List of Excipients in Branded Drug ALFENTANIL HYDROCHLORIDE

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Akorn	ALFENTANIL HYDROCHLORIDE	alfentanil hydrochloride	17478-067	SODIUM CHLORIDE
Akorn	ALFENTANIL HYDROCHLORIDE	alfentanil hydrochloride	17478-067	WATER

Generic Drugs Containing ALFENTANIL HYDROCHLORIDE

Company	Ingredient	NDC	Excipient
Hospira Inc	alfentanil hydrochloride	0409-2266	SODIUM CHLORIDE
Hospira Inc	alfentanil hydrochloride	0409-2266	WATER

What are the Most Frequently-Used Excipients in ALFENTANIL HYDROCHLORIDE?

# Of NDCs	Excipient
1	SODIUM CHLORIDE
1	WATER

Alfentanil Hydrochloride Excipient Strategy and Commercial Opportunities

Last updated: September 3, 2026

Alfentanil hydrochloride is an established, short-acting opioid anesthetic with limited current product differentiation. The commercial opportunity is concentrated in sterile injectable products that improve hospital workflow, dosing accuracy, storage efficiency, and supply reliability. The strongest formulation strategy is a preservative-free aqueous injection using a minimal excipient system, supported by ready-to-administer presentations such as prefilled syringes and standardized concentration vials.

What is the commercial status of alfentanil hydrochloride?

Alfentanil hydrochloride is a synthetic opioid analgesic used primarily as an intravenous adjunct to general anesthesia. It has rapid onset and short duration because of relatively rapid redistribution and clearance compared with longer-acting fentanyl products. The drug is administered under controlled-substance restrictions in the United States.[1]

The historical U.S. reference product was Alfenta, an injectable product associated with Janssen Pharmaceutica. The commercial product was supplied as a sterile solution, generally at concentrations of 500 micrograms/mL and 5 mg/10 mL, depending on presentation and market configuration.[1]

Attribute	Alfentanil hydrochloride
Therapeutic class	Opioid analgesic; anesthetic adjunct
Route	Intravenous injection
Primary setting	Operating room and procedural anesthesia
Dosage form	Sterile aqueous injection
Controlled-substance status	Schedule II in the United States
Biosimilar exposure	None; alfentanil is a small molecule
Main competitive products	Fentanyl, remifentanil, sufentanil, and other short-acting anesthetic opioids
Core commercial constraint	Small and specialized hospital market with controlled-substance handling requirements

Commercial demand is narrower than for fentanyl because alfentanil is used mainly in anesthesia protocols requiring rapid titration. That specialization can support premium positioning only when the product reduces preparation time, minimizes calculation errors, or improves availability.

What excipients are used in alfentanil hydrochloride injection?

The established formulation is a simple aqueous injectable system. The active ingredient is alfentanil hydrochloride, with sodium chloride used for isotonicity and water for injection as the vehicle. The product pH is adjusted with acid and base, historically including sulfuric acid and sodium hydroxide.[1]

A representative excipient architecture is:

Formulation function	Likely excipient or component	Commercial purpose
Vehicle	Water for injection	Dissolves active ingredient and supports parenteral administration
Tonicity adjustment	Sodium chloride	Reduces hemolysis and improves injection tolerability
pH adjustment	Sodium hydroxide and/or sulfuric acid	Controls pH and supports chemical stability
Container closure	Glass vial, ampoule, or polymer syringe system	Protects sterility and supports administration
Nitrogen headspace, where used	Nitrogen	May reduce oxidative exposure during storage

A low-excipient formulation is commercially preferable because the product is administered intravenously, often to anesthetized patients, and has limited tolerance for unnecessary formulation complexity. Preservatives, surfactants, cosolvents, and antioxidant systems should not be added unless supported by stability, compatibility, and regulatory data.

What pH range should an alfentanil injection target?

