practical excipient platform would include the following categories:

Formulation function	Candidate excipient classes	Strategic purpose
Diluent or filler	Microcrystalline cellulose, lactose, mannitol, dibasic calcium phosphate	Controls capsule fill weight and blend uniformity
Release-controlling polymer	Hypromellose, ethylcellulose, methacrylate copolymers	Establishes sustained-release kinetics
Binder	Povidone, copovidone, hypromellose	Improves granule or pellet integrity
Glidant	Colloidal silicon dioxide	Improves flow and capsule filling
Lubricant	Magnesium stearate, sodium stearyl fumarate	Reduces manufacturing friction
Wetting or granulation aid	Purified water, hydroalcoholic process systems where justified	Supports granule formation
Capsule shell	Gelatin or hypromellose	Provides dose presentation and moisture protection
Colorant or opacifier	Titanium dioxide or approved color systems	Supports identification and light protection

The preferred platform depends on whether the product is manufactured as a powder-filled capsule, matrix granules, coated pellets, or multiparticulates.

Which excipient architecture is best for extended-release isosorbide dinitrate?

A multiparticulate or coated-pellet system offers the strongest technical control. Drug-loaded starter cores can be coated with ethylcellulose or a methacrylate polymer, then filled into hard capsules. This approach can reduce dose dumping risk and provide a more consistent release profile across manufacturing scale.

A hydrophilic matrix capsule is less complex and generally cheaper to manufacture. Hypromellose can create a gel barrier that slows drug diffusion. The principal risks are batch-to-batch variability, sensitivity to compression or granule density, and altered dissolution after changes in particle size or polymer viscosity.

A lipid or wax matrix can lower manufacturing complexity but may create more variable release in the presence of food, bile salts, or gastrointestinal motility differences. It is less attractive where bioequivalence depends on a narrow dissolution profile.

How should excipient selection address isosorbide dinitrate stability?

Isosorbide dinitrate is an organic nitrate ester. Moisture, heat, light, and reactive impurities are relevant development risks. Excipients should be selected through compatibility screening rather than by relying only on prior use in other oral products.

Key controls include:

1. Low-moisture excipient grades where feasible.
2. Control of residual peroxide in polymers and surfactants.
3. Avoidance of reactive amine-containing materials unless compatibility is demonstrated.
4. Low-temperature processing when granulation or coating permits.
5. Protection from excessive light exposure.
6. Tight control of water activity in the finished product.
7. Moisture-barrier packaging, preferably an aluminum-based blister or a high-barrier bottle system.
8. Stability-indicating assay and degradation-product methods.

Lactose, microcrystalline cellulose, mannitol, and hypromellose are commercially practical starting points, but each requires compatibility assessment against the selected drug load, process temperature, residual moisture, and packaging system. The lowest-cost excipient is not necessarily the lowest-cost formulation if it creates dissolution drift or stability failures.

What excipient strategy supports an ANDA for Dilatrate-SR?

An ANDA applicant must demonstrate pharmaceutical equivalence and bioequivalence to the reference listed drug. For an extended-release product, the dissolution method and profile are central development assets. The formulation must match the reference product’s release behavior across relevant pH conditions and, where required, under fed and fasting conditions.[2]

The development sequence should be:

1. Establish the reference product profile

The applicant should characterize:

• Capsule dimensions and fill characteristics.
• Drug content and content uniformity.
• Particle-size distribution.
• Dissolution across multiple media and sampling intervals.
• Fed-versus-fasted pharmacokinetics.
• Release behavior after alcohol exposure where relevant.
• Storage stability and package interaction.

2. Select a release platform

A hydrophilic matrix is likely to have the lowest capital requirement. Coated multiparticulates offer better control but require more process development, coating capacity, and in-process testing.

3. Minimize excipient complexity

A short excipient list reduces supply-chain risk and simplifies scale-up. Excessive use of polymers, surfactants, or pH modifiers can create regulatory questions and dissolution variability without adding commercial value.

4. Build a dissolution-based control strategy

The critical quality attributes should include drug release at early, middle, and terminal time points. The control strategy should also address capsule fill weight, polymer viscosity, coating weight gain, residual solvent, moisture, and assay uniformity.

5. Evaluate alcohol-induced dose dumping

Extended-release products require specific assessment of alcohol effects when the formulation could release drug more rapidly in alcoholic media. This is an important differentiation point for a robust generic product.

What is the Orange Book and patent status of DILATRATE?

Dilatrate-SR and isosorbide dinitrate are associated with an old small-molecule product class. The commercial opportunity is unlikely to depend on unexpired composition-of-matter protection. Any relevant protection would more likely involve an old extended-release formulation, manufacturing process, capsule system, or method of use.

