List of Excipients in Branded Drug PENTOBARBITAL SODIUM

Generic Drugs Containing PENTOBARBITAL SODIUM

Company	Ingredient	NDC	Excipient
Akorn	pentobarbital sodium	17478-181	ALCOHOL
Akorn	pentobarbital sodium	17478-181	HYDROCHLORIC ACID
Akorn	pentobarbital sodium	17478-181	PROPYLENE GLYCOL
Akorn	pentobarbital sodium	17478-181	SODIUM HYDROXIDE
Akorn	pentobarbital sodium	17478-181	WATER
Hikma Pharmaceuticals USA Inc	pentobarbital sodium	24201-010	ALCOHOL
Hikma Pharmaceuticals USA Inc	pentobarbital sodium	24201-010	PROPYLENE GLYCOL

What are the Most Frequently-Used Excipients in PENTOBARBITAL SODIUM?

# Of NDCs	Excipient
3	ALCOHOL
2	HYDROCHLORIC ACID
3	PROPYLENE GLYCOL
2	SODIUM HYDROXIDE
3	WATER

Last updated: August 16, 2026

Pentobarbital sodium is an off-patent, tightly controlled barbiturate with limited conventional pharmaceutical growth prospects. The strongest excipient opportunities are formulation upgrades rather than new chemical entities: lower-toxicity injectable vehicles, ready-to-use presentations, improved container compatibility, oral taste masking, and animal-health products designed for controlled administration. Commercial access is constrained by Schedule II controls in the United States, restricted distribution, procurement scrutiny, and a narrow approved-use market.

Pentobarbital Sodium Excipient Strategy and Commercial Opportunities

What is the commercial status of pentobarbital sodium?

Pentobarbital sodium is the water-soluble sodium salt of pentobarbital, a short- to intermediate-acting barbiturate. It has been used as a sedative, hypnotic, anticonvulsant, anesthetic adjunct, and euthanasia agent. In the United States, pentobarbital is a Schedule II controlled substance under the Controlled Substances Act.[1]

The product is commercially relevant in three principal settings:

Market	Typical dosage form	Commercial position
Human hospital use	Sterile injectable solution	Restricted, low-volume institutional market
Veterinary medicine	Injectable solution and other controlled presentations	More commercially active than human outpatient use
Research and specialty use	Controlled liquid or injectable formats	Small, highly regulated market

Pentobarbital sodium is off patent as an active pharmaceutical ingredient. The commercial value is concentrated in manufacturing authorization, controlled-substance distribution, formulation quality, supply reliability, and customer access rather than basic molecule ownership.

Historically marketed Nembutal products established the reference formulation, but current supply is primarily associated with generic or specialty manufacturers. Product availability, label status, and distribution vary by jurisdiction and time. FDA labeling and DailyMed records identify approved or marketed presentations and their excipient compositions.[2,3]

What excipients are used in pentobarbital sodium formulations?

The principal excipient issue is solubilization. Pentobarbital sodium is highly water soluble relative to the free acid, but concentrated injectable products require a mixed-solvent system to maintain clarity, stability, and acceptable handling.

Injectable formulation excipients

Commercial pentobarbital sodium injections commonly use:

• Water for Injection
• Propylene glycol
• Ethanol
• Sodium hydroxide or hydrochloric acid for pH adjustment
• In some products, preservatives or other stabilizing components

A representative injectable formulation contains pentobarbital sodium in a high-pH aqueous system with propylene glycol and alcohol as cosolvents.[2,3] The exact composition depends on the manufacturer, concentration, container, and regulatory filing.

The formulation creates several technical constraints:

1. Propylene glycol can cause injection-site pain, hyperosmolarity, and systemic toxicity at high exposure.
2. Ethanol can create tolerability, labeling, and handling concerns.
3. High pH can affect tissue tolerability and compatibility with elastomeric closures.
4. Concentrated solutions can precipitate after dilution or temperature changes.
5. Sorption and extractables may become relevant with plastic syringes, infusion sets, and storage containers.

Oral formulation excipients

Oral pentobarbital sodium capsules and liquid preparations may use conventional excipients such as:

• Lactose or other fillers
• Starch-based disintegrants
• Magnesium stearate
• Talc
• Gelatin capsule shells
• Purified water
• Sweeteners, flavors, and viscosity agents in liquids

The commercial challenge for oral products is less solubility than dose uniformity, palatability, controlled dispensing, and prevention of accidental exposure. A formulation intended for veterinary use may prioritize rapid administration and tamper-resistant packaging over patient acceptability.

Which excipient strategies have the greatest commercial potential?

