List of Excipients in Branded Drug BEYAZ

Beyaz Excipient Strategy and Commercial Opportunities

Last updated: September 8, 2026

Beyaz is a combination oral contraceptive containing drospirenone, ethinyl estradiol, and levomefolate calcium. Its commercial differentiation came from combining a 24-day hormonal regimen with folate supplementation, rather than from a novel excipient system. The strongest opportunities now are generic substitution, lower-cost excipient sourcing, lactose-reduced or lactose-free reformulation, improved tablet robustness, and alternative folate delivery formats.

What is Beyaz and what is its dosage-form architecture?

Beyaz is an oral, immediate-release, film-coated tablet approved by the FDA in 2010. Each active tablet contains:

Component	Amount per active tablet	Functional role
Drospirenone	3 mg	Progestin
Ethinyl estradiol	0.02 mg	Estrogen
Levomefolate calcium	0.451 mg	Folate source equivalent to approximately 0.4 mg folic acid

The marketed pack contains 24 active tablets followed by four inactive tablets. The regimen is intended to provide continuous daily tablet-taking, with the inactive tablets maintaining packaging and adherence continuity rather than delivering pharmacologic activity.

Beyaz uses a conventional immediate-release compressed-tablet platform. The principal formulation challenge is not dissolution of the bulk excipients. It is the uniform distribution of low-dose active ingredients, particularly ethinyl estradiol, drospirenone, and levomefolate calcium, across a high-volume production batch.

What excipients are used in Beyaz tablets?

Public product labeling identifies conventional tablet excipients, including lactose monohydrate, microcrystalline cellulose, pregelatinized starch, magnesium stearate, croscarmellose sodium, hypromellose, talc, titanium dioxide, and colorants such as iron oxide. The precise use and location of each excipient can differ between the active and inactive tablet components and coating system. (Bayer HealthCare Pharmaceuticals, 2010; DailyMed, 2024)

Excipient class	Likely formulation function	Commercial relevance
Lactose monohydrate	Diluent and tablet-mass contributor	Low cost and established supply; creates a lactose-intolerance and labeling consideration
Microcrystalline cellulose	Dry binder and filler	Supports direct compression and tablet hardness
Pregelatinized starch	Binder and disintegrant	Improves compactability and break-up
Croscarmellose sodium	Superdisintegrant	Supports rapid tablet disintegration
Magnesium stearate	Lubricant	Controls ejection force but can delay wetting or dissolution if overused
Hypromellose	Film-coating polymer	Provides mechanical protection and appearance
Talc	Anti-tacking and coating aid	Useful in film coating; subject to supplier-quality controls
Titanium dioxide	Opacifier and whitening agent	Regulatory and market-preference scrutiny in some jurisdictions
Iron oxides	Tablet identification and color	Enables active/inactive tablet differentiation

The formulation is compatible with standard high-speed rotary compression and aqueous or solvent-based film coating. It does not require a modified-release polymer, osmotic system, enteric coating, or specialized delivery device.

How should an excipient strategy address Beyaz’s low-dose actives?

The highest technical risk is content uniformity. The active ingredients are present at low levels relative to the tablet mass, and the product contains multiple pharmacologically distinct compounds. A generic manufacturer should prioritize blend uniformity, segregation control, and validated sampling over excipient novelty.

Content uniformity and segregation

A robust process may use geometric dilution, ordered blending, or pre-blending of low-dose actives with a portion of microcrystalline cellulose or pregelatinized starch. Particle-size distribution and density matching are important because drospirenone, ethinyl estradiol, and levomefolate calcium may segregate differently from the principal fillers.

The formulation should control:

• Active-particle size and surface area
• Bulk and tapped density
• Blend time and lubricant exposure
• Hopper residence time
• Transfer-point segregation
• Tablet weight variation
• Assay and content uniformity across the compression run

A direct-compression process can reduce manufacturing steps, but it may increase segregation risk if the active and excipient particles have materially different flow properties. Wet granulation may improve uniformity and flow but adds moisture, heat, and process complexity.