The target pH should be based on the reference product, forced-degradation studies, injection-site tolerability, and container-closure compatibility. The historical product was formulated as an acidic aqueous solution. A generic or improved product should match the reference product's clinically acceptable pH range as closely as practicable rather than pursue an unvalidated neutral-pH formulation.

pH optimization should assess:

• Alfentanil hydrolysis and degradation products.
• Precipitation risk after dilution into common infusion fluids.
• Compatibility with polypropylene syringes and polyvinyl chloride tubing.
• Adsorption to administration sets.
• Local tolerability during intravenous administration.
• Stability after withdrawal from the primary container.

The pH-adjusting agents are unlikely to create meaningful intellectual-property differentiation. Their value is functional and regulatory: they help establish a stable, isotonic, injectable product.

What formulation strategy is strongest for alfentanil hydrochloride?

The strongest base strategy is a preservative-free, ready-to-use aqueous injection in a standardized concentration. The product should minimize bedside manipulation and support rapid anesthetic dosing.

Strategy 1: Standardized single-dose vial

A single-dose vial is the lowest-risk development route. It can closely replicate the historical formulation and support an ANDA where a suitable reference product and regulatory pathway are available.

Advantages include:

• Familiar hospital handling.
• Straightforward sterile manufacturing.
• Low excipient burden.
• Simple comparative formulation work.
• Lower packaging complexity than a prefilled syringe.

The main weakness is that clinicians must withdraw the drug into a syringe, creating preparation steps and potential dose-selection errors.

Strategy 2: Ready-to-administer prefilled syringe

A prefilled syringe offers the clearest commercial differentiation. It can reduce preparation time, standardize concentration, and limit open-container handling. The formulation must be evaluated against syringe barrel materials, elastomeric components, silicone oil, needle systems, and terminal sterilization or aseptic-processing requirements.

A prefilled syringe is most attractive when it provides:

• A fixed, clinically familiar dose.
• Clear labeling for controlled-substance administration.
• Tamper-evident packaging.
• Low dead volume.
• Reliable plunger performance after storage.
• Compatibility with anesthesia carts and automated documentation systems.

The principal risks are extractables and leachables, drug adsorption, particulate formation, stopper interaction, and a more demanding combination-product or device review.

Strategy 3: High-concentration presentation

A higher-concentration vial or syringe could reduce injection volume, but this is a higher-risk strategy. It may create a new dosage form or concentration that cannot rely on a simple bioequivalence argument. The product would need strong justification for clinical utility and may require additional pharmacokinetic, safety, or usability evidence.

Potential use cases include procedures requiring high opioid potency with limited injection volume. The commercial market is likely narrower than for a standard concentration unless the product solves a specific anesthesia workflow problem.

Strategy 4: Diluted infusion presentation

A premixed infusion bag is technically possible but commercially less compelling. Alfentanil is generally administered in carefully titrated anesthetic settings, where dose control and short-duration use favor syringes or small-volume vials. A premixed bag increases logistics, packaging volume, and stability requirements.

What excipient opportunities can create commercial differentiation?

Excipient innovation alone is unlikely to generate strong patent protection for alfentanil hydrochloride. Commercial differentiation is more likely to come from the complete presentation, including concentration, container, delivery device, labeling, and workflow integration.

Preservative-free formulation

A preservative-free formulation is appropriate for intravenous anesthesia and can support single-dose use. It avoids concerns associated with antimicrobial preservatives in vulnerable patients and is consistent with the established injectable use pattern.

The commercial benefit is strongest when paired with a single-use vial or prefilled syringe. A preservative-free claim by itself is unlikely to create durable market exclusivity.

Low-sorption formulation

Alfentanil is a potent drug administered at low concentrations. Adsorption to tubing, syringes, and infusion components can affect delivered dose, particularly during dilution or low-flow administration. A formulation and packaging package that demonstrates lower drug loss could support hospital adoption.

The development program should quantify recovery after contact with:

• Polyvinyl chloride tubing.
• Polypropylene syringes.
• Low-density polyethylene components.
• Silicone-lubricated syringes.
• Common stopcocks and extension sets.
• Infusion bags and filters.

A low-sorption claim must be supported by validated analytical recovery testing under clinically relevant conditions. It is more likely to support product differentiation than a novel buffer system.