The highest-value opportunities involve reducing formulation liabilities while preserving the established route of administration.

1. Reduced-solvent injectable systems

A lower-propylene-glycol formulation could reduce injection-site discomfort and systemic solvent exposure. Potential approaches include:

• Higher-efficiency cosolvent combinations
• Complexation or cyclodextrin systems
• pH optimization
• Concentration adjustment
• Co-solvent replacement with lower-toxicity pharmaceutical solvents
• Improved sodium-salt crystallinity and particle control

The main regulatory barrier is demonstrating that the revised excipient system does not alter pharmacokinetics, local tolerability, precipitation behavior, or dosing reliability. Because pentobarbital is a narrow-therapeutic-index controlled drug, formulation changes would require careful comparative testing.

2. Ready-to-use hospital and veterinary presentations

Ready-to-use prefilled syringes, unit-dose vials, or closed-system bags could reduce preparation errors and occupational exposure. This opportunity is most relevant where institutions administer pentobarbital under emergency, anesthesia, or euthanasia protocols.

Potential formats include:

• Single-dose prefilled syringes
• Low-volume vials
• Barcode-enabled unit-dose packaging
• Tamper-evident veterinary syringes
• Closed-transfer systems
• Dilution-stable infusion containers

The value proposition is operational. The product would compete on availability, dose accuracy, reduced manipulation, and controlled inventory management rather than price alone.

3. Container-closure and compatibility systems

Pentobarbital sodium solutions are alkaline and solvent-containing. Primary packaging therefore has a material impact on stability and usability.

Relevant development areas include:

• Low-extractable glass vials
• Fluoropolymer-coated elastomeric stoppers
• Low-sorption syringe components
• Compatibility with polypropylene and cyclic olefin polymer systems
• Improved protection from light and temperature excursions
• Reduced leachables from seals and administration sets

A container-closure package supported by strong extractables and leachables data could create a practical differentiation platform for generic manufacturers.

4. Oral taste masking and controlled dispensing

Oral liquid pentobarbital products face bitterness, dosing errors, and diversion risk. Excipient opportunities include:

• Ion-exchange resin complexes
• Lipid or polymeric taste-masking systems
• High-viscosity suspensions
• Unit-dose oral syringes
• Child-resistant and tamper-evident packaging
• Colorants or flavor systems compatible with controlled-drug labeling

Taste masking must not delay absorption materially or create dose nonuniformity. The strongest commercial application is veterinary medicine, where liquid administration may be preferred but palatability and handling remain operational problems.

What formulation patents could protect pentobarbital sodium products?

Pentobarbital sodium itself has no meaningful modern composition-of-matter exclusivity. A new patent position would likely depend on formulation or device claims.

Potentially protectable subject matter includes:

Patent category	Example claim focus	Commercial value
Solvent system	Defined propylene glycol, ethanol, water, and pH ranges	Moderate if performance improves
Low-toxicity injection	Reduced solvent burden with maintained solubility	High if clinically meaningful
Stabilized solution	Resistance to precipitation or degradation	Moderate
Container system	Specific syringe, stopper, or coated vial	Moderate
Oral delivery	Taste-masked liquid or capsule	Moderate in veterinary markets
Unit-dose device	Controlled dispensing or tamper resistance	Moderate
Manufacturing process	Crystallization, filtration, or aseptic filling process	Limited unless difficult to design around
Method of use	Specific sedation or euthanasia protocol	Narrow and commercially dependent on jurisdiction

A formulation patent would need more than the substitution of one conventional excipient for another. Stronger claims would connect a defined composition with measurable advantages such as:

• Reduced precipitation after dilution
• Lower injection-site irritation
• Improved shelf life
• Lower impurity formation
• Reduced adsorption to administration equipment
• Consistent delivered dose
• Improved stability across temperature ranges

Because the active ingredient is old, obviousness risk is substantial. A patent strategy should combine composition claims, concentration ranges, pH limits, container claims, and process claims where the data support each category.

When does pentobarbital sodium lose exclusivity?

Pentobarbital sodium has already lost traditional small-molecule exclusivity. The relevant commercial protections are regulatory approvals, manufacturing controls, controlled-substance permissions, supply contracts, and any later-filed formulation or device patents.

Exclusivity type	Pentobarbital sodium position
Composition-of-matter patent	Expired
Original product patent	Expired or commercially irrelevant
Generic entry	Established historically
New chemical entity exclusivity	Not applicable to the mature molecule
Orphan-drug exclusivity	Not a general protection for current pentobarbital products
Pediatric exclusivity	Product-specific and not a general market barrier
Formulation exclusivity	Possible only through later approvals or patents
Controlled-substance authorization	Operational requirement, not market exclusivity

For a new formulation, the regulatory pathway could create limited product-specific protection, but the commercial life would depend on the extent of formulation differentiation and whether competitors can use another excipient system.