Disintegration and dissolution

Croscarmellose sodium and pregelatinized starch provide a conventional disintegration system. Excess magnesium stearate or prolonged lubrication can reduce wetting and slow dissolution. A formulation developer should establish a design space linking lubricant concentration, blending time, hardness, friability, disintegration, and dissolution.

The target should be rapid, reproducible immediate release rather than a novel dissolution profile. Any excipient change that materially shifts dissolution could create a bioequivalence risk, particularly because hormonal contraceptive products are administered at low dose and are evaluated against a narrow reference-product profile.

Folate stability

Levomefolate calcium introduces a separate stability burden. Folate compounds can be sensitive to light, oxygen, moisture, and processing conditions. The manufacturing strategy should use:

• Low-moisture excipient grades
• Light-protective packaging
• Controlled oxygen exposure where justified
• Stability-indicating assay methods
• Compatibility studies with colorants and coating systems
• Packaging capable of preserving folate potency through shelf life

The folate component can be a differentiator only if the finished product maintains labeled potency. A low-cost formulation that produces folate degradation creates regulatory and commercial exposure.

What excipient changes create the strongest commercial opportunities?

Lactose-reduced or lactose-free Beyaz alternatives

Lactose is a low-cost, well-understood filler, but a lactose-free presentation could address patient and pharmacy preferences. Candidate replacements include:

• Mannitol
• Dibasic calcium phosphate
• Spray-dried mannitol
• Silicified microcrystalline cellulose
• Crospovidone-containing filler systems
• Coprocessed cellulose-based excipients

A lactose-free product would need to preserve tablet weight, hardness, disintegration, dissolution, content uniformity, and manufacturability. Mannitol may improve mouthfeel but can increase cost. Dibasic calcium phosphate can improve compactability but may complicate compatibility and density matching. Coprocessed excipients can simplify scale-up but often carry higher unit costs and supplier concentration risk.

Reduced titanium dioxide or alternative coating systems

A titanium-dioxide-free coating could support European and selected consumer markets where titanium dioxide faces greater regulatory scrutiny. Alternatives include calcium carbonate, starch-based opacifiers, or reduced-opacity color systems. The key commercial benefit is geographic flexibility, not a new clinical claim.

The main risks are color consistency, light protection, coating weight, and product identification. Active and inactive tablets must remain visually distinguishable to limit dosing errors.

Lower-cost excipient sourcing

The original formulation relies on commodity excipients with multiple qualified suppliers. A generic manufacturer can reduce cost through:

• Dual sourcing of lactose, microcrystalline cellulose, starch, and magnesium stearate
• Use of regional film-coating suppliers
• Supplier qualification based on particle-size distribution rather than compendial compliance alone
• Reduced coating weight
• Improved tablet tooling and compression speed
• Elimination of unnecessary processing steps

Excipient substitution is commercially attractive when it is formulation-neutral. Changes to excipient grade, particle size, or surface treatment can affect dissolution and bioequivalence even when the chemical identity is unchanged.

What regulatory pathway applies to generic Beyaz products?

A conventional generic product would generally be submitted under an abbreviated new drug application, provided the applicant can demonstrate pharmaceutical equivalence and bioequivalence to the reference listed drug. FDA requirements include appropriate active ingredients, strength, dosage form, route of administration, labeling, quality controls, and manufacturing compliance. (U.S. Food and Drug Administration, 2024a)

The principal regulatory issues are:

Issue	Beyaz-specific consideration
Active ingredients	Must include drospirenone, ethinyl estradiol, and levomefolate calcium
Strength	3 mg, 0.02 mg, and 0.451 mg per active tablet
Dosage form	Immediate-release oral tablet
Regimen	24 active tablets and four inactive tablets
Bioequivalence	Hormonal actives require comparative pharmacokinetic evaluation; folate also requires appropriate analytical assessment
Inactive ingredients	Differences may be acceptable if safety, quality, and performance requirements are met
Labeling	Must preserve contraceptive, premenstrual dysphoric disorder, acne, folate, and safety information applicable to the reference product
Packaging	Must preserve folate potency and clearly distinguish active from inactive tablets

A product using a materially different delivery system, a new therapeutic claim, or a substantially altered folate presentation could require a 505(b)(2) pathway rather than a conventional ANDA.

