List of Excipients in Branded Drug ANAGRELIDE HYDROCHLORIDE

Generic Drugs Containing ANAGRELIDE HYDROCHLORIDE

Company	Ingredient	NDC	Excipient
Teva Pharmaceuticals USA Inc	anagrelide hydrochloride	0172-5241	ANHYDROUS LACTOSE
Teva Pharmaceuticals USA Inc	anagrelide hydrochloride	0172-5241	CELLULOSE, MICROCRYSTALLINE
Teva Pharmaceuticals USA Inc	anagrelide hydrochloride	0172-5241	CROSPOVIDONE
Teva Pharmaceuticals USA Inc	anagrelide hydrochloride	0172-5241	D&C YELLOW NO. 10 ALUMINUM LAKE
Teva Pharmaceuticals USA Inc	anagrelide hydrochloride	0172-5241	FD&C BLUE NO. 1 ALUMINUM LAKE
Teva Pharmaceuticals USA Inc	anagrelide hydrochloride	0172-5241	FD&C BLUE NO. 2--ALUMINUM LAKE

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

# Of NDCs	Excipient
2	ALUMINUM OXIDE
3	ANHYDROUS LACTOSE
3	CELLULOSE, MICROCRYSTALLINE
3	CROSPOVIDONE
2	D&C YELLOW NO. 10
1	D&C YELLOW NO. 10 ALUMINUM LAKE

Anagrelide Hydrochloride Excipient Strategy and Commercial Opportunities

Last updated: September 27, 2026

Anagrelide hydrochloride is a small-molecule, orally administered platelet-lowering drug used primarily for essential thrombocythemia. The commercial market is genericized, and the strongest opportunities are formulation execution, low-dose content uniformity, excipient differentiation, supply reliability, and regional regulatory expansion rather than compound patent exclusivity.

The product is generally supplied as 0.5 mg and 1 mg capsules. Common inactive ingredients include lactose, povidone, crospovidone, and magnesium stearate, with gelatin-based capsule shells and colorants varying by manufacturer.[1,2] Because the active dose is low and treatment is chronic, excipient selection directly affects blend uniformity, dissolution, stability, capsule fill weight, and manufacturing cost.

What is anagrelide hydrochloride used for?

Anagrelide hydrochloride reduces elevated platelet counts in patients with essential thrombocythemia. It is also used in selected patients with other myeloproliferative neoplasms when platelet reduction is clinically required.

Anagrelide inhibits megakaryocyte maturation and platelet production. It also inhibits phosphodiesterase III, which contributes to cardiovascular adverse effects such as palpitations, tachycardia, headache, and fluid retention.[1]

Attribute	Product characteristic
Active ingredient	Anagrelide hydrochloride
Active moiety	Anagrelide
Therapeutic class	Platelet-lowering agent
Primary indication	Essential thrombocythemia
Dosage form	Immediate-release oral capsule
Common strengths	0.5 mg and 1 mg
Administration	Usually divided oral dosing
Market type	Genericized small-molecule market
Biosimilar exposure	None
Key formulation issue	Low-dose uniformity and tolerable, reproducible release

The low dose creates a higher formulation risk than the capsule size suggests. A 0.5 mg capsule may contain a relatively small quantity of active pharmaceutical ingredient compared with the excipient mass. Poor powder flow, segregation, electrostatic charging, or inadequate blending can create significant potency variation.

What excipients are used in anagrelide hydrochloride capsules?

Commercial anagrelide capsules commonly use a conventional immediate-release excipient system. FDA labeling for marketed products identifies lactose, povidone, crospovidone, and magnesium stearate among the inactive ingredients, although the exact composition differs by manufacturer and strength.[1,2]

Excipient category	Typical role	Commercial rationale
Lactose monohydrate or another diluent	Increases capsule fill mass and supports blend uniformity	Low cost, established regulatory history, good availability
Povidone	Binder and wet-granulation aid	Improves granule strength and active distribution
Crospovidone	Superdisintegrant	Supports rapid capsule opening and dispersion
Magnesium stearate	Lubricant	Improves ejection and manufacturing flow
Gelatin	Hard capsule shell	Established oral dosage form with broad supply base
Titanium dioxide and colorants	Opacity and product identification	Supports strength differentiation and branding

The specific product label should control any excipient comparison because capsule colors, shell materials, printing inks, and colorants can vary. Generic manufacturers also may use anhydrous lactose, microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide, hypromellose, or plant-based capsule shells, subject to regulatory acceptance and demonstrated equivalence.

