List of Excipients in Branded Drug BUTORPHANOL TARTRATE

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Generic Drugs Containing BUTORPHANOL TARTRATE

Company	Ingredient	NDC	Excipient
Hikma Pharmaceuticals USA Inc	butorphanol tartrate	0054-3090	ANHYDROUS CITRIC ACID
Hikma Pharmaceuticals USA Inc	butorphanol tartrate	0054-3090	BENZETHONIUM CHLORIDE
Hikma Pharmaceuticals USA Inc	butorphanol tartrate	0054-3090	HYDROCHLORIC ACID
Hikma Pharmaceuticals USA Inc	butorphanol tartrate	0054-3090	SODIUM CHLORIDE

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

# Of NDCs	Excipient
2	ANHYDROUS CITRIC ACID
5	BENZETHONIUM CHLORIDE
4	CITRIC ACID MONOHYDRATE
4	HYDROCHLORIC ACID

Butorphanol Tartrate Excipient Strategy and Commercial Opportunities

Last updated: August 17, 2026

Butorphanol tartrate is an established opioid analgesic with limited remaining exclusivity value and a larger opportunity in differentiated delivery systems. The strongest commercial prospects are preservative-free injectable products, improved intranasal formulations, veterinary dosage forms, and controlled-delivery products that address handling, tolerability, abuse risk, or administration efficiency.

Human products are primarily constrained by opioid regulation, generic price competition, and the need for clinical evidence when a new route, device, or dosing profile is introduced. Excipient innovation can support a 505(b)(2) strategy, but an excipient change alone is unlikely to create durable protection unless it produces a clinically meaningful formulation or delivery advantage.

What is butorphanol tartrate and how is it used?

Butorphanol tartrate is the tartrate salt of butorphanol, a synthetic opioid with agonist and antagonist activity at opioid receptors. Human indications have included short-term management of pain and migraine, depending on the dosage form and applicable labeling. Veterinary products are used for analgesia, sedation, and preanesthetic purposes in several species.

Attribute	Butorphanol tartrate
Drug class	Opioid analgesic; mixed agonist-antagonist
Common human routes	Intramuscular, intravenous, intranasal
Common veterinary routes	Injectable; species-specific formulations
Human regulatory category	Controlled opioid; U.S. Schedule IV
Key formulation issue	Aqueous stability, pH control, preservative strategy, dosing accuracy
Main commercial constraint	Mature generic market and opioid-related regulatory controls
Biosimilar exposure	None; butorphanol is a small molecule
Primary development paths	Generic injectable, 505(b)(2) intranasal or transmucosal product, veterinary reformulation

Butorphanol tartrate is water soluble enough for aqueous injectable and nasal products. Formulation development therefore focuses less on overcoming extreme solubility limitations and more on chemical stability, tolerability, microbiological control, device performance, and dose delivery.

What excipients are used in butorphanol tartrate products?

Approved product labels identify excipients that have included sodium chloride, citrate buffers, water for injection, and preservatives in multidose presentations. Exact composition varies by manufacturer, route, strength, container, and market.

Injectable formulation excipients

Human butorphanol tartrate injection products generally use a simple aqueous system. The formulation objectives are:

• Maintain drug solubility across the labeled temperature range.
• Control pH and reduce degradation.
• Match osmolality for parenteral administration.
• Limit particulate formation and container interaction.
• Support either single-dose or multidose packaging.

Sodium chloride can provide isotonicity. Citric acid and sodium citrate can establish buffer capacity and pH control. Water for injection is the primary vehicle. A multidose product may require a preservative, while a single-dose presentation can avoid preservative exposure.

A preservative-free product could have commercial value in patients exposed to repeated injections, in hospitals seeking simplified medication protocols, or where preservative avoidance is clinically preferred. The commercial case depends on whether the manufacturer can demonstrate a meaningful safety, handling, or procurement benefit over low-cost generic vials.

Intranasal formulation excipients

Butorphanol nasal spray requires tighter control of several variables:

• Delivered dose per actuation.
• Droplet or plume characteristics.
• Nasal retention and mucosal clearance.
• Local irritation.
• Microbial control in a multidose container.
• Stability after repeated priming and use.
• Device compatibility.

Historical nasal products have used aqueous systems containing sodium chloride, buffering agents, and a preservative such as benzethonium chloride. A future product could examine preservative-free multidose technology, unit-dose packaging, or a different preservative system. Any change must be assessed for local tolerability, microbial robustness, extractables and leachables, and dose uniformity.