What is the Orange Book and exclusivity status of Beyaz?

Beyaz was approved under NDA 022372 on September 24, 2010. Its original regulatory exclusivity period has expired. The product is therefore commercially relevant primarily as a generic-reference opportunity rather than as an exclusivity-protected innovator product. (U.S. Food and Drug Administration, 2024b)

The original product was associated with patent protection covering the drug combination and related use or formulation claims. Patent and listing status must be evaluated in the current FDA Orange Book and the relevant U.S. patent records because listed patents, delistings, terminal disclaimers, and litigation outcomes can change the launch analysis.

Exclusivity category	Beyaz position
New chemical entity exclusivity	Expired
Three-year clinical-investigation exclusivity	Expired
Pediatric exclusivity	No current commercial barrier identified from the original approval timeline
Orange Book patents	Must be assessed against the current listing and expiration data
Generic pathway	ANDA is the principal pathway for a pharmaceutically equivalent product
Paragraph IV risk	Relevant only if a live listed patent remains that could block or delay approval

A Paragraph IV filing could create litigation exposure if a patent remains listed and the applicant certifies that the patent is invalid, unenforceable, or will not be infringed. If no unexpired listed patent remains, the commercial focus shifts to approval timing, manufacturing readiness, and pharmacy substitution.

What formulation patents and manufacturing barriers matter?

The most defensible intellectual-property positions for a Beyaz-type product would likely relate to:

• Specific ratios of drospirenone, ethinyl estradiol, and folate
• Tablet composition and excipient ranges
• Active-tablet and placebo-tablet packaging configurations
• Folate stabilization systems
• Methods for reducing degradation
• Specific therapeutic uses
• Manufacturing processes that improve low-dose content uniformity

An excipient strategy can create practical barriers even where broad composition patents have expired. A formulation using a particular stabilization system, coating architecture, or manufacturing process may be protected by narrower claims. A competitor can often design around those claims by changing filler grade, granulation method, coating system, or packaging, but each change must still meet bioequivalence and stability requirements.

Manufacturing is therefore a larger barrier than excipient availability. The difficult steps are low-dose blending, uniform compression, folate stability, and reliable 28-day pack assembly.

Which companies are positioned to compete with Beyaz?

Competition is likely to come from three product groups:

1. Generic drospirenone/ethinyl estradiol/levomefolate calcium tablets.
2. Generic drospirenone/ethinyl estradiol products without folate.
3. Alternative oral contraceptives using other progestins, estrogen doses, or dosing schedules.

The closest products compete on pharmacy substitution and price. Products without folate may have lower manufacturing cost, while Beyaz-equivalent products retain a potential adherence and prenatal-folate positioning. The commercial advantage of folate is strongest among patients and prescribers who value preconception folate exposure, but it is weakened when payers treat the product as a premium version of a low-cost oral contraceptive.

How large is the revenue opportunity?

The opportunity is a mature generic-market opportunity rather than a high-growth branded opportunity. Revenue depends on:

• Whether the innovator product remains actively marketed
• The number of approved generic suppliers
• Reimbursement and formulary placement
• Pharmacy substitution
• Wholesale acquisition price
• The cost premium for the folate-containing combination
• Availability of competing drospirenone products

A manufacturer can target three segments:

Segment	Product strategy	Commercial logic
Value generic	Conventional excipient system and low manufacturing cost	Competes for pharmacy and payer volume
Differentiated generic	Lactose-free, titanium-dioxide-free, or improved stability formulation	Supports selective pricing and market access
Branded alternative	Patient-friendly packaging, adherence support, or alternative folate delivery	Requires stronger marketing and may face reimbursement limits

Because the active ingredients are established and the original exclusivity has expired, sustainable margins will depend more on supply reliability and cost control than on patent exclusivity.

How does Beyaz compare with other drospirenone oral contraceptives?

