List of Excipients in Branded Drug DHIVY

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Avion Pharmaceuticals LLC	DHIVY	carbidopa levodopa	75854-701	CELLULOSE, MICROCRYSTALLINE
Avion Pharmaceuticals LLC	DHIVY	carbidopa levodopa	75854-701	MAGNESIUM STEARATE
Avion Pharmaceuticals LLC	DHIVY	carbidopa levodopa	75854-701	STARCH, CORN

DHIVY Excipient Strategy and Commercial Opportunities

Last updated: August 6, 2026

DHIVY is an immediate-release, four-way scored carbidopa/levodopa tablet developed to provide smaller dose increments for Parkinson's disease treatment. Its commercial differentiation depends less on the active ingredients than on tablet architecture, splitting performance, content uniformity, and dose flexibility. The strongest excipient opportunities are in low-friability direct-compression systems, co-processed fillers, disintegrants, lubricants, and alternative dosage forms that preserve dose accuracy after tablet subdivision.

DHIVY contains 25 mg of carbidopa and 100 mg of levodopa per tablet. The tablet can be divided into halves and quarters, allowing doses as small as 6.25 mg of carbidopa and 25 mg of levodopa when prescribed according to the product labeling. Avion Pharmaceuticals markets DHIVY in the United States under NDA 214165. The FDA approved the product in November 2021.[1]

What is DHIVY and why does its excipient system matter?

DHIVY is a scored immediate-release tablet for Parkinson's disease and parkinsonism. Its value proposition is dose titration, not a new active pharmaceutical ingredient.

Levodopa has a narrow practical dosing window for many patients. Clinicians often adjust therapy to balance motor benefit against dyskinesia, nausea, hallucinations, and other adverse effects. A tablet that can be divided into consistent fractions gives prescribers more dose increments than an unsplit 25/100-mg product.

That design creates formulation requirements that are more demanding than those for a conventional unscored tablet:

• The tablet must break along intended score lines.
• Quarter segments should retain acceptable mass and drug-content uniformity.
• Splitting should not produce excessive powder or edge chipping.
• Disintegration and dissolution should remain consistent after subdivision.
• The tablet must withstand packaging, shipping, and patient handling.
• Lubrication must support manufacturability without slowing dissolution.
• The formulation must remain stable because levodopa is oxidation-sensitive.

An excipient that performs well in a standard tablet may not perform well in a four-way scored tablet. The formulation must balance mechanical strength with controlled breakability.

What excipients are used in DHIVY?

The FDA prescribing information identifies DHIVY as a tablet containing carbidopa and levodopa with inactive ingredients that support compression, flow, lubrication, and disintegration.[1] Public product information identifies excipient classes including microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate, and related tablet-processing components. The precise commercial composition should be confirmed against the current FDA labeling and DailyMed record before a regulatory or sourcing decision.[1,2]

Likely functional roles of the DHIVY excipients

Excipient class	Primary function	Relevance to DHIVY
Microcrystalline cellulose	Filler, dry binder, compressibility aid	Supports tablet strength and direct compression
Crospovidone or equivalent superdisintegrant	Rapid water uptake and tablet breakup	Helps maintain immediate-release performance
Colloidal silicon dioxide	Glidant, flow aid, moisture-management aid	Supports uniform die filling at low tablet weight
Magnesium stearate	Lubricant	Reduces ejection force but can retard wetting if overused
Binder or polymeric processing aid	Particle adhesion and strength	May improve resistance to chipping and handling damage

The key formulation issue is the interaction between filler level, compression force, lubricant concentration, and score geometry. Higher compression can improve handling strength but make quartering difficult. Higher disintegrant levels can improve breakup but reduce tensile strength or increase friability. Excessive magnesium stearate can create hydrophobic surfaces and delay dissolution.

How should an excipient strategy optimize DHIVY manufacturing?

The most commercially attractive strategy is a direct-compression platform engineered around dose uniformity and score-line performance.