Mucoadhesive excipients, including selected cellulose derivatives, polyacrylic acid systems, or thermoresponsive polymers, could increase residence time. Their use creates formulation risks: slower onset, altered absorption, nasal obstruction, local irritation, and greater batch-to-batch variability. A mucoadhesive strategy is commercially credible only if it improves exposure or reduces dosing frequency without impairing the rapid onset expected from intranasal delivery.

What is the best excipient strategy for butorphanol tartrate?

The most practical strategy is route-specific rather than based on a single novel excipient.

Product concept	Excipient strategy	Commercial rationale	Main development risk
Preservative-free injection	Buffered isotonic aqueous solution in single-dose container	Reduces preservative exposure and may simplify hospital use	Low price premium; container and sterility burden
Stable multidose injection	Validated preservative system with optimized buffer	Supports outpatient and veterinary use	Preservative toxicity and compatibility
Improved nasal spray	Low-irritation buffer, isotonicity control, device optimization	Differentiates dose delivery and patient experience	Device and clinical bridging requirements
Preservative-free nasal spray	Unit-dose or advanced multidose container	Addresses local tolerability and preservative concerns	Higher packaging cost and microbial-control requirements
Mucoadhesive nasal product	Low-level bioadhesive polymer	May extend residence time or reduce dose loss	Irritation, altered pharmacokinetics, slower onset
Buccal or sublingual product	Permeation-enhancing and saliva-compatible excipients	May avoid injections and improve administration	Opioid exposure variability and abuse concerns
Veterinary injectable	Species-compatible buffer, preservative, and container system	Supports differentiated animal-health positioning	Species-specific safety and residue requirements
Long-acting depot	Biodegradable polymer or in situ gel	Could create a high-value product	Major clinical and regulatory program; opioid safety concerns

A conventional aqueous injection has the lowest technical risk. A differentiated intranasal or transmucosal formulation has greater value potential but requires more extensive pharmacokinetic and clinical support.

What formulations are protected by butorphanol tartrate patents?

The active molecule and tartrate salt are mature technologies. Butorphanol was developed decades ago, and basic composition-of-matter and salt protection are not expected to provide meaningful current U.S. exclusivity.

Potentially relevant rights may instead cover:

• Intranasal delivery systems.
• Spray pump architecture.
• Metered-dose containers.
• Specific concentration or pH ranges.
• Mucoadhesive formulations.
• Sustained-release matrices.
• Combination products.
• Methods of treating a defined patient population.
• Abuse-deterrent or tamper-resistant presentations.

Patent protection must be assessed claim by claim and jurisdiction by jurisdiction. A formulation patent is commercially useful only if its claims cover a necessary feature of the marketed product and survive validity and infringement challenges.

How strong is the patent estate for butorphanol tartrate?

The estate is likely weak for the unmodified active ingredient and standard aqueous injection. It can be stronger for a genuinely differentiated route or device, particularly where the formulation has:

1. A defined excipient range tied to improved stability or absorption.
2. A device limitation that competitors cannot easily design around.
3. Clinical evidence linking the formulation to a measurable benefit.
4. Claims covering both composition and method of use.
5. A realistic manufacturing barrier.

A patent claiming only a broad combination of butorphanol, water, salt, and buffer would face substantial obviousness and enablement risk. Narrow claims supported by comparative stability, nasal absorption, irritation, or dose-uniformity data have better enforcement prospects.

When does butorphanol tartrate lose exclusivity?

The core U.S. exclusivity period for butorphanol tartrate has expired. The product is not dependent on a modern new chemical entity exclusivity period, and the active ingredient is available through established generic pathways.

Exclusivity category	Status
New chemical entity exclusivity	Expired
Basic compound patent	Expired or commercially irrelevant
Basic salt protection	Expired or commercially irrelevant
Standard injectable generic entry	Established
Biosimilar exclusivity	Not applicable
Potential residual protection	Product-specific formulation, device, method, or patent rights

The practical market question is not when the active ingredient loses exclusivity. It is whether a new product can obtain regulatory differentiation and patent protection around administration, tolerability, pharmacokinetics, or packaging.

What is the Orange Book status of butorphanol tartrate?

The FDA Orange Book is the controlling source for current listed human drug products, reference products, therapeutic-equivalence evaluations, patents, and exclusivity information. Butorphanol tartrate injection has historically been marketed through generic application pathways, while the former branded nasal product, Stadol NS, has been discontinued in the United States according to FDA product-status records and commercial labeling sources.[1-3]

Orange Book analysis should distinguish:

• Currently marketed injectable products.
• Discontinued branded nasal products.
• Therapeutically equivalent generic products.
• Listed patents that remain relevant to an approved application.
• Delisted or expired patent information.
• Application status, which may differ from product availability.