How should anagrelide hydrochloride excipients be selected?

The best excipient strategy prioritizes dose uniformity, rapid and reproducible dissolution, low manufacturing variability, and a clean regulatory profile.

Diluent strategy

Lactose is commercially attractive because it is inexpensive and widely used in oral solid dosage forms. It can support acceptable blend properties when the anagrelide particle size and surface characteristics are controlled.

A lactose-free formulation can create a secondary opportunity for patients with lactose intolerance, formulary preferences, or excipient restrictions. Microcrystalline cellulose, mannitol, dibasic calcium phosphate, or spray-dried composite excipients are potential substitutes. Each option changes bulk density, flow, lubrication demand, dissolution, and capsule fill weight.

Mannitol can support a differentiated, lactose-free formulation with a neutral taste profile and good water solubility. Microcrystalline cellulose is widely available and robust, but excessive use may slow or alter disintegration depending on grade and compression behavior. Dibasic calcium phosphate can improve flow but may introduce pH and density considerations.

Binder and granulation strategy

Povidone is a conventional binder for wet granulation. It can help distribute a low-dose active ingredient throughout the powder bed. Excessive binder concentration or high-viscosity grades may produce hard granules and slower dissolution.

Dry granulation or roller compaction may reduce water exposure and simplify scale-up. The approach can be useful if anagrelide hydrochloride has moisture sensitivity or if wet processing creates degradation or polymorphic concerns. It can also reduce process steps, but roller compaction may increase fines and segregation risk.

Direct blending is possible where the active ingredient has suitable flow and particle-size characteristics. It is less forgiving when the API is cohesive, electrostatic, or present at a very low percentage of the final blend.

Disintegrant strategy

Crospovidone is consistent with an immediate-release capsule strategy. The target is rapid dispersion without creating excessive fines or poor blend flow. Sodium starch glycolate and croscarmellose sodium are alternative options, but each can change water uptake, swelling, dissolution, and sensitivity to lubricant concentration.

A development program should evaluate disintegration and dissolution after accelerated stability, not only at release. Lubricant overmixing can reduce wetting and delay dissolution, particularly in low-dose formulations with high specific surface area.

Lubricant and glidant strategy

Magnesium stearate is cost-effective and widely accepted. Its main development risks are over-lubrication, hydrophobic film formation, and dissolution slowing. Mixing time and shear should be controlled as critical process parameters.

Colloidal silicon dioxide may improve flow and reduce adhesion, but it can also alter bulk density and capsule fill behavior. Its use should be justified by measurable improvements in flow, content uniformity, or manufacturing robustness.

What formulations are protected by anagrelide patents?

The principal commercial opportunity is not based on an active compound patent. Anagrelide hydrochloride has been marketed for decades, and generic products are available in the United States. Compound and early formulation exclusivity have therefore expired or no longer provide a meaningful barrier to standard immediate-release capsules.[3,4]

Potentially protectable formulation concepts include:

• Lactose-free or gelatin-free capsules.
• Particle-engineered anagrelide hydrochloride.
• Controlled-release or extended-release delivery.
• Improved dissolution for poorly wetting API particles.
• Reduced peak-related cardiovascular adverse effects.
• Modified-release dosing intended to reduce dosing frequency.
• Stabilized formulations with improved moisture or oxygen resistance.
• Specific capsule fill compositions that improve content uniformity.
• Manufacturing processes that control polymorph, particle size, or agglomeration.

A patent on an excipient combination has commercial value only if it produces a measurable performance advantage and is difficult to design around. A basic substitution of lactose for microcrystalline cellulose usually has limited exclusionary strength unless linked to a defined dissolution, stability, bioavailability, or manufacturing result.