What is the FDA and Orange Book status of pentobarbital sodium?

FDA status is presentation-specific. Pentobarbital sodium products have been listed in FDA databases and labeling repositories in injectable and oral forms, but active marketing status can differ from historical approval status.[2,3]

The Orange Book is relevant for identifying listed patents and exclusivity associated with approved drug products. For an old generic product, the expected patent burden is low. A prospective manufacturer should distinguish among:

• FDA-approved product listings
• Current commercial availability
• Discontinued products
• Abbreviated New Drug Application status
• Orange Book patent listings
• DailyMed labeling
• DEA registration and ordering requirements

A formulation company should not assume that a historical Nembutal label proves current commercial availability. The operative questions are whether an approved application remains active, whether a manufacturer is currently supplying the product, and whether the proposed product requires a new application or a supplemental change.

Are Paragraph IV challenges relevant to pentobarbital sodium?

Paragraph IV litigation is unlikely to be a central risk for conventional pentobarbital sodium products because the core molecule and legacy formulations are long established. A Paragraph IV filing could arise if a new branded formulation obtained listed patents covering:

• A novel injectable vehicle
• A depot or modified-release dosage form
• A device-assisted presentation
• A protected oral delivery system
• A specific stabilized composition

For a conventional generic injectable, the greater risks are regulatory and operational:

• Failure to demonstrate sterile manufacturing control
• Inadequate extractables and leachables data
• Incompatibility with administration equipment
• Incomplete controlled-substance procedures
• Inability to secure reliable API supply
• Product interruption caused by limited manufacturing capacity

Which companies are competing in the pentobarbital sodium market?

The competitive market includes generic pharmaceutical manufacturers, specialty injectable companies, veterinary suppliers, and distributors authorized to handle controlled substances. The precise supplier group changes as products are discontinued, relaunched, or transferred between manufacturers.

Competition is shaped by five factors:

1. DEA-controlled procurement and inventory requirements.
2. Limited institutional demand in human medicine.
3. Veterinary demand for reliable injectable supply.
4. High regulatory burden for sterile manufacturing.
5. Customer preference for dependable availability over minor price differences.

A formulation supplier can participate without marketing the active drug by selling:

• Pharmaceutical-grade cosolvents
• Low-extractable packaging
• Prefilled syringe components
• Taste-masking excipient platforms
• Stability-indicating analytical methods
• Controlled-drug packaging systems
• Contract development and manufacturing services

What manufacturing and intellectual-property barriers affect commercial entry?

The largest barrier is not patent exclusion. It is the combination of controlled-substance compliance and sterile injectable manufacturing.

API and process barriers

Pentobarbital sodium manufacturing requires control of:

• Assay and impurity profile
• Sodium conversion and crystallization
• Residual solvents
• Particle burden
• Water content
• Microbial quality
• Aseptic processing
• Stability under alkaline conditions

A process patent may provide limited protection, but manufacturing know-how can still create a meaningful practical barrier. Reliable sterile filling at low commercial volumes is particularly important because the market may not support multiple high-capacity producers.

Distribution barriers

United States suppliers must manage DEA registration, procurement quotas, security controls, records, audits, theft prevention, and disposal procedures.[1] These obligations increase fixed costs and discourage opportunistic entrants.

Geographic coverage

The United States is the most restrictive major market because of controlled-substance rules and heightened scrutiny of pentobarbital distribution. European and other markets apply separate narcotics, medicinal-product, veterinary, and euthanasia controls. A formulation platform must be evaluated against region-specific excipient permissions, labeling requirements, packaging rules, and controlled-drug distribution laws.

How does pentobarbital sodium compare with competing sedative and euthanasia products?

Product category	Main advantage	Excipient opportunity	Commercial constraint
Pentobarbital sodium injection	Established effect and rapid administration	Lower-solvent, ready-to-use, compatibility systems	Schedule II control and supply restrictions
Phenobarbital products	Longer duration and established oral use	Taste masking and controlled-release formulations	Less suitable for rapid procedural use
Propofol injection	Rapid onset and short recovery	Emulsion stability and antimicrobial control	Different clinical profile and storage burden
Veterinary euthanasia combinations	Familiar administration protocols	Palatability, viscosity, and dosing devices	Animal-health regulatory requirements
Benzodiazepine-based sedation	Broad procedural use	Solubilization and low-volume delivery	Does not replicate pentobarbital’s full use profile

Pentobarbital’s formulation opportunity is strongest where its established pharmacology matters and where customers experience solvent burden, supply interruptions, or administration risk.

