List of Excipients in Branded Drug LEVORPHANOL TARTRATE

Generic Drugs Containing LEVORPHANOL TARTRATE

Company	Ingredient	NDC	Excipient
Hikma Pharmaceuticals USA Inc	levorphanol tartrate	0054-0438	ANHYDROUS LACTOSE
Hikma Pharmaceuticals USA Inc	levorphanol tartrate	0054-0438	MAGNESIUM STEARATE
Hikma Pharmaceuticals USA Inc	levorphanol tartrate	0054-0438	STARCH, CORN
SpecGx LLC	levorphanol tartrate	0406-2224	ANHYDROUS LACTOSE
SpecGx LLC	levorphanol tartrate	0406-2224	MAGNESIUM STEARATE
SpecGx LLC	levorphanol tartrate	0406-2224	STARCH, CORN

What are the Most Frequently-Used Excipients in LEVORPHANOL TARTRATE?

# Of NDCs	Excipient
10	ANHYDROUS LACTOSE
1	CELLULOSE, MICROCRYSTALLINE
10	MAGNESIUM STEARATE
10	STARCH, CORN

Levorphanol Tartrate Excipient Strategy and Commercial Opportunities

Last updated: September 25, 2026

Levorphanol tartrate is an old, Schedule II opioid with limited current commercial supply and no meaningful remaining pioneer exclusivity. Its strongest commercial opportunities are niche products: reliable immediate-release tablets, low-volume hospital supply, patient-specific compounded dosage forms, and differentiated formulations that address dose flexibility, swallowing difficulty, or opioid abuse risk.

The principal barriers are regulatory control, small market size, limited prescriber familiarity, opioid liability, and the absence of a large reimbursement-driven market. Excipient selection should prioritize dose uniformity, chemical stability, tablet robustness, dissolution control, and manufacturing simplicity rather than expensive delivery technology.

What is levorphanol tartrate and how is it used?

Levorphanol tartrate is the tartrate salt of levorphanol, a potent opioid analgesic with activity at mu-opioid receptors and additional activity at NMDA and noradrenergic pathways. The FDA-approved product has historically been supplied as an immediate-release oral tablet, commonly at 2 mg strength. Levorphanol is used for severe pain when alternative treatments are inadequate, subject to opioid prescribing restrictions and boxed-warning requirements. [1]

Attribute	Levorphanol tartrate
Active ingredient	Levorphanol tartrate
Drug class	Opioid analgesic
U.S. controlled-substance status	Schedule II
Principal dosage form	Immediate-release oral tablet
Common historical strength	2 mg
Approved route	Oral
Primary commercial use	Severe pain requiring opioid therapy
Key safety issue	Respiratory depression, dependence, overdose, and drug interactions
FDA regulatory category	Small-molecule prescription drug
Biosimilar exposure	None

Levorphanol is not a biologic and therefore has no biosimilar pathway. Competitive pressure comes from generic opioids, specialty pain products, hospital suppliers, and compounded preparations.

What excipients are suitable for levorphanol tartrate tablets?

A conventional direct-compression or wet-granulated tablet is the lowest-risk platform. The formulation should control low-dose content uniformity because the active ingredient is potent and the usual tablet strength is small.

A practical excipient architecture includes:

Formulation function	Candidate excipients	Commercial rationale
Diluent	Lactose monohydrate, microcrystalline cellulose, dibasic calcium phosphate	Provides tablet mass and supports content uniformity
Binder	Povidone, pregelatinized starch, hydroxypropyl cellulose	Improves granule and tablet strength
Disintegrant	Crospovidone, croscarmellose sodium, sodium starch glycolate	Supports rapid immediate-release dissolution
Glidant	Colloidal silicon dioxide	Improves powder flow
Lubricant	Magnesium stearate, sodium stearyl fumarate	Supports compression and ejection
Anti-adherent	Talc, where justified	Reduces sticking during compression
Film coating	Hypromellose, polyethylene glycol, titanium dioxide, iron oxides	Improves handling, identification, and light protection
Sweetener or flavor	Sucralose, mannitol, selected flavors	Relevant to orally disintegrating or chewable products

Historical U.S. levorphanol tablet labels have used conventional pharmaceutical excipients, including lactose, starch-based materials, and magnesium stearate. Exact inactive ingredients should be confirmed against the target reference product and the proposed regulatory filing because supplier, strength, and manufacturing site can change the excipient profile. [1]

Which excipients best support a 2 mg immediate-release tablet?

Microcrystalline cellulose combined with lactose or dibasic calcium phosphate is a practical starting system. Crospovidone or croscarmellose sodium can provide rapid disintegration without requiring an aggressive formulation.