When does anagrelide hydrochloride lose exclusivity?

The meaningful U.S. market exclusivity period has already ended. Agrylin received FDA approval in the 1990s, and anagrelide hydrochloride is now available from generic manufacturers.[1,3]

Exclusivity issue	Current commercial implication
New chemical entity exclusivity	Expired
Orphan-drug exclusivity	Any original period has expired
Original compound patent protection	Expired or commercially immaterial
Standard immediate-release capsule	Open to ANDA competition
Formulation patents	Relevant only if separately issued and unexpired
Pediatric exclusivity	No current practical barrier to standard generic entry
Biosimilar exclusivity	Not applicable

The lack of a current compound barrier shifts value toward manufacturing reliability, regulatory execution, and differentiated product design.

What is the Orange Book status of anagrelide hydrochloride?

Anagrelide hydrochloride is an FDA-approved small molecule and is eligible for generic competition through the abbreviated new drug application pathway when the product meets applicable bioequivalence, pharmaceutical equivalence, and quality requirements.[3,5]

The Orange Book should be reviewed for the current reference-listed drug, active patents, and exclusivity codes before filing or acquisition. For a mature product such as anagrelide, the main regulatory questions are usually:

1. Whether the proposed product matches the reference in strength, dosage form, route, and active ingredient.
2. Whether the capsule composition creates a bioequivalence or dissolution issue.
3. Whether the proposed labeling is consistent with the reference product.
4. Whether any current patent listing affects certification strategy.
5. Whether the product is subject to current FDA guidance on product-specific bioequivalence.

A formulation that changes release characteristics or dosing frequency may fall outside a conventional ANDA strategy and could require a 505(b)(2) application.

Are there Paragraph IV challenges for anagrelide hydrochloride?

Paragraph IV litigation risk is limited for a mature, genericized product unless a new patent has been listed for a specific formulation, method of use, or delivery technology.

A standard immediate-release anagrelide capsule is more likely to face routine ANDA competition than meaningful patent litigation. Paragraph IV exposure may arise if a sponsor develops:

• A modified-release capsule.
• A novel particle-size or solid-state form.
• A formulation intended to reduce cardiovascular adverse events.
• A new indication or dosing regimen.
• A proprietary excipient system with an issued and listed patent.

The absence of a major current patent dispute does not eliminate regulatory risk. Generic applicants still face quality, bioequivalence, manufacturing, and supply-chain scrutiny.

What manufacturing and intellectual-property barriers affect anagrelide?

The most important barriers are technical rather than patent-based.

Low-dose content uniformity

Anagrelide hydrochloride must be distributed uniformly at low concentration. Critical variables include API particle-size distribution, bulk density, surface area, electrostatic behavior, blend order, sampling method, and segregation during transfer.

A manufacturer can create commercial value by developing a validated premix or ordered-mixture process. This may support higher batch yields, lower rejection rates, and more reliable 0.5 mg capsule production.

API sourcing

Anagrelide hydrochloride API supply may be more concentrated than supply for high-volume generic drugs. Vendor qualification, impurity control, polymorph management, and long-term supply contracts can materially affect market entry.

Stability and packaging

A stability program should evaluate moisture, oxygen, light, capsule-shell interaction, and extractables and leachables from packaging. Aluminum-aluminum blister packs may offer stronger moisture protection than high-density polyethylene bottles but can increase packaging cost.

Capsule shell choice

Gelatin remains the lowest-risk commercial option. Hypromellose or pullulan shells can support vegetarian, religious, or excipient-sensitive positioning. They may also change moisture behavior, mechanical strength, dissolution, and filling performance.

How strong is the anagrelide hydrochloride patent estate?

The patent estate is weak for the conventional immediate-release product and potentially stronger for genuinely differentiated delivery technologies.

