List of Excipients in Branded Drug GYNAZOLE 1

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Generic Drugs Containing GYNAZOLE 1

Company	Ingredient	NDC	Excipient
Padagis Israel Pharmaceuticals Ltd	butoconazole nitrate	45802-396	EDETATE DISODIUM
Padagis Israel Pharmaceuticals Ltd	butoconazole nitrate	45802-396	GLYCERYL ISOSTEARATE
Padagis Israel Pharmaceuticals Ltd	butoconazole nitrate	45802-396	METHYLPARABEN

What are the Most Frequently-Used Excipients in GYNAZOLE 1?

# Of NDCs	Excipient
1	EDETATE DISODIUM
1	GLYCERYL ISOSTEARATE
1	METHYLPARABEN

Gynazole-1 Excipient Strategy and Commercial Opportunities

Last updated: October 23, 2026

Gynazole-1 is a single-dose vaginal cream containing butoconazole nitrate 2%, equivalent to 100 mg of butoconazole nitrate in a 5-gram prefilled applicator. Its commercial differentiation depends less on the active ingredient than on the cream vehicle, vaginal retention, applicator performance, latex-contraceptive compatibility, and the ability to reproduce the reference product’s formulation and delivery characteristics. The strongest opportunities are authorized-generic supply, formulation-controlled generic entry, improved preservative-free vaginal delivery, and lower-cost single-dose products.

What is Gynazole-1 and how is it formulated?

Gynazole-1 is an intravaginal imidazole antifungal for vulvovaginal candidiasis. The labeled dose is one prefilled 5-gram applicator administered once, preferably at bedtime. Each gram contains 20 mg of butoconazole nitrate in a cream base containing mineral oil, glyceryl monoisostearate, polyoxyl 40 stearate, propylene glycol, and purified water.[1]

Attribute	Gynazole-1 profile
Active ingredient	Butoconazole nitrate
Strength	2% w/w
Dose	5 g once
Active amount per dose	100 mg butoconazole nitrate
Route	Intravaginal
Dosage form	Vaginal cream
Delivery system	Prefilled, disposable applicator
Primary indication	Vulvovaginal candidiasis
Product type	Prescription small-molecule drug
Biologic status	Not applicable
Key formulation issue	Semisolid emulsion with mineral-oil-containing vehicle

The formulation is designed to combine drug dissolution or dispersion, vaginal spreading, local retention, and patient-friendly single-dose administration. Mineral oil also creates a material-compatibility issue: the labeling warns that the cream may damage latex condoms and diaphragms. Patients are instructed to avoid those products during treatment and for 72 hours afterward.[1]

What excipients protect the commercial performance of Gynazole-1?

The excipient system has four functional groups.

Excipient	Likely formulation role	Commercial relevance
Mineral oil	Oil phase, emollient, occlusive vehicle	Supports cream texture and retention but creates latex-compatibility restrictions
Glyceryl monoisostearate	Emulsifier, consistency agent, co-emulsifier	Controls rheology, phase stability, and spreadability
Polyoxyl 40 stearate	