List of Excipients in Branded Drug ATAZANAVIR SULFATE

Generic Drugs Containing ATAZANAVIR SULFATE

Company	Ingredient	NDC	Excipient
Teva Pharmaceuticals USA Inc	atazanavir sulfate	0093-5526	CROSPOVIDONE
Teva Pharmaceuticals USA Inc	atazanavir sulfate	0093-5526	D&C YELLOW NO. 10 ALUMINUM LAKE
Teva Pharmaceuticals USA Inc	atazanavir sulfate	0093-5526	FD&C BLUE NO. 1
Teva Pharmaceuticals USA Inc	atazanavir sulfate	0093-5526	FD&C BLUE NO. 1 ALUMINUM LAKE
Teva Pharmaceuticals USA Inc	atazanavir sulfate	0093-5526	FD&C BLUE NO. 2--ALUMINUM LAKE

What are the Most Frequently-Used Excipients in ATAZANAVIR SULFATE?

# Of NDCs	Excipient
6	CROSPOVIDONE
1	D&C YELLOW NO. 10
1	D&C YELLOW NO. 10 ALUMINUM LAKE
2	FD&C BLUE NO. 1
1	FD&C BLUE NO. 1 ALUMINUM LAKE

Atazanavir Sulfate Excipient Strategy and Commercial Opportunities

Last updated: September 24, 2026

Atazanavir sulfate is an orally administered HIV-1 protease inhibitor with a formulation profile driven by poor aqueous solubility, pH-dependent absorption, food effects, and substantial interaction with acid-reducing agents. The strongest excipient opportunities are pH-modifying systems, precipitation-control technologies, pediatric taste-masked powders, lower-pill-burden dosage forms, and fixed-dose combination platforms. The original Reyataz patent and regulatory exclusivity positions have largely expired, so commercial protection now depends on differentiated formulations, manufacturing know-how, device integration, and narrow method-of-use or product claims rather than the active ingredient itself.

What is the FDA regulatory status of atazanavir sulfate?

Atazanavir sulfate is the sulfate salt of atazanavir, marketed originally by Bristol-Myers Squibb under the brand name Reyataz. The FDA approved Reyataz capsules in 2003 for use with other antiretroviral agents in the treatment of HIV-1 infection. The FDA later approved an oral powder formulation for pediatric patients and patients unable to swallow capsules. [1]

Attribute	Atazanavir sulfate
Brand	Reyataz
Original sponsor	Bristol-Myers Squibb
Drug class	HIV-1 protease inhibitor
Route	Oral
Dosage forms	Capsules; oral powder
Primary indication	HIV-1 infection
FDA approval	2003 for capsules
Key formulation issue	pH-dependent solubility and absorption
Current regulatory pathway	ANDA-based generic competition
Biosimilar risk	Not applicable; atazanavir is a small molecule

Atazanavir is generally administered once daily when used with pharmacokinetic boosting or in specified treatment regimens. The recommended dose varies according to age, treatment history, coadministered agents, renal or hepatic status, and whether ritonavir or cobicistat is used. [1]

What is the Orange Book status of Reyataz?

Reyataz has been subject to Orange Book-listed patents and regulatory exclusivities associated with the original active ingredient, pharmaceutical composition, and use. Those protections have expired or reached the end of their commercial relevance for standard atazanavir sulfate capsules. Generic atazanavir sulfate products have entered the U.S. market through abbreviated new drug applications.

The commercial consequence is material: a new atazanavir product generally cannot rely on blocking generic entry through the original compound patent. A sponsor must instead pursue an improved formulation, pediatric presentation, combination product, manufacturing process, or clinically differentiated use.

How does atazanavir sulfate solubility affect excipient selection?

Atazanavir is a weakly basic compound whose solubility increases in acidic conditions and declines as gastric pH rises. Proton-pump inhibitors, H2-receptor antagonists, and antacids can reduce exposure. This creates a direct formulation requirement: the dosage form must promote dissolution in the stomach while limiting precipitation as the drug moves into the higher-pH intestinal environment.