The main technical risks are:

1. Content uniformity. Low-dose opioid products require controlled blending, ordered mixing, or granulation to prevent active segregation.
2. Over-lubrication. Excess magnesium stearate can slow dissolution and reduce tablet strength.
3. Dissolution variability. Changes in particle size, granule density, or disintegrant level can materially alter release.
4. Stability. Packaging must control moisture and protect tablets from mechanical abrasion.
5. Manufacturing containment. Facilities must manage potent active handling, cleaning validation, and Schedule II inventory controls.

A wet-granulation process may improve content uniformity and flow where direct compression produces segregation. Direct compression remains attractive for a low-volume product because it reduces process steps and development cost.

What formulation patents protect levorphanol tartrate?

Levorphanol tartrate is an old active pharmaceutical ingredient. The original composition-of-matter and basic oral formulation protection would have expired decades ago. No credible commercial strategy should depend on exclusivity for the conventional 2 mg immediate-release tablet.

Potentially protectable subject matter may include:

• An orally disintegrating tablet with defined disintegration and dissolution limits.
• A taste-masked liquid or orally disintegrating formulation.
• A controlled-release formulation with a specific pharmacokinetic profile.
• A tamper-resistant or abuse-deterrent dosage form.
• A manufacturing process that improves content uniformity or impurity control.
• A combination product with a defined clinical or pharmacokinetic advantage.
• A novel salt, polymorph, co-crystal, or particle-engineered form, if patentable and clinically relevant.

These categories would require new development work and cannot be treated as existing rights. A formulation patent would also need to withstand obviousness challenges because conventional excipient combinations and immediate-release opioid technologies are heavily developed.

When does levorphanol tartrate lose exclusivity?

The relevant loss-of-exclusivity event occurred long ago. Levorphanol has no meaningful remaining new-drug exclusivity period for its conventional oral tablet. FDA approval of a current generic product does not create a new period of market exclusivity merely because the product is manufactured by a different company. [2]

Exclusivity category	Commercial status
Original composition-of-matter patent	Expired
Conventional tablet formulation patents	Expired or commercially immaterial
New chemical entity exclusivity	Expired
Orphan-drug exclusivity	Not applicable to the conventional product
Pediatric exclusivity	No current commercial relevance identified
Biosimilar exclusivity	Not applicable
Generic competition	Legally available, subject to product availability and ANDA status

What is the Orange Book status of levorphanol tartrate?

Levorphanol tartrate has historically been listed in FDA-approved prescription drug references as an oral tablet product. Orange Book status can change as approvals are withdrawn, products are discontinued, or manufacturers update marketing status. [2]

The commercial significance is straightforward:

• Any active approved ANDA may support lawful generic competition.
• A product marked discontinued may still have an approved application but no active commercial supply.
• A shortage or intermittent supply position can create an opportunity even without patent protection.
• Orange Book patent listings are unlikely to create a meaningful barrier for the conventional tablet because the product is old and genericized.

The key distinction is between approved, marketed, and reliably available. A company can face limited competition even where several approvals exist if few manufacturers maintain active commercial inventory.

What Paragraph IV challenges affect levorphanol tartrate?

Paragraph IV litigation is unlikely to be the central issue for the conventional levorphanol tartrate tablet. Paragraph IV certifications are most commercially relevant when an ANDA applicant challenges unexpired patents listed for an approved reference product. [3]

For levorphanol:

• A conventional generic entrant would generally face an old, mature product category.
• The main commercial risk is manufacturing and regulatory execution, not pioneer patent litigation.
• A Paragraph IV strategy could become relevant only if a newer formulation, abuse-deterrent product, or other protected reference product receives valid listed patents.
• A newly patented delivery system would likely generate a different litigation profile from the legacy 2 mg tablet.

No current broad patent barrier should be assumed for the standard immediate-release dosage form.

What formulation opportunities exist for levorphanol tartrate?

Orally disintegrating tablets

An orally disintegrating tablet could address patients with dysphagia and improve administration in palliative-care settings. Mannitol, microcrystalline cellulose, crospovidone, and a taste-masking system are technically plausible excipient choices.

The principal risks are bitter taste, dose uniformity, friability, moisture sensitivity, and the possibility that a rapid-dissolving opioid product could create abuse or diversion concerns. Any ODT would need strong packaging and clear pharmacokinetic comparability data.

Oral liquid

A concentrated oral solution could support individualized dosing and hospice use. Formulation development would need to address:

• Solubility of levorphanol tartrate across the target pH range.
• Preservative effectiveness.
• Chemical and microbiological stability.
• Dose-measuring-device accuracy.
• Child-resistant packaging.
• Accidental ingestion and diversion risk.