Nitrogen-protected packaging

If oxidative degradation is observed, nitrogen headspace or oxygen-controlled filling may improve shelf life. This approach adds manufacturing controls but does not necessarily require a new excipient. It may be useful for a product seeking a longer shelf life or broader storage conditions.

The value depends on actual degradation pathways. Nitrogen should not be used as a substitute for adequate pH control, container selection, and light protection.

Low-particulate and low-volume presentation

An injection designed for clean withdrawal, low residual volume, and low particulate burden can improve operating-room handling. This is a device and packaging opportunity more than an excipient opportunity.

Potential configurations include:

• Low-volume glass vials.
• Ready-to-administer syringes.
• Luer-lock systems.
• Barcoded unit-dose packaging.
• Clear labeling of microgram-per-mL concentration.
• Tamper-evident controlled-substance packaging.

What FDA regulatory pathway applies to alfentanil hydrochloride products?

A conventional generic injectable would generally be evaluated through the ANDA pathway if a suitable reference listed drug, dosage form, strength, and product-specific guidance support that route.[2] A materially different formulation, delivery system, concentration, or clinical use could require a 505(b)(2) application rather than a standard ANDA.

The regulatory burden depends on the degree of difference from the reference product.

Product concept	Likely regulatory posture	Principal evidence
Same concentration, route, and qualitative formulation	ANDA-oriented	Pharmaceutical equivalence, bioequivalence or comparative evidence, sterility, stability
Same drug with different container or syringe	ANDA or 505(b)(2), depending on product design	Device compatibility, extractables and leachables, usability, comparative quality
New concentration	Potentially 505(b)(2)	Dose justification, safety, pharmacokinetics, clinical rationale
Premixed infusion	Potentially 505(b)(2)	Stability after dilution, administration compatibility, clinical-use justification
Novel excipient system	Potentially 505(b)(2)	Safety and compatibility package for the excipient system

For sterile injectables, FDA review focuses heavily on aseptic processing, container-closure integrity, particulate matter, bacterial endotoxins, sterility, extractables and leachables, and stability. Controlled-substance security and diversion controls are also material to commercial launch planning.[2,3]

What is the Orange Book status of alfentanil hydrochloride?

Alfentanil hydrochloride is a small-molecule drug and is not subject to biosimilar regulation. Orange Book analysis should focus on the reference product, any listed patents, therapeutic-equivalence codes, and the status of approved abbreviated applications.[2]

The historical formulation and use patents for alfentanil are old relative to the product's commercial history. Basic composition-of-matter and original formulation barriers are therefore unlikely to remain commercially relevant in the United States. The more important current barriers are regulatory, manufacturing, controlled-substance compliance, and market size.

Potential residual patent issues could involve:

• A specific prefilled syringe configuration.
• A concentrated presentation.
• A ready-to-administer anesthesia system.
• A narrow method of use.
• A combination with a delivery device.
• A manufacturing process or packaging configuration.

A conventional aqueous vial that follows the historical product is less likely to encounter meaningful patent exclusion than a differentiated device or formulation. Any launch decision still requires a current patent and Orange Book review for the target jurisdiction and product configuration.

When does alfentanil hydrochloride lose exclusivity?

The original commercial exclusivity for alfentanil hydrochloride expired long ago. The active ingredient is therefore generally viewed as an off-patent generic opportunity rather than a protected innovator asset.

The relevant exclusivity question is no longer the expiration of the original alfentanil molecule patent. It is whether a new product configuration can obtain limited regulatory exclusivity or enforceable patent protection.

Potential sources of later exclusivity include:

• A new clinical indication.
• A novel delivery system.
• A new dosage form.
• A qualifying orphan indication.
• A patent covering a specific device or formulation.
• A regulatory exclusivity period associated with a 505(b)(2) product, if applicable.

These opportunities are difficult to justify in a small anesthesia market unless the product addresses a documented clinical or operational problem.

Which companies are challenging alfentanil hydrochloride?

Competition is likely to come from generic injectable manufacturers and established anesthesia suppliers rather than from biosimilar developers. The principal competitive products are fentanyl citrate, remifentanil hydrochloride, sufentanil citrate, and other short-acting opioid anesthetics.