The main formulation risks are:

1. Incomplete dissolution from low intrinsic solubility.
2. Variable absorption caused by gastric pH.
3. Drug precipitation after pH increases.
4. Food-dependent changes in exposure.
5. Interaction with acid-reducing medicines.
6. Dose-size and capsule-burden constraints.
7. Poor palatability in pediatric formulations.

The sulfate salt provides a practical solid-state form for oral delivery, but salt selection alone does not remove pH-related performance risks. Excipients must control wetting, microenvironmental pH, dispersion, and precipitation.

What excipient classes are most suitable for atazanavir sulfate?

Acidifying and microenvironmental pH modifiers

Organic acids can maintain an acidic microenvironment during wetting and dissolution. Candidate excipients include citric acid, fumaric acid, malic acid, tartaric acid, and succinic acid. Selection depends on compatibility, hygroscopicity, taste, processability, and the target dissolution profile.

An acidifier may improve dissolution in a capsule or powder, but excess acidity can create stability, tolerability, or manufacturing problems. The commercial value is highest where the excipient system produces a reproducible dissolution advantage without requiring a separate acid-reducing protective package.

Wetting and solubilizing agents

Surfactants and wetting agents can improve contact between atazanavir sulfate and gastrointestinal fluids. Candidate materials include sodium lauryl sulfate, poloxamers, polysorbates, and selected lipid-based excipients.

Surfactant use must be controlled. High concentrations can affect gastrointestinal tolerability, capsule integrity, powder flow, and dissolution reproducibility. A low-level surfactant combined with an acidifier and a precipitation inhibitor may provide a more defensible platform than a surfactant-only formulation.

Polymers and precipitation inhibitors

Hydrophilic polymers can maintain supersaturation after the drug encounters a higher-pH environment. Candidate excipients include:

• Hypromellose
• Hydroxypropyl cellulose
• Polyvinylpyrrolidone
• Copovidone
• Soluplus-type graft copolymers
• Hydroxypropyl methylcellulose acetate succinate in specialized dispersions

These polymers can inhibit crystal growth and precipitation. Their selection should be based on biorelevant dissolution, supersaturation duration, drug-polymer miscibility, and the effect on tablet compression or powder redispersion.

Disintegrants and wicking agents

Crospovidone, sodium starch glycolate, croscarmellose sodium, and low-substituted hydroxypropyl cellulose can accelerate liquid penetration and dosage-form breakup. Crospovidone is particularly useful where rapid dispersion is needed without excessive gel formation.

For a high-dose or compressed formulation, disintegrant level must be balanced against tablet hardness and friability. For capsules, a free-flowing blend with rapid dispersion may be more commercially attractive than a large tablet.

Lipid-based excipients

Self-emulsifying or self-microemulsifying systems can improve delivery of poorly soluble drugs. Suitable components may include medium-chain triglycerides, mono- and diglycerides, polyethylene glycol esters, and nonionic surfactants.

A lipid system could support a softgel or liquid-filled capsule, but it introduces new risks involving fill compatibility, leakage, oxidation, shell interaction, and scale-up. It is a higher-complexity option than an acidified solid oral formulation.

Taste-masking and suspension excipients

For pediatric oral powder or liquid products, taste-masking is a central development issue. Candidate tools include:

• Sweeteners such as sucrose, sucralose, or acesulfame potassium
• Flavors
• Xanthan gum or other suspending agents
• Hydroxypropyl cellulose
• Ion-exchange resins
• Polymer coatings
• Lipid or multiparticulate barriers

Atazanavir bitterness can limit adherence. A powder that disperses rapidly, masks bitterness, and remains stable after reconstitution could compete with existing capsule and powder products even without a major change in dose.