A discontinued reference product can complicate a new nasal development program. The sponsor may need to establish the regulatory reference framework through FDA consultation rather than assume that an older marketed product remains an available commercial comparator.

Which companies are challenging butorphanol tartrate?

Generic competition has historically come from manufacturers of injectable butorphanol tartrate products. The commercial market is fragmented and includes generic pharmaceutical companies and contract manufacturers. The identity of current active applicants and market participants changes over time and should be verified against FDA Drugs@FDA, the Orange Book, and current labeling records.[1,2]

There is no biosimilar competitive pathway because butorphanol tartrate is a small-molecule drug. Competition is more likely to arise through:

• ANDA-approved injectable products.
• Reintroduced intranasal products.
• Veterinary products.
• Compounded or institutional formulations where legally permitted.
• Alternative opioid and nonopioid analgesics.

Paragraph IV litigation is most relevant to newly filed formulation, device, or method patents. It is unlikely to be central to the original active ingredient because foundational protection has expired. A 505(b)(2) sponsor with a new nasal or extended-release formulation could face Paragraph IV challenges if it lists patents in the Orange Book and a later applicant certifies that the patents are invalid, unenforceable, or not infringed.

What patent litigation and settlement risks affect the product?

The main litigation risks are formulation and device disputes rather than active-ingredient disputes.

Likely litigation triggers

• A new nasal spray claims a dose-metering mechanism similar to an incumbent device.
• A competitor uses the same narrow excipient range for nasal retention.
• A patent claims a specific treatment population or dosing regimen.
• A generic applicant challenges listed method-of-use patents.
• A sponsor asserts trade-secret protection over manufacturing controls that are difficult to distinguish from routine formulation practice.

Settlement agreements could delay entry, permit an authorized generic, or divide markets by dosage form. Any settlement involving a controlled opioid would also face heightened business, compliance, and reputational scrutiny. A patent settlement should be assessed for entry date, supply rights, authorized-generic provisions, and restrictions on alternative formulations.

What FDA regulatory pathway applies to new butorphanol formulations?

A standard injectable equivalent would generally pursue an ANDA if the applicant can demonstrate pharmaceutical equivalence, bioequivalence, and compliance with applicable quality requirements.

A new route, formulation, device, or clinical use may require a 505(b)(2) application. That pathway can rely partly on FDA findings for a listed drug while requiring new data for the proposed differences. The evidence burden rises with the degree of change.

Development type	Likely pathway	Evidence burden
Equivalent injectable vial	ANDA	Pharmaceutical equivalence, bioequivalence, CMC
Preservative-free equivalent	ANDA or 505(b)(2), depending on differences	CMC plus comparative data
New nasal spray	505(b)(2) likely	PK, local tolerability, device performance, CMC
New transmucosal product	505(b)(2) or NDA	PK, safety, efficacy, abuse-risk assessment
Veterinary reformulation	NADA or supplemental NADA	Species-specific safety, efficacy, CMC
Long-acting injectable	505(b)(2) or NDA	Extensive PK, safety, efficacy, CMC

The opioid designation increases scrutiny of abuse potential, diversion controls, labeling, and postmarket surveillance. A product that increases exposure duration or convenience could create commercial value while also increasing regulatory concern.

What manufacturing and intellectual-property barriers exist?

Butorphanol tartrate itself is not a major manufacturing barrier. The principal barriers are process control, sterile manufacturing, device integration, and regulatory documentation.

Key manufacturing risks

• Sterile filtration and aseptic filling for injections.
• Control of pH drift and degradation products.
• Container closure integrity.
• Adsorption or precipitation in delivery components.
• Preservative effectiveness in multidose products.
• Nasal pump dose uniformity over shelf life.
• Extractables and leachables from plastics and elastomers.
• Scale-up of low-dose metering systems.
• Controlled-substance inventory and security controls.

A nasal device can create a stronger commercial barrier than the excipient itself. Reliable actuation, priming, plume geometry, and residual volume affect the delivered dose and may support device or combination-product claims.

What commercial opportunities exist for butorphanol tartrate?

Human injectable products

The injectable market is a volume and supply-reliability opportunity, not a high-margin innovation market. A sponsor can compete through:

• Reliable availability.
• Ready-to-administer packaging.
• Preservative-free single-dose vials.
• Low extractables packaging.
• Hospital-friendly labeling.
• Prefilled syringes, where regulatory and compatibility requirements are met.