Competitor	Relative commercial position	Competitive advantage
Fentanyl citrate	Broad hospital use	Familiarity, extensive supply base, low cost
Remifentanil hydrochloride	Strong short-acting anesthesia position	Very rapid offset and titratability
Sufentanil citrate	High potency anesthesia use	Potency and established procedural use
Alfentanil hydrochloride	Specialized use	Rapid onset and short duration
Non-opioid adjuncts	Growing protocol role	Opioid-sparing anesthesia strategies

Alfentanil is not likely to win on price alone. A supplier needs dependable availability, clear concentration labeling, low preparation burden, and a formulation that fits operating-room protocols.

What generic entry risks exist for alfentanil hydrochloride?

Generic entry risk is high from an intellectual-property perspective for a conventional vial because the molecule and core injectable formulation are mature. The commercial risk is different: demand may be too limited to support several manufacturers, and controlled-substance obligations may reduce the number of willing entrants.

Key entry barriers include:

1. Small addressable market. The product is used mainly in anesthesia and procedural care.
2. Controlled-substance compliance. Manufacturing, distribution, quota management, diversion controls, and recordkeeping add cost.
3. Sterile manufacturing capacity. Injectable products require qualified facilities and robust inspection readiness.
4. Supply reliability. Hospital buyers may favor suppliers with established injectable portfolios.
5. Low switching tolerance. Anesthesia departments may resist changes in concentration, labeling, or presentation.
6. Limited pricing power. A conventional generic vial can face rapid price compression.
7. Reference-product complications. The availability and regulatory status of the reference product affect the ANDA strategy.

A first-to-market or supply-secure launch may have value even without meaningful patent protection. That value depends on manufacturing cost, procurement contracts, and the ability to avoid shortages.

What formulation patents could protect alfentanil hydrochloride?

The most plausible patentable areas are secondary products rather than the basic drug solution. Potential claims could cover:

• A stable ready-to-use syringe formulation.
• A defined pH and concentration range with demonstrated stability.
• A low-adsorption container-closure system.
• A specific prefilled syringe and administration method.
• A unit-dose product with barcode and controlled-substance safeguards.
• A formulation that remains stable after dilution into a specified infusion vehicle.
• A manufacturing process that reduces impurities or particulate formation.
• A long-term storage package using a defined polymer, elastomer, or oxygen-control system.

Patent strength would depend on unexpected technical results. A claim limited to commonly used water, sodium chloride, acid, and base would likely be vulnerable to obviousness challenges. A stronger filing would connect the formulation to measurable benefits such as improved recovery, reduced adsorption, longer stability, reduced impurity formation, or superior container compatibility.

What manufacturing and intellectual-property barriers affect alfentanil products?

Manufacturing barriers are more significant than core composition patents. A viable product requires:

• A qualified sterile injectable facility.
• Validated aseptic processing.
• Controlled-substance licenses and security systems.
• Reliable alfentanil hydrochloride API supply.
• Container-closure integrity testing.
• Extractables and leachables data.
• Stability data in the proposed market package.
• Validated assays for potency, impurities, and degradation products.
• Supply-chain controls appropriate for Schedule II distribution.

API sourcing can become a competitive barrier if only a small number of suppliers produce pharmaceutical-grade alfentanil hydrochloride. Dual sourcing may be difficult but can materially improve hospital contracting and shortage resilience.

What licensing deals could support alfentanil hydrochloride commercialization?

A licensing transaction would be most logical for a differentiated presentation rather than a basic vial. Relevant counterparties include:

• A sterile injectable manufacturer with controlled-substance capability.
• A prefilled-syringe platform company.
• A hospital-focused generic supplier.
• An anesthesia portfolio company.
• A contract development and manufacturing organization with Schedule II handling authorization.

Deal value would depend on whether the partner contributes an approved facility, an existing regulatory dossier, a hospital sales channel, or a protected delivery system. A conventional formulation without market exclusivity is more likely to support a supply, contract-manufacturing, or distribution agreement than a high-value asset license.

What revenue exposure and commercial opportunities exist?