What formulations are protected by the original Reyataz product strategy?

Reyataz was commercialized primarily as hard capsules and later as an oral powder. The labeled capsule excipient system includes conventional materials such as lactose monohydrate, crospovidone, and magnesium stearate, with gelatin-based capsule shells and colorants. The oral powder uses a different excipient architecture directed toward dispersion, suspension, palatability, and pediatric administration. [1,2]

The original product strategy did not depend on a modern amorphous solid dispersion or sophisticated lipid delivery system. That leaves room for later entrants to pursue:

• Amorphous atazanavir sulfate dispersions
• Acidified multiparticulates
• pH-triggered release capsules
• Taste-masked pediatric granules
• Sprinkle formulations
• Orally disintegrating tablets
• Liquid-filled capsules
• Fixed-dose combinations
• Low-dose boosted formulations
• Co-packaged antiretroviral regimens

A formulation patent would need claims that distinguish the product through composition, process, dissolution performance, particle engineering, or clinical effect. Broad claims covering routine excipient combinations would face invalidity and obviousness pressure.

Which commercial formulation opportunities exist for atazanavir sulfate?

Pediatric powder and granules

The most direct opportunity is an improved pediatric dosage form. A product could compete through better taste, longer post-reconstitution stability, smaller administration volume, reduced dosing steps, or compatibility with common foods and beverages.

The oral powder market is narrower than the adult capsule market, but pediatric adherence and supply reliability can support premium pricing, institutional contracts, and public-sector procurement.

Acid-reducing-agent-tolerant formulations

Atazanavir exposure is sensitive to gastric acid suppression. A formulation designed to reduce this dependency could address a meaningful clinical limitation. Potential approaches include:

• Stronger microenvironmental acidification
• Enteric protection followed by targeted release
• Supersaturating dispersion systems
• Coformulation with a controlled acidifying excipient
• Gastric-retentive systems

The development burden is high because the sponsor must establish performance under different gastric pH conditions and demonstrate that the product does not create unacceptable pharmacokinetic variability.

Fixed-dose combinations

Combination therapy is commercially attractive because it reduces pill burden. Atazanavir may be evaluated in combination with ritonavir, cobicistat, nucleoside reverse transcriptase inhibitors, or other antiretroviral agents.

The main technical barriers are excipient compatibility, dose alignment, pharmacokinetic interaction, and regulatory complexity. A combination product would need to preserve atazanavir dissolution while avoiding interaction with the other active ingredients.

Orally disintegrating and sprinkle products

An orally disintegrating tablet or sprinkle capsule could improve administration for patients with swallowing difficulty. The main challenges are the drug's dose, taste, and need for pH-sensitive dissolution.

Multiparticulates are commercially attractive because they can separate acidifying, taste-masking, and release-control functions across different particle populations.

Long-acting or implantable delivery

Long-acting delivery is a less immediate opportunity. Atazanavir's physicochemical properties, required exposure, and historical use as an oral protease inhibitor make a depot product technically difficult. A long-acting injectable would compete with established long-acting HIV therapies and would require substantial clinical development. It is therefore a high-risk, high-investment strategy rather than a near-term excipient opportunity.

How strong is the patent estate for atazanavir sulfate?

The original compound and product patent estate is commercially weak against new entrants because core protection has expired or is no longer sufficient to prevent ordinary generic competition. The remaining value is concentrated in narrower rights.

IP category	Current commercial value
Atazanavir active ingredient	Low; core protection expired
Sulfate salt as a broad concept	Low to moderate, depending on claim scope and jurisdiction
Conventional capsule excipients	Low
Pediatric powder composition	Moderate if claims are narrow and technically supported
Amorphous dispersion	Moderate to high if stability and bioavailability are demonstrated
pH-modifying system	Moderate
Manufacturing process	Moderate, particularly where difficult to reverse engineer
Fixed-dose combination	Moderate to high, subject to combination-specific claims
Method of use	Narrow and indication-dependent
Device or administration system	Moderate

Patent strength depends on claim breadth, written-description support, freedom-to-operate risk, prior art, and the ability to identify infringement through routine product testing. Process patents are more difficult to enforce when manufacturing occurs outside the United States or when the process cannot be inferred from the finished product.