What revenue exposure and launch scenarios exist?

Pentobarbital sodium is unlikely to support a large mass-market launch. Revenue potential is more credible in specialized supply niches.

Launch scenario	Product concept	Revenue profile	Risk
Generic injectable	Conventional vial	Low to moderate	Price competition and controlled distribution
Premium injectable	Lower-solvent or improved compatibility	Moderate	Clinical and regulatory evidence burden
Ready-to-use product	Prefilled syringe or unit dose	Moderate	Device, stability, and controlled-substance controls
Veterinary liquid	Taste-masked or easier-to-administer product	Moderate	Market access and diversion controls
Excipient platform licensing	Vehicle, packaging, or taste masking	Moderate	Requires multiple licensees
Global specialty supply	Region-specific controlled product	Variable	Different narcotics regulations

The most attractive business model may be licensing an enabling formulation or packaging technology to an approved manufacturer rather than independently commercializing pentobarbital sodium.

How strong is the patent estate for pentobarbital sodium?

The legacy patent estate is weak. The molecule is mature, generic competition exists, and conventional excipient combinations are vulnerable to obviousness challenges.

A new patent estate could be stronger if it includes:

• A non-obvious solvent architecture
• Demonstrated reduction in toxicity or local irritation
• A clinically useful concentration not previously enabled
• A validated container-closure interaction solution
• A device that reduces controlled-drug handling risk
• Data showing improved stability after dilution or temperature stress

Patent strength would remain moderate at best unless the formulation produces a clear, reproducible, and commercially important advantage. Freedom-to-operate analysis should focus on later formulation patents, device patents, and packaging claims rather than expired compound patents.

Key Takeaways

• Pentobarbital sodium is an off-patent, Schedule II barbiturate with a narrow but persistent institutional and veterinary market.
• The main excipient problem is the high-solvent, alkaline injectable formulation.
• The strongest development opportunities are reduced-solvent injections, ready-to-use presentations, low-extractable packaging, and taste-masked oral products.
• Conventional excipient substitutions are unlikely to produce strong patent protection without comparative performance data.
• Controlled-substance distribution, sterile manufacturing, and reliable API supply are greater entry barriers than legacy patents.
• A licensing strategy focused on formulation, packaging, or delivery technology may be more attractive than a standalone drug launch.
• Generic entry risk is high for conventional products but lower for differentiated presentations supported by formulation or device patents.
• FDA approval, DailyMed labeling, Orange Book records, and DEA authorization must be assessed at the specific product and manufacturer level.

Frequently Asked Questions

Can propylene glycol be removed from pentobarbital sodium injection?

It may be technically possible, but removal requires a replacement solubilization strategy and comparative testing for clarity, precipitation, stability, tolerability, and delivered dose. A simple water-only formulation is unlikely to support the same concentration and shelf life.

Is pentobarbital sodium suitable for a new extended-release formulation?

The molecule could be evaluated for modified release, but the commercial rationale is limited. Extended-release delivery would require a new pharmacokinetic and safety package and would compete with established sedative and anticonvulsant therapies.

What excipient has the greatest near-term value for pentobarbital sodium?

The highest near-term value is likely in a formulation or packaging system that reduces solvent exposure, improves container compatibility, or enables a reliable ready-to-use dose. The opportunity is operational rather than broad consumer demand.

Can veterinary pentobarbital sodium products use human pharmaceutical excipients?

They may use the same excipients if the formulation meets applicable veterinary regulatory, quality, safety, and labeling requirements. Human-product precedent does not automatically establish approval for an animal-health product.

Does pentobarbital sodium require a new patent to be commercially attractive?

No. A manufacturer can compete through an approved generic product, supply reliability, packaging, or distribution. A new patent becomes commercially important only when it protects a differentiated formulation, delivery device, or manufacturing process that competitors cannot easily design around.

References

1. U.S. Drug Enforcement Administration. (2024). Controlled substances act: Schedule II substances and regulatory requirements. U.S. Department of Justice.

2. U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drug products containing pentobarbital sodium. U.S. Department of Health and Human Services.

3. National Library of Medicine. (2024). DailyMed: Pentobarbital sodium injection labeling and inactive ingredient information. U.S. National Library of Medicine.

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

5. United States Pharmacopeial Convention. (2024). United States Pharmacopeia and National Formulary: Pentobarbital sodium and pharmaceutical excipient standards. USP Convention.