Intranasal rescue or acute-care products

Intranasal butorphanol could be positioned around needle-free administration, rapid onset, or use where intravenous access is impractical. The main commercial challenge is competition from established intranasal opioids and nonopioid rescue products, including naloxone-related products in opioid-focused channels.

A new butorphanol nasal product would need a clear reason to exist. A lower-irritation formulation, improved device, reduced administration burden, or better storage profile would be more defensible than a simple reformulation.

Veterinary products

Veterinary medicine is the strongest adjacent opportunity. Species-specific products can be differentiated through:

• Low-volume dosing.
• Convenient vial sizes.
• Improved syringeability.
• Preservative strategy suitable for repeated use.
• Stable formulations for mixed clinical environments.
• Packaging designed for controlled-substance reconciliation.
• Companion-animal and equine use cases.

Veterinary development still requires species-specific evidence. Human formulation data cannot be assumed to establish safety or efficacy in animals.

Licensing opportunities

Licensing value is most likely to arise from:

• A validated nasal or buccal delivery platform.
• A preservative-free multidose container.
• A proprietary metering pump.
• A long-acting injectable platform.
• A veterinary commercialization network.
• A manufacturing partner with controlled-substance capacity.

A licensee will usually discount an excipient-only asset unless the formulation has comparative clinical data, issued claims, freedom-to-operate analysis, and a practical manufacturing process.

How does butorphanol tartrate compare with competing opioid products?

Factor	Butorphanol tartrate	Morphine	Nalbuphine	Fentanyl
Market maturity	Mature	Mature	Mature	Mature but highly differentiated
Biosimilar risk	None	None	None	None
Generic pressure	High	High	High	High
Nasal opportunity	Historically established	Limited by product	Limited	Stronger competitive field
Excipient differentiation	Moderate	Moderate	Moderate	High regulatory sensitivity
Abuse and diversion scrutiny	High	High	High	Very high
Best commercial angle	Delivery and veterinary use	Cost and hospital supply	Clinical positioning	Device, route, and rescue use

Butorphanol’s mixed receptor profile may support clinical positioning in selected settings, but it also limits broad substitution claims. Product strategy should focus on route, workflow, tolerability, and supply reliability rather than assuming pharmacology alone will create a premium market.

Key Takeaways

• Butorphanol tartrate has no meaningful remaining basic-molecule exclusivity.
• Standard aqueous injection is technically straightforward and commercially price-sensitive.
• Preservative-free injection and improved packaging offer the lowest-risk differentiation.
• Intranasal and transmucosal products offer greater value but require stronger clinical, device, and regulatory support.
• Formulation patents should tie specific excipients to measurable stability, absorption, tolerability, or dose-delivery benefits.
• Veterinary formulations are a credible adjacent opportunity with species-specific regulatory requirements.
• There is no biosimilar pathway; competition comes from generics, alternative opioids, and new delivery systems.
• The strongest defensible asset would combine a differentiated formulation, a proprietary device, clinical performance data, and a scalable controlled-substance manufacturing process.

FAQs

Can a new excipient alone extend exclusivity for butorphanol tartrate?

Usually not. A new excipient may support a patent only when it produces a non-obvious and measurable technical effect, such as improved stability, absorption, tolerability, or dose consistency.

Is preservative-free butorphanol injection commercially attractive?

It can be attractive in hospitals and repeated-use settings, but the premium must offset low generic pricing, sterile manufacturing costs, and the need to demonstrate a practical benefit.

Can butorphanol tartrate be developed as a 505(b)(2) product?

Yes. A new route, device, formulation, dosing regimen, or clinical use may support a 505(b)(2) application if the sponsor supplies the data needed for the proposed differences.

Are butorphanol nasal spray patents likely to block a new entrant?

Older nasal-spray patents may be expired or commercially weak, but device, formulation, and method-of-use patents can still create freedom-to-operate risks. Current patent records require product-specific review.

What is the most investable butorphanol tartrate opportunity?

A differentiated veterinary or intranasal product with a proprietary delivery system is more investable than another conventional injectable. The asset should have issued or pending claims, comparative pharmacokinetic data, and a clear regulatory pathway.

References

1. U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
3. DailyMed. (n.d.). Butorphanol tartrate injection prescribing information. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/
4. U.S. Food and Drug Administration. (n.d.). 505(b)(2) applications. https://www.fda.gov/drugs/types-applications/abbreviated-new-drug-application-anda/505b2-applications
5. U.S. Food and Drug Administration. (n.d.). Controlled substances act and FDA-regulated products. https://www.fda.gov/drugs/drug-scheduling-controls/controlled-substances-act-csa-and-fda-regulated-products