When does atazanavir sulfate lose exclusivity?

The original U.S. market exclusivity period has ended. FDA-approved generic atazanavir sulfate products are available, and ordinary capsule products face established generic competition. The exact status of individual strengths, manufacturers, and marketing availability is reflected in current FDA product databases and the Orange Book. [3]

Unlike biologics, atazanavir does not face biosimilar substitution. Competition occurs through ANDAs, authorized generic arrangements, direct branded-generic substitution, and differentiated dosage forms.

Which companies are challenging or competing with Reyataz?

Competition has come primarily from generic manufacturers filing ANDAs for atazanavir sulfate capsules. The market may include multiple approved applicants, but active commercial supply varies by strength, contracting arrangements, procurement demand, and manufacturing economics.

The competitive set includes:

• Generic capsule manufacturers
• Authorized or licensed suppliers
• HIV-focused specialty manufacturers
• Contract development and manufacturing organizations
• Sponsors developing pediatric or combination products
• Suppliers of formulation technologies for poorly soluble drugs

The most defensible commercial position is unlikely to come from another standard capsule. A differentiated product needs a defined clinical or operational advantage, such as easier administration, better stability, lower storage burden, improved taste, or improved performance during acid-reducing therapy.

What generic launch risks exist for a new atazanavir formulation?

A new formulation faces five major risks.

First, standard generics establish a low reference price. A sponsor must show why payers, clinicians, hospitals, or procurement agencies should adopt the differentiated product.

Second, atazanavir is an older antiretroviral. HIV treatment guidelines increasingly favor newer regimens with strong tolerability, resistance, and interaction profiles. A formulation improvement does not eliminate therapeutic-area substitution risk.

Third, a new formulation may trigger a clinical bridging requirement. Bioequivalence under fed and fasted conditions may not be sufficient if the sponsor claims reduced pH sensitivity, improved adherence, or a new pediatric use.

Fourth, excipient changes can alter pharmacokinetics. A pH modifier or lipid system may change exposure enough to create safety or dose-adjustment concerns.

Fifth, procurement channels can favor low-cost generic capsules. Public-sector tenders may not pay for convenience unless the product solves a documented administration or supply problem.

How does atazanavir compare with other HIV protease inhibitors?

Product	Formulation profile	Commercial implication
Atazanavir sulfate	pH-dependent solubility; capsule and powder products	Strong opportunity for pH-control and pediatric technologies
Darunavir	Typically administered with a booster; tablet and suspension options	Larger modern commercial base but strong competitive pressure
Lopinavir/ritonavir	Historically available as solution and tablets	Established pediatric and liquid experience
Fosamprenavir	Prodrug-based oral formulation	Less direct formulation comparability
Saquinavir	Older protease inhibitor with complex dosing	Lower current commercial attractiveness

Atazanavir's once-daily positioning and established pediatric powder history support targeted formulation opportunities. Its interaction with gastric acid suppression and aging treatment status limit the addressable market.

What licensing deals could create value?

Licensing opportunities are most credible in four areas:

1. A proven amorphous dispersion platform with atazanavir-specific dissolution and pharmacokinetic data.
2. A pediatric taste-masking technology that supports a stable sprinkle or granule product.
3. A fixed-dose combination platform with compatible antiretroviral actives.
4. A manufacturing process that reduces solvent use, improves yield, or controls particle size and solid form.

A license should be evaluated against the remaining commercial life of the product, the number of generic competitors, regulatory bridging costs, and whether the rights cover the United States, European Union, low- and middle-income markets, or procurement-focused territories.