1. Use a co-processed filler system

A co-processed microcrystalline cellulose and mannitol, lactose, or similar system could improve flow and compactability while reducing formulation sensitivity. The objective is not simply to increase hardness. It is to produce a tablet with:

• Consistent die fill
• Low weight variation
• Adequate tensile strength
• Controlled friability
• Predictable quarter splitting
• Rapid disintegration

Co-processed excipients can reduce the number of separate raw materials and simplify scale-up. They can also provide a more consistent particle-size distribution than a formula assembled from multiple conventional grades.

2. Control lubricant sensitivity

Magnesium stearate is effective but can impair wetting and dissolution when over-lubrication occurs. DHIVY manufacturers should evaluate:

• Lubrication time
• Lubricant concentration
• Blend order
• Shear exposure
• Granule or powder surface area
• Dissolution after tablet splitting

Alternative lubricants, including sodium stearyl fumarate or specialized low-hydrophobicity systems, may create opportunities where dissolution margins are narrow. Any substitution would require comparative dissolution, stability, impurity, and tablet-performance data.

3. Protect levodopa from oxidation

Levodopa can undergo oxidative degradation under unfavorable moisture, oxygen, light, pH, or trace-metal conditions. Excipient selection should therefore address:

• Peroxide values in polymeric excipients
• Residual moisture
• Trace metals
• Oxygen exposure
• Packaging compatibility
• Long-term impurity growth

Low-peroxide grades of povidone, crospovidone, and other polymers may provide a commercial advantage. The formulation may also benefit from improved moisture-barrier packaging, desiccant integration, or oxygen-control measures. These changes are manufacturing and stability opportunities even when the tablet's active ingredients remain unchanged.

4. Engineer for quarter-dose integrity

The central technical challenge is not tablet hardness alone. It is whether each quarter contains an acceptable fraction of the labeled dose after routine patient splitting.

Development programs should measure:

• Mass of whole, half, and quarter tablets
• Carbidopa and levodopa content in each fraction
• Friability before and after splitting
• Powder loss
• Dissolution profiles for intact and split pieces
• Breaking force
• Score-line alignment
• Storage effects on splitting behavior

A formulation platform that improves dose uniformity after quartering could support differentiated supply agreements with generic manufacturers, CDMOs, or specialty-pharmacy companies.

What formulation patents may protect DHIVY?

DHIVY's defensible value is likely concentrated in dosage-form and manufacturing claims rather than API composition claims. Carbidopa and levodopa have long-established clinical and chemical histories, limiting the value of composition-of-matter protection.

Potential claim areas include:

• Four-way scored tablet geometry
• Dose uniformity after subdivision
• Specific carbidopa-to-levodopa ratios
• Immediate-release dissolution performance
• Excipient concentration ranges
• Compression and manufacturing parameters
• Reduced tablet-fraction variability
• Stability and impurity control
• Use of the tablet for fine-dose titration

The FDA Orange Book should be reviewed for patents listed against NDA 214165, while the USPTO Patent Center and Google Patents can be used to trace continuations, terminal disclaimers, assignments, and expiration calculations.[3,4] Patent strength will depend on whether claims cover the commercial product broadly or rely on narrow excipient ranges and process conditions.

How strong is the DHIVY patent estate?

The estate is likely stronger against a technically identical four-way scored product than against all carbidopa/levodopa tablets. A generic applicant could attempt to design around:

• Score depth
• Tablet shape
• Excipient identity
• Compression profile
• Release characteristics
• Packaging configuration

A narrow formulation patent may still create regulatory and litigation value if it covers the only commercially practical way to achieve consistent quarter doses. A broad method-of-use patent for Parkinson's disease dosing would face greater validity and enforceability pressure because carbidopa/levodopa titration is well established.

When does DHIVY lose exclusivity?