A unit-dose oral liquid may have stronger institutional utility than a multidose bottle because it reduces measurement errors and inventory exposure.

Modified-release tablets

Modified release could reduce dosing frequency, but the opportunity is technically and commercially difficult. Levorphanol has potent opioid activity, and dose dumping or manipulation could produce severe toxicity. A modified-release product would require robust abuse-risk analysis and pharmacokinetic bridging.

Potential excipients include hydrophilic matrix polymers such as hypromellose, hydrophobic release modifiers, and barrier coatings. A controlled-release product would likely need a clinically meaningful advantage to justify development costs.

Abuse-deterrent formulation

Abuse-deterrent technology could use polymer matrices, gelling systems, physical barriers, or difficult-to-crush tablet structures. FDA guidance evaluates whether a product meaningfully impedes common manipulation routes such as crushing, grinding, chewing, or extraction. Abuse-deterrent labeling does not eliminate overdose, addiction, or diversion risk. [4]

The commercial case is weak unless a sponsor can secure differentiated labeling, institutional adoption, or a contract with a large buyer. A high-cost abuse-deterrent product would compete against inexpensive generic opioids.

Compounded dosage forms

Compounding pharmacies may have demand for nonstandard strengths, capsules, suspensions, or patient-specific preparations when commercial supply is limited. This is a service opportunity rather than a conventional branded-drug opportunity.

Compounded products must comply with applicable federal and state requirements. They cannot be treated as a substitute for FDA approval, and a manufacturer should not rely on compounding demand as evidence of broad commercial potential. [5]

How does levorphanol compare with competing opioids?

Product	Main advantage	Main commercial disadvantage	Excipient opportunity
Levorphanol tartrate	Potent analgesia and distinctive pharmacology	Low prescriber familiarity and limited supply	Reliable low-dose tablet, ODT, liquid
Morphine sulfate	Broad clinical familiarity and multiple dosage forms	Extensive generic competition and opioid safety burden	Low-cost hospital and palliative-care products
Methadone hydrochloride	Low cost and multiple clinical uses	Complex pharmacokinetics and QT-prolongation concerns	Abuse-resistant liquid and dose-control systems
Oxycodone	Large historical prescribing base	High competition and severe abuse scrutiny	Mostly commodity generic opportunity
Buprenorphine	Established opioid-use-disorder market	Different clinical positioning and regulatory competition	Sublingual films, tablets, and long-acting systems
Hydromorphone	High potency and hospital use	Narrower market and safety concerns	Injectable and hospital-focused dosage forms

Levorphanol’s differentiation is pharmacological rather than brand-driven. Its commercial value is highest where clinicians specifically prefer its profile or where alternative opioid products are unavailable.

Which companies are challenging or supplying levorphanol tartrate?

The market is likely to include generic drug manufacturers, contract manufacturers, specialty distributors, and compounding pharmacies rather than a dominant innovator. Company participation can vary because opioid products require Schedule II quotas, controlled-substance registrations, specialized distribution controls, and inventory commitments.

The most credible supply models are:

1. A generic manufacturer with an existing controlled-substance portfolio.
2. A specialty pharmaceutical company serving palliative care or pain clinics.
3. A contract development and manufacturing organization with Schedule II capabilities.
4. A hospital-focused supplier seeking a low-volume, high-reliability product.
5. A licensing company acquiring an approved but inactive application and reactivating supply.

Public revenue data for levorphanol alone is generally unavailable. A sponsor should model the opportunity using prescription volume, average selling price, discontinuation rates, wholesaler inventory, and institutional demand rather than relying on broad opioid market figures.

What generic launch risks exist for levorphanol tartrate?

The principal risks are operational and regulatory:

• Schedule II quota limitations.
• API availability and qualified-source requirements.
• Low annual volume and unfavorable manufacturing economics.
• FDA inspection findings.
• Product withdrawal or temporary supply interruptions.
• Opioid REMS and controlled-substance compliance.
• Diversion, theft, and suspicious-order monitoring.
• Low prescriber awareness.
• Payer preference for more familiar generic opioids.
• Product liability exposure.
• Difficulty obtaining reliable commercial forecasts.

A launch can be attractive if competitors have discontinued products, stock-outs, or poor customer service. The opportunity is less attractive if multiple suppliers maintain stable inventory at low generic prices.

What FDA regulatory requirements apply to levorphanol formulations?

A new conventional tablet would generally be pursued through an abbreviated new drug application if a suitable reference product and regulatory pathway are available. The sponsor would need to address pharmaceutical equivalence, bioequivalence, active-ingredient sourcing, manufacturing controls, labeling, and controlled-substance compliance. [2,3]

A novel dosage form may require a more extensive development package, including:

• Comparative pharmacokinetics.
• Food-effect assessment where relevant.
• Dose proportionality.
• In vitro dissolution and abuse-manipulation studies.
• Stability and extractables or leachables data for liquid products.
• Human-factors work for dose-measuring devices.
• Clinical justification for modified-release or abuse-deterrent claims.