The opportunity is niche but potentially defensible in selected hospital channels. The most attractive products are likely:

1. A reliable generic vial replacing an intermittently available product.
2. A ready-to-administer syringe that reduces operating-room preparation.
3. A standardized concentration that minimizes dosing errors.
4. A dual-sourced product for hospital groups seeking supply security.
5. A bundled anesthesia portfolio offering with fentanyl, remifentanil, or sufentanil.

Revenue exposure is sensitive to tender pricing and hospital group purchasing. The product should be modeled as a specialty injectable with modest unit volume, limited consumer demand, and high importance of supply continuity. A premium price requires evidence of operational savings or better availability.

How does alfentanil compare with remifentanil and fentanyl?

Alfentanil occupies an intermediate commercial position. Fentanyl has broader use and stronger purchasing leverage. Remifentanil has a highly differentiated pharmacokinetic profile and remains attractive where rapid offset is central to the anesthesia protocol.

Criterion	Alfentanil	Fentanyl	Remifentanil
Onset	Rapid	Rapid	Very rapid
Duration	Short	Longer than alfentanil	Very short
Cost pressure	High	Very high	Variable
Market breadth	Narrow	Broad	Specialized
Formulation opportunity	Prefilled syringe and standardized vial	Broad injectable portfolio	Ready-to-use and infusion systems
Main differentiation	Rapid titration with established anesthesia use	Familiarity and cost	Predictable rapid offset

Alfentanil's commercial case is strongest where its pharmacology is already embedded in local anesthesia practice and the supplier can offer consistent stock, clear dosing, and low preparation burden.

Key Takeaways

• Alfentanil hydrochloride is an old, off-patent small-molecule anesthetic with no biosimilar exposure.
• The base formulation is a simple preservative-free aqueous injection using water for injection, sodium chloride, and pH-adjusting agents.
• A conventional vial has limited patent differentiation and faces price pressure.
• The strongest commercial opportunity is a ready-to-administer prefilled syringe or highly standardized single-dose presentation.
• Low adsorption, container compatibility, particulate control, and stability after dilution are important development priorities.
• Controlled-substance compliance and sterile manufacturing capacity are more important barriers than the original alfentanil patent estate.
• A 505(b)(2) strategy may be relevant for a new concentration, delivery system, or materially differentiated formulation.
• Commercial success depends on hospital workflow, supply reliability, anesthesia portfolio integration, and procurement access.

FAQs

Is alfentanil hydrochloride still protected by composition-of-matter patents?

No. The original composition-of-matter and core product protections are historic. Current risk is more likely to involve a specific device, concentration, formulation, or method of use.

Can alfentanil hydrochloride be formulated without sodium chloride?

Yes, but removal of sodium chloride would require a justified isotonicity strategy and comparative quality and tolerability data. A reformulation should not assume that a different tonicity system will receive the same regulatory treatment as the established product.

Is a prefilled alfentanil syringe likely to receive patent protection?

It may receive protection if the syringe, formulation, packaging, or use method has a non-obvious technical feature with measured benefits. A standard drug-filled syringe with routine components is less likely to support strong patent claims.

Does alfentanil hydrochloride have biosimilar competition?

No. Alfentanil hydrochloride is a small molecule. Competition would arise through generic injectable applications and differentiated delivery presentations.

What is the best first product for a new alfentanil manufacturer?

A preservative-free, standard-concentration single-dose vial is usually the lowest-risk entry product. A prefilled syringe is the stronger commercial product if the manufacturer can support device development, controlled-substance compliance, and a higher-quality hospital value proposition.

References

1. Janssen Pharmaceutica. (n.d.). Alfenta (alfentanil hydrochloride injection) prescribing information. U.S. Food and Drug Administration labeling archive.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA, Center for Drug Evaluation and Research.

3. U.S. Food and Drug Administration. (2024). Sterile drug products produced by aseptic processing: Current good manufacturing practice. FDA, Center for Drug Evaluation and Research.

4. U.S. Drug Enforcement Administration. (2024). Controlled substances act, Schedule II substances. U.S. Department of Justice.

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