Estate component	Relative strength
Core anagrelide compound	Low; mature and expired
Conventional capsule composition	Low
Lactose-free substitution alone	Low to moderate
Novel modified release	Moderate to strong if clinically meaningful
Adverse-event reduction technology	Moderate to strong if supported by data
Solid-state or particle-engineering claims	Moderate, dependent on claim scope
Manufacturing process claims	Moderate if process-specific and difficult to design around
New method-of-use claims	Variable and dependent on enforceability

A commercially useful patent should claim a specific composition or process, demonstrate an unexpected result, and limit easy substitution by competitors. Broad claims directed only to the presence of common excipients are vulnerable to invalidity and design-around arguments.

What generic entry opportunities exist for anagrelide hydrochloride?

Generic entry opportunities fall into four categories.

Low-cost standard generic

This approach uses a conventional excipient system and competes on price, supply, and regulatory reliability. It is the fastest route but has the lowest differentiation.

Lactose-free or vegetarian generic

A lactose-free, hypromellose-capsule product can target hospitals, specialty pharmacies, and patients with excipient restrictions. The commercial premium is likely limited unless supported by formulary demand or supply shortages.

Manufacturing-quality platform

A sponsor can differentiate through high content-uniformity performance, resilient API sourcing, low defect rates, and dependable supply. This is especially relevant to hospital and specialty-pharmacy channels.

505(b)(2) modified-release product

A once-daily or lower-peak formulation could command greater value if it reduces dosing burden or improves tolerability. The development cost and clinical evidence requirements would be materially higher than for an ANDA.

How does anagrelide compare with competing platelet-lowering drugs?

Hydroxyurea is commonly used in essential thrombocythemia and has a lower-cost generic profile. Pegylated interferon products may be used in selected patients, particularly where disease modification or treatment of younger patients is considered. Aspirin addresses thrombotic risk but does not replace platelet-lowering therapy where cytoreduction is required.

Product	Main commercial position	Excipient opportunity
Anagrelide hydrochloride	Oral platelet-lowering therapy	Low-dose capsule, lactose-free, modified release
Hydroxyurea	Low-cost oral cytoreductive therapy	Less attractive capsule differentiation; handling and safety controls matter
Pegylated interferon	Injectable specialty therapy	Device, formulation stability, and administration convenience
Aspirin	Antiplatelet adjunct	Limited relevance to anagrelide substitution

Anagrelide’s commercial weakness is cardiovascular tolerability and divided dosing. Its advantage is oral administration and a mechanism distinct from hydroxyurea. A formulation that reduces peak exposure without compromising platelet control could create a more defensible product.

What is the FDA regulatory pathway for a new anagrelide product?

A conventional immediate-release generic capsule would generally pursue an ANDA referencing the FDA reference-listed drug.[3,5] A product with a different release profile, new indication, or clinically meaningful delivery modification may require a 505(b)(2) application.

Key development work includes:

• Pharmaceutical equivalence.
• Comparative dissolution across relevant media and pH conditions.
• Assay and content uniformity.
• Impurity and degradation-product control.
• Stability under ICH conditions.
• In vitro-in vivo relationship assessment where applicable.
• Bioequivalence testing for the selected strength or strengths.
• Capsule-shell compatibility.
• Extractables and leachables evaluation.
• Process validation and continued process verification.

An excipient change that remains within a conventional immediate-release capsule may be manageable within an ANDA. A change that alters absorption, release rate, or clinical exposure can move the product into a more demanding regulatory pathway.

What is the commercial outlook and revenue exposure?

Anagrelide is a niche chronic-therapy market rather than a high-volume primary-care product. Revenue exposure is shaped by the size of the essential thrombocythemia population, generic price erosion, payer substitution, and supply continuity.

The most defensible revenue opportunities are:

1. Regional generic launches where fewer suppliers are approved.
2. Dual sourcing and contract manufacturing for existing marketers.
3. Shortage-resistant supply to specialty pharmacies and hospitals.
4. Lactose-free or gelatin-free products with targeted reimbursement positioning.
5. Modified-release products supported by clinical differentiation.
6. Licensing of formulation or manufacturing technology to established generic companies.