What geographic markets offer the best opportunities?

The United States and Western Europe have the strongest regulatory infrastructure but also the most generic price pressure. Emerging markets may offer larger unmet needs for pediatric, heat-stable, and simplified dosage forms, particularly where HIV treatment programs procure through tenders.

Geographic value may be higher for:

• Countries with limited pediatric formulation supply
• Markets where oral powder logistics are weak
• Regions with high rates of acid-reducing-agent use
• Public-sector programs seeking lower pill burden
• Countries where local manufacturing or technology transfer is required

A global strategy should separate high-margin differentiated products from low-cost tender products. The same excipient system may require different packaging, stability data, and regulatory documentation by region.

What manufacturing and IP barriers affect commercialization?

Key manufacturing barriers include:

• Control of particle size and solid-state form
• Uniform distribution of low-dose excipients
• Moisture control
• Acidifier compatibility
• Capsule-fill weight variation
• Powder segregation
• Taste-mask coating uniformity
• Scale-up of amorphous dispersions
• Stability under tropical conditions
• Reconstitution performance for pediatric products

The strongest manufacturing IP often relates to process parameters rather than ingredient identity. A process that reliably produces a stable supersaturating dispersion or a consistent coated multiparticulate may provide more practical protection than a broad excipient claim.

Key Takeaways

• Atazanavir sulfate is a weakly basic, pH-sensitive oral drug with poor-solubility formulation challenges.
• The original Reyataz exclusivity position has largely expired, and standard capsules face generic competition.
• The highest-value excipient strategies involve microenvironmental acidification, precipitation inhibition, taste masking, and multiparticulate delivery.
• Pediatric powders, sprinkle products, and acid-reducing-agent-tolerant formulations offer the clearest differentiated opportunities.
• Fixed-dose combinations may provide commercial value but carry substantial compatibility and regulatory risks.
• Conventional lactose-crospovidone-magnesium stearate capsule systems are unlikely to support meaningful new patent protection alone.
• Process patents, formulation-performance claims, and device-linked claims are more defensible than broad conventional excipient claims.
• Biosimilar risk is irrelevant because atazanavir is a small-molecule drug; generic ANDA competition is the relevant pathway.
• Market attractiveness is constrained by the age of the product and competition from newer HIV regimens.
• A commercially viable program needs a measurable advantage in administration, stability, pharmacokinetics, or procurement economics.

FAQs

Can atazanavir sulfate be formulated as an amorphous solid dispersion?

Yes. An amorphous dispersion could improve apparent solubility and delay precipitation, but the formulation would require strong physical-stability controls and biorelevant dissolution data.

Is lactose a suitable excipient for atazanavir sulfate?

Lactose is suitable in conventional capsule systems and is used in the original product formulation. It may be unsuitable for a differentiated product if lactose intolerance, moisture sensitivity, or a low-carbohydrate positioning is commercially important.

Can atazanavir sulfate be developed as an oral liquid?

Yes, but the product would need control of sedimentation, taste, chemical stability, dose uniformity, and post-reconstitution shelf life. A suspension or powder-for-reconstitution product is more practical than a simple aqueous solution.

Does atazanavir sulfate require a pH modifier in every formulation?

No. A pH modifier is not mandatory for every dosage form, but pH control is a central development consideration because solubility and absorption are strongly affected by gastric acidity.

Is a new atazanavir sulfate formulation eligible for three-year FDA exclusivity?

Potentially, if it receives approval based on new clinical investigations essential to approval and meets statutory requirements. A formulation change supported only by routine pharmaceutical development may not qualify.

References

1. U.S. Food and Drug Administration. (2024). Reyataz (atazanavir sulfate) prescribing information. Bristol-Myers Squibb Company.

2. National Library of Medicine. (2024). DailyMed: Reyataz, atazanavir sulfate capsule and oral powder labeling. U.S. National Library of Medicine.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.