Product type	Drospirenone	Ethinyl estradiol	Folate	Primary differentiation
Beyaz-type product	3 mg	0.02 mg	Yes	Folate-containing 24/4 regimen
Yaz-type product	3 mg	0.02 mg	No	Lower-cost hormonal combination
Yasmin-type product	3 mg	0.03 mg	No	Higher estrogen dose and 21/7-style regimen
Progestin-only products	Varies	None	Usually no	Estrogen-free contraception

Beyaz’s technical distinction is the addition of levomefolate calcium. Its excipient platform is otherwise conventional. A competing product can therefore differentiate through cost, folate stability, packaging, or patient tolerability rather than through a fundamentally different delivery technology.

What generic launch risks exist?

The principal launch risks are:

• Failure to achieve active-content uniformity
• Folate degradation during shelf life
• Dissolution shifts caused by lubricant or filler changes
• Inadequate segregation control during high-speed compression
• Tablet appearance or packaging errors between active and inactive tablets
• Regulatory deficiencies involving comparative labeling
• Patent litigation if a live Orange Book listing remains
• Supply interruption for qualified low-dose active ingredients
• Price erosion after multiple generic entries
• Safety-related market restrictions associated with drospirenone-containing contraceptives

The most attractive development program is usually a formulation-conservative generic with targeted improvements in excipient sourcing and folate stability. A broad excipient redesign may add regulatory and bioequivalence risk without producing a proportionate commercial benefit.

Key Takeaways

• Beyaz contains drospirenone, ethinyl estradiol, and levomefolate calcium in a 24-active/4-inactive tablet regimen.
• Its excipient system is conventional and supports immediate release, high-speed compression, and film coating.
• Content uniformity and folate stability are the main technical priorities.
• Lactose-free, titanium-dioxide-free, and improved-stability versions offer the clearest formulation opportunities.
• Original FDA exclusivity has expired, making generic development the main commercial pathway.
• A current Orange Book and patent-record review is required before any Paragraph IV or launch-timing decision.
• Manufacturing control, packaging quality, and cost leadership are more important than novel excipient claims in a mature generic market.

FAQs About Beyaz Excipient and Commercial Strategy

Can Beyaz be reformulated without lactose?

Yes. Lactose can be replaced with mannitol, dibasic calcium phosphate, spray-dried excipients, or coprocessed cellulose systems, but the replacement must preserve content uniformity, tablet strength, disintegration, dissolution, and stability.

Is levomefolate calcium a patentable commercial differentiator?

It can support composition, formulation, stabilization, or use claims, but the commercial value depends on the status of live patent claims and the ability of competitors to market drospirenone/ethinyl estradiol products without folate.

What is the most important excipient for Beyaz manufacturing?

No single excipient controls performance. Microcrystalline cellulose and pregelatinized starch are central to compression and binding, while croscarmellose sodium supports disintegration. Magnesium stearate requires tight control because over-lubrication can affect dissolution.

Does a generic Beyaz product need to use the same inactive ingredients?

No. FDA-approved generics may use different inactive ingredients if the formulation meets applicable safety, quality, performance, labeling, and bioequivalence requirements.

Is Beyaz a biosimilar opportunity?

No. Beyaz is a chemically synthesized small-molecule oral tablet. The relevant regulatory route is a generic ANDA or, for certain reformulations or new claims, a 505(b)(2) application. Biosimilar rules do not apply.

References

1. Bayer HealthCare Pharmaceuticals. (2010). Beyaz (drospirenone, ethinyl estradiol, and levomefolate calcium) tablets: Prescribing information.

2. DailyMed. (2024). Beyaz: Drospirenone, ethinyl estradiol, and levomefolate calcium tablet, film coated. U.S. National Library of Medicine.

3. U.S. Food and Drug Administration. (2024a). Orange Book: Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.

4. U.S. Food and Drug Administration. (2024b). Drugs@FDA: Beyaz, NDA 022372. Center for Drug Evaluation and Research.

5. U.S. Food and Drug Administration. (2023). Guidance for industry: ANDAs for certain highly purified synthetic peptides and other complex drug substances. Center for Drug Evaluation and Research.