FDA opioid labeling includes boxed warnings addressing addiction, abuse, misuse, life-threatening respiratory depression, accidental ingestion, neonatal opioid withdrawal, and risks from benzodiazepines or other central nervous system depressants. [1,6]

How strong is the levorphanol tartrate patent estate?

The legacy patent estate is weak for the standard immediate-release tablet. The absence of meaningful remaining exclusivity creates low entry barriers from a patent perspective, but it does not make the market easy to enter.

Patent-estate factor	Assessment
Active ingredient	Mature and historically genericized
Conventional 2 mg tablet	Weak patent differentiation
New dosage forms	Potentially patentable
Abuse-deterrent technology	Potentially patentable, but obviousness risk is high
Manufacturing process	Possible trade-secret and process-patent value
Regulatory exclusivity	No current meaningful exclusivity expected for the legacy product
Litigation exposure	More likely for a new formulation than for the standard tablet

Manufacturing know-how may provide more practical protection than patents. Examples include blend-order control, low-dose content-uniformity methods, impurity management, cleaning validation, and robust packaging.

What licensing deals and commercial structures are viable?

The most viable transaction structures are:

• Acquisition or licensing of an approved but inactive generic application.
• Exclusive supply agreement with a controlled-substance API manufacturer.
• Co-development of an ODT or oral liquid.
• Hospital or hospice supply contracts.
• Regional distribution rights.
• CDMO-led development with milestone payments and supply margins.
• Licensing of an abuse-deterrent platform applied to levorphanol.

A conventional tablet is unlikely to support large upfront payments. Deal value would depend on reliable supply, regulatory status, manufacturing capacity, and access to institutional customers.

Key Takeaways

• Levorphanol tartrate is a mature Schedule II opioid with no meaningful remaining pioneer exclusivity for the conventional tablet.
• The strongest formulation platform is a simple immediate-release tablet using standard diluents, binders, disintegrants, glidants, and lubricants.
• Content uniformity, dissolution, stability, controlled-substance compliance, and supply reliability are the central development issues.
• ODT, oral liquid, modified-release, and abuse-deterrent products offer potential differentiation but require substantially higher development investment.
• The commercial opportunity is niche and supply-driven, not a broad mass-market generic opportunity.
• Patent value is more likely to arise from a genuinely differentiated dosage form or manufacturing process than from the active ingredient.
• The most credible business models are generic relaunch, specialty distribution, hospital supply, CDMO development, and patient-specific dosage-form support.

FAQs

Is levorphanol tartrate still commercially available in the United States?

Availability has been intermittent and supplier-dependent. An approved product may not be consistently marketed or stocked, creating a potential supply opportunity for a manufacturer with controlled-substance capabilities.

Can levorphanol tartrate be developed as an abuse-deterrent opioid?

Yes. A sponsor could pursue physical, chemical, or pharmacokinetic abuse-deterrent properties. The product would need evidence under FDA abuse-deterrent guidance and would still carry opioid addiction and overdose warnings.

Which excipient is best for a levorphanol tartrate tablet?

No single excipient is universally preferred. A combination of microcrystalline cellulose or lactose with crospovidone or croscarmellose sodium and a low level of magnesium stearate is a practical starting point for an immediate-release tablet.

Is an orally disintegrating levorphanol product commercially attractive?

It may be attractive in hospice, palliative care, and dysphagia populations. The opportunity is limited by the small market, taste-masking requirements, opioid diversion concerns, and the need to demonstrate reliable dose delivery.

Does levorphanol tartrate have biosimilar competition?

No. Levorphanol tartrate is a small-molecule drug. Competition comes from generic opioids and alternative opioid formulations, not biosimilars.

References

1. U.S. Food and Drug Administration. (2023). Levorphanol tartrate tablets prescribing information. DailyMed.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugsatfda

3. U.S. Food and Drug Administration. (2019). Approved drug products with therapeutic equivalence evaluations: 39th edition. U.S. Department of Health and Human Services.

4. U.S. Food and Drug Administration. (2015). Guidance for industry: Abuse-deterrent opioids: Evaluation and labeling. U.S. Department of Health and Human Services.

5. U.S. Food and Drug Administration. (2023). Compounding and the FDA: Questions and answers. U.S. Department of Health and Human Services.

6. U.S. Food and Drug Administration. (2020). Opioid analgesic drugs: Drug safety communication and labeling requirements. U.S. Department of Health and Human Services.