DHIVY does not receive new chemical entity exclusivity because carbidopa and levodopa are established active ingredients. FDA exclusivity may arise from the approved NDA's clinical-investigation or other regulatory designation, but the commercial timing is primarily patent-driven.[3]

Key exclusivity questions include:

Issue	Commercial impact
NDA approval date	November 2021
NCE exclusivity	Not applicable
Three-year clinical-investigation exclusivity	Depends on the FDA-designated regulatory basis
Listed patents	Must be confirmed in the current Orange Book
Paragraph IV filings	Could trigger litigation and a 30-month stay
Patent expiry	Depends on the listed patent family and PTA/PTE calculations
Generic substitution	Depends on ANDA approval, labeling, scoring, and pharmacy substitution rules

A Paragraph IV ANDA certification could create litigation under the Hatch-Waxman Act. If the NDA holder sues within the statutory period, FDA approval may be stayed for up to 30 months, subject to court action and statutory exceptions.[5]

What generic entry risks exist for DHIVY?

Generic entry risk is meaningful because the underlying API combination is mature and widely manufactured. The main barrier is reproducing the product's subdivision performance, not sourcing carbidopa or levodopa.

High-risk generic scenarios

A generic applicant could pursue an ANDA for:

1. A substantially identical four-way scored 25/100-mg tablet.
2. A product with the same active ingredients but different excipients.
3. A different score configuration that provides equivalent dosing.
4. A conventional unscored carbidopa/levodopa tablet that competes on price but does not replicate DHIVY's dose flexibility.

The first scenario creates the greatest patent and formulation risk. The fourth may be easier from a regulatory standpoint but would compete less directly for patients who need quarter-tablet titration.

FDA approval of a generic does not automatically establish that the generic will match DHIVY's practical splitting characteristics. Product-specific handling, patient instructions, and physician preference can preserve some branded demand after generic entry.

What regulatory pathway applies to DHIVY and future alternatives?

A directly substitutable generic would generally use the ANDA pathway and must demonstrate pharmaceutical equivalence and bioequivalence to the reference listed drug.[6] A reformulated product with a new dosage form, new delivery system, or materially different clinical use could require a 505(b)(2) application.

Potential 505(b)(2) opportunities include:

• Orally disintegrating carbidopa/levodopa
• Liquid or reconstitutable formulations
• Sprinkle capsules
• Chewable tablets
• Modified-release products with smaller titration increments
• Gastroretentive or other targeted delivery systems
• Combination products that reduce pill burden

The clinical and commercial value of these products would depend on whether they solve a specific limitation of DHIVY, such as swallowing difficulty, dysphagia, dose timing, overnight symptoms, or adherence.

What commercial opportunities exist for excipient suppliers?

The opportunity extends beyond supplying commodity excipients.

High-value opportunities

Co-processed direct-compression platforms

Suppliers can offer validated systems optimized for low-dose, scored tablets. Performance data should focus on splitting uniformity, not only tablet hardness and dissolution.

Low-peroxide excipient grades

Excipient suppliers can differentiate through peroxide control, trace-metal specifications, and stability data relevant to levodopa.

Functional lubricant systems

Low-hydrophobicity lubricants and optimized lubrication packages could improve dissolution robustness while maintaining tablet ejection performance.

CDMO formulation packages

A CDMO could offer a complete platform covering powder characterization, tooling, compression, score design, split testing, packaging, and stability. This would reduce development risk for companies seeking a DHIVY-compatible generic or follow-on product.

Alternative dosage forms

Excipient suppliers with orally disintegrating, taste-masking, or liquid-dispersion technologies could target next-generation carbidopa/levodopa products. Taste masking is especially relevant to liquid or orally disintegrating systems because levodopa formulations can create palatability challenges.

How does DHIVY compare with conventional carbidopa/levodopa products?

Attribute	DHIVY	Conventional immediate-release tablets
Active ingredients	Carbidopa and levodopa	Carbidopa and levodopa
Core differentiation	Four-way scoring and dose flexibility	Standard tablet dosing
API barrier	Low	Low
Formulation barrier	Moderate to high	Low to moderate
Excipient opportunity	High	Moderate
Generic design-around risk	Moderate	High
Patient value	Fine titration	Established low-cost therapy
Main commercial defense	Dose precision and usability	Price, supply, and prescriber familiarity

DHIVY's commercial exposure is concentrated in patients and prescribers who value small dose adjustments. Revenue durability will depend on whether that segment accepts a premium over conventional tablets and whether generic competitors can reproduce quarter-dose performance.