Exclusivity issue	Commercial assessment
Composition-of-matter patent	Expected to be expired for this mature active ingredient
New-drug exclusivity	Expected to be expired
Orphan-drug exclusivity	Not generally associated with Dilatrate-SR
Biosimilar exclusivity	Not applicable
Current generic barrier	Formulation development, bioequivalence, and market economics
Paragraph IV exposure	Possible only if a relevant listed patent remains in the Orange Book
Method-of-use protection	Limited commercial relevance unless an active, listed claim covers the approved use
Formulation patent risk	Must be checked against current Orange Book listings and patent records

A generic applicant should not assume that the absence of an active ingredient patent eliminates all legal risk. The relevant questions are whether the reference product has active Orange Book-listed patents, whether those patents claim the dosage form or use, and whether any non-Orange-Book patents could support a separate litigation strategy.

A Paragraph IV certification could create an early-entry opportunity if an active listed patent remains and the applicant has a noninfringement, invalidity, or unenforceability position. If no relevant listed patent remains, a Paragraph III or “no patent” pathway may be more commercially efficient. FDA Orange Book records and the applicable reference product listing control the precise certification analysis.[3]

When does DILATRATE lose exclusivity?

Dilatrate-SR’s meaningful regulatory exclusivity is expected to have expired because isosorbide dinitrate products have been marketed for many years. The product should therefore be evaluated as a mature generic opportunity rather than as a protected branded asset.

The absence of exclusivity does not guarantee profitable entry. Extended-release products can remain commercially constrained by:

• Small prescription volume.
• Low reimbursement.
• Multiple established generic suppliers.
• Limited physician switching incentives.
• Manufacturing complexity relative to annual demand.
• Product discontinuation risk if price erosion exceeds production economics.

What commercial opportunities exist for DILATRATE excipients?

Low-cost generic extended-release capsule

The most direct opportunity is a standard ANDA using a simple hydrophilic matrix or controlled-release granule system. The commercial proposition would be reliable supply, competitive pricing, and consistent dissolution rather than clinical differentiation.

This model suits manufacturers with existing capsule-filling, granulation, and dissolution-testing infrastructure.

Premium generic with improved stability

A developer could use a high-barrier blister, low-moisture excipient system, and enhanced packaging to reduce degradation and extend shelf-life. The premium would be difficult to sustain in a commodity market but could support hospital, institutional, or wholesaler contracts where supply interruptions carry high costs.

505(b)(2) reformulation

A 505(b)(2) product could pursue a different dosage form, dosing interval, or delivery system. Potential concepts include:

• A more consistent once-daily extended-release capsule.
• A sprinkle-compatible capsule for patients with swallowing difficulty.
• A lower-pill-burden combination with another cardiovascular agent.
• A modified-release tablet or multiparticulate sachet.
• A formulation designed to reduce food-related pharmacokinetic variability.

The development burden would be materially higher than for an ANDA. The commercial case would require evidence of meaningful adherence, tolerability, administration, or pharmacokinetic benefit.

Excipient-led product differentiation

Excipient differentiation can support:

• Lower moisture sensitivity.
• Better capsule opening and sprinkle performance.
• Reduced capsule size.
• More consistent release across food conditions.
• Improved storage robustness.
• Use of globally available excipient grades.
• Reduced reliance on a single polymer supplier.

Excipient substitution alone generally does not create durable exclusivity. A defensible position requires a patentable formulation relationship, such as a defined polymer ratio, coating architecture, dissolution profile, stability outcome, or manufacturing process.

How does DILATRATE compare with isosorbide mononitrate products?

Isosorbide mononitrate is a direct commercial comparator because it is also used for angina prevention and has extended-release products. The two actives differ in pharmacology, dosing conventions, product history, and physician familiarity.

Factor	Isosorbide dinitrate, Dilatrate-SR	Isosorbide mononitrate ER
Active ingredient	Isosorbide dinitrate	Isosorbide mononitrate
Typical commercial positioning	Older extended-release nitrate	Established once-daily or modified-release nitrate
Generic maturity	High	High
Formulation opportunity	Release control and stability	Release control, adherence, and dosage convenience
Biosimilar relevance	None	None
Patent opportunity	Limited for legacy products	Limited for legacy products
Main commercial risk	Low volume and price erosion	Dense generic competition
Differentiation potential	Administration and supply reliability	Once-daily adherence and formulation convenience

A new DILATRATE product would need a clear reason to displace isosorbide mononitrate products. A lower price alone may be insufficient unless the manufacturer has a durable cost advantage.

Which manufacturing and intellectual-property barriers matter most?

The main barrier is process reproducibility. Extended-release performance can change with:

• Drug particle size.
• Excipient grade and viscosity.
• Granulation endpoint.
• Coating weight gain.
• Capsule fill density.
• Lubrication time.
• Residual moisture.
• Packaging permeability.

Potential patentable areas include a multiparticulate coating sequence, a specific polymer combination, an alcohol-resistant release profile, a low-moisture formulation, or a manufacturing process that produces consistent dissolution at commercial scale.

A patent strategy should focus on measurable product attributes and process controls. Broad claims covering isosorbide dinitrate with conventional fillers or lubricants are likely to face validity and prior-art challenges.

What generic launch scenarios exist?

Scenario 1: Standard ANDA launch

This is the lowest-risk commercial path if no active Orange Book patent blocks approval. The product enters a mature market with rapid price erosion and limited differentiation.

Scenario 2: Paragraph IV launch

If an active listed formulation or method patent exists, a Paragraph IV strategy could create a 180-day first-generic opportunity, subject to statutory requirements and litigation outcomes. The value depends on the size of the reference market and the number of other pending applicants.

Scenario 3: Authorized or licensed generic

A manufacturer could pursue a supply or licensing arrangement with the brand owner or an established generic company. This reduces launch risk but also limits margin and may not create meaningful exclusivity.

Scenario 4: 505(b)(2) reformulation

A reformulated product could command a higher price if it delivers a clinically relevant administration or adherence advantage. The development timeline, clinical requirements, and commercialization cost would exceed those of a conventional ANDA.

What is the revenue exposure and competitive outlook?

DILATRATE should be treated as a niche, mature cardiovascular product. Revenue potential depends on the specific strength, dosage form, market, channel, and number of approved suppliers. The commercial ceiling is likely lower than for high-volume antihypertensive or lipid-lowering generics.

The strongest business case is for a manufacturer that already has:

• A validated controlled-release platform.
• Existing U.S. capsule-filling capacity.
• Access to low-cost nitrate API.
• High-barrier packaging capability.
• A portfolio sales channel into hospitals or wholesalers.
• A strategy for maintaining supply during competitor exits.

The weakest case is a stand-alone investment in a new manufacturing platform dedicated only to Dilatrate-SR.

Key Takeaways

• Dilatrate-SR is an old isosorbide dinitrate extended-release product with limited expected regulatory exclusivity.
• The principal opportunity is a conventional ANDA, not a biosimilar or composition-of-matter strategy.
• Hydrophilic matrices offer lower development cost; multiparticulate coatings provide stronger release control.
• Moisture, light, heat, reactive impurities, and packaging permeability require early control.
• Excipient substitution is commercially useful but rarely creates durable exclusivity by itself.
• A 505(b)(2) product could support higher pricing only if it improves dosing convenience, administration, adherence, or pharmacokinetic consistency.
• The core commercial risks are low market volume, rapid generic price erosion, and the cost of maintaining a controlled-release manufacturing process.
• Patent value is likely concentrated in formulation architecture, process control, and stability performance rather than the active ingredient.
• Current Orange Book listings and patent certifications determine the precise Paragraph IV and launch analysis.

FAQs

Can DILATRATE be reformulated as a once-daily product?

Potentially, but a once-daily product would require new pharmacokinetic and clinical justification. It would more likely proceed under a 505(b)(2) pathway than as a straightforward ANDA if the dosing regimen differs from the reference product.

Which excipient is best for controlling isosorbide dinitrate release?

Hypromellose is a practical starting point for a hydrophilic matrix. Ethylcellulose or methacrylate polymers may provide tighter control in coated multiparticulate systems. The optimal choice depends on dissolution targets, food effects, moisture sensitivity, and manufacturing scale.

Is there a biosimilar opportunity for Dilatrate?

No. Isosorbide dinitrate is a chemically synthesized small molecule. Competition proceeds through generic-drug pathways rather than biosimilar approval.

Could a DILATRATE product use a sprinkle capsule?

A sprinkle capsule could provide a patient-use advantage, but the product would need to maintain dose uniformity, protect modified-release particles from crushing, and demonstrate bioequivalence or the applicable 505(b)(2) requirements.

Does an excipient patent provide meaningful protection for a DILATRATE generic?

It can if the claims cover a specific formulation architecture or process that competitors cannot readily design around. Conventional use of common fillers, binders, lubricants, or release polymers generally provides weak protection.

References

1. DailyMed. (n.d.). Dilatrate-SR: Isosorbide dinitrate capsule, extended release prescribing information. U.S. National Library of Medicine.

2. U.S. Food and Drug Administration. (2009). Bioequivalence recommendations for specific products: Isosorbide dinitrate extended-release oral dosage forms. Center for Drug Evaluation and Research.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. Center for Drug Evaluation and Research.

4. U.S. Food and Drug Administration. (2014). Guidance for industry: ANDAs for certain highly variable drugs. Center for Drug Evaluation and Research.

5. U.S. Pharmacopeial Convention. (2024). United States Pharmacopeia and National Formulary. USP Convention.