A standard capsule manufacturer should expect price competition. A differentiated product must demonstrate a practical benefit, such as fewer daily doses, improved tolerability, lower food-effect variability, or a meaningful excipient advantage.

What licensing deals and partnerships are commercially relevant?

The most practical partnership models are API supply agreements, contract development and manufacturing arrangements, regional marketing licenses, and 505(b)(2) co-development agreements.

A formulation owner may license:

• Anagrelide hydrochloride particle engineering.
• A low-dose premix process.
• A lactose-free capsule platform.
• A modified-release delivery system.
• A packaging configuration with improved stability.
• Regulatory dossiers in markets where the originator or generic reference product differs.

Licensing value increases when the technology is supported by comparative dissolution, stability, bioequivalence, manufacturing yield, and patent claims. A simple excipient substitution has limited standalone licensing value.

What is the litigation status for anagrelide hydrochloride?

The principal market risk is generic competition rather than active originator litigation. Standard immediate-release products are unlikely to support substantial current litigation value absent a newly listed formulation or method-of-use patent.

Potential disputes would most likely involve:

• Patent eligibility or validity for a modified-release product.
• Obviousness of an excipient combination.
• Infringement of process claims.
• Regulatory exclusivity for a new indication.
• Trade-secret disputes involving low-dose blending or API processing.
• ANDA certification and labeling issues.

A diligence review should separately assess the FDA Orange Book, USPTO patent status, Federal Court litigation, FDA approval history, and product-specific labeling. Patent expiration should not be inferred from a family’s earliest filing date alone.

Key Takeaways

• Anagrelide hydrochloride is a mature, genericized small-molecule drug used mainly for essential thrombocythemia.
• The standard product is an immediate-release 0.5 mg or 1 mg capsule.
• Common excipients include lactose, povidone, crospovidone, magnesium stearate, gelatin, and colorants.
• The main technical challenge is low-dose content uniformity, not capsule manufacture itself.
• Conventional formulation patents have limited commercial strength unless tied to unexpected performance.
• The strongest opportunities are lactose-free products, vegetarian capsules, improved stability, reliable API supply, and modified-release delivery.
• A standard product is generally suited to an ANDA; a clinically differentiated modified-release product may require a 505(b)(2) application.
• Biosimilar risk is irrelevant because anagrelide is a small molecule.
• Commercial upside is more likely to come from supply reliability and formulation differentiation than from broad patent exclusivity.
• A credible modified-release or tolerability-focused product would have greater licensing value than a routine excipient substitution.

FAQs

Is anagrelide hydrochloride the same as anagrelide?

Anagrelide hydrochloride is the salt form used in drug products, while anagrelide is the active moiety responsible for pharmacologic activity. Labels generally express strength as the equivalent amount of anagrelide.

Can anagrelide capsules be made without lactose?

Yes. Lactose can be replaced with microcrystalline cellulose, mannitol, dibasic calcium phosphate, or another suitable diluent. The replacement must be assessed for blend uniformity, dissolution, stability, and bioequivalence.

Is a vegetarian anagrelide capsule commercially feasible?

Yes. Hypromellose or another non-gelatin capsule shell can be used if the formulation meets manufacturing, dissolution, stability, and regulatory requirements. The commercial premium depends on payer, pharmacy, and institutional demand.

Does anagrelide require a biosimilar development program?

No. Anagrelide is a synthetic small molecule. Generic development generally follows the ANDA pathway rather than the biosimilar pathway.

Could once-daily anagrelide support a new patent?

Potentially, but patent strength would depend on the specific modified-release composition, pharmacokinetic profile, clinical benefit, and non-obviousness. A once-daily claim without supporting technical or clinical differentiation would face substantial validity risk.

References

1. U.S. Food and Drug Administration. (2023). Agrylin (anagrelide hydrochloride) capsules: Prescribing information. FDA.

2. National Library of Medicine. (2024). DailyMed: Anagrelide hydrochloride capsule. U.S. National Library of Medicine.

3. U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs database. FDA.

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

5. U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Generic drug development guidance. FDA.