What is the commercial outlook for DHIVY?

DHIVY is a formulation-led specialty product in a mature API market. Its commercial upside depends on three factors:

1. Sustained physician recognition of dose-splitting advantages.
2. Reimbursement sufficient to support a premium product.
3. Patent and formulation barriers that delay a close generic substitute.

The product has limited biosimilar risk because it is a small-molecule tablet, not a biologic. Its principal threats are ANDA-based generic entry, therapeutic substitution with conventional carbidopa/levodopa, and alternative formulations that offer similar dosing flexibility.

For investors and licensing teams, the most attractive assets are likely to be the tablet technology, score-line engineering, stability package, and any validated manufacturing process that improves fraction-dose uniformity. Commodity excipient supply alone is less defensible unless linked to performance data or a proprietary co-processed platform.

Key Takeaways

• DHIVY's differentiation is its four-way scored carbidopa/levodopa tablet, not a novel API.
• The most important excipient attributes are compressibility, low friability, rapid disintegration, low peroxide burden, and compatibility with quarter-tablet dosing.
• Microcrystalline cellulose, superdisintegrants, colloidal silicon dioxide, and magnesium stearate are central formulation categories.
• Co-processed fillers and low-peroxide excipient grades offer the clearest commercial opportunities.
• Generic risk is substantial because the APIs are old, but reproducing reliable quarter-dose performance is more difficult than reproducing the API combination.
• Patent value is likely concentrated in scored-tablet design, dose-fraction uniformity, formulation ranges, and manufacturing methods.
• DHIVY has no biosimilar risk. Its main threats are ANDA entry, therapeutic substitution, and competing flexible-dose formulations.
• The strongest licensing targets are formulation platforms, score-line technology, stability-control systems, and CDMO packages.

FAQs

Can a generic manufacturer use different excipients from DHIVY?

Yes. An ANDA applicant generally may use different inactive ingredients if the product meets applicable equivalence, safety, quality, dissolution, and labeling requirements. Different excipients may affect splitting, stability, and release performance.

Why is quarter-tablet uniformity commercially important for DHIVY?

Quartering is the product's main clinical-use advantage. Poor fraction uniformity would reduce dose precision and weaken the distinction between DHIVY and conventional carbidopa/levodopa tablets.

Are excipient patents likely to block DHIVY generic entry?

They can, but blocking power depends on claim breadth, validity, infringement, and whether a generic can design around the claimed excipient ranges or manufacturing steps. A narrow excipient claim may have less practical value than a broad claim covering the scored tablet and its dose-fraction performance.

Could an orally disintegrating DHIVY alternative use the 505(b)(2) pathway?

Potentially. A materially different dosage form or delivery system could rely on FDA findings for the existing product while submitting new clinical, quality, or bioavailability data under section 505(b)(2).

What is the largest unmet formulation opportunity for carbidopa/levodopa?

Flexible delivery for patients with dysphagia, variable gastric emptying, or difficult dose titration is the clearest opportunity. Liquid, orally disintegrating, sprinkle, and other patient-administered formats could compete with DHIVY if they preserve dose accuracy and improve usability.

References

1. U.S. Food and Drug Administration. (2021). DHIVY (carbidopa and levodopa) tablets, prescribing information.
2. National Library of Medicine. (n.d.). DailyMed: DHIVY, carbidopa and levodopa tablet.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
4. United States Patent and Trademark Office. (n.d.). Patent Center.
5. U.S. Food and Drug Administration. (2017). ANDA submissions: Amendments and requests for final approval to tentatively approved ANDAs.
6. U.S. Food and Drug Administration. (2024). Guidance for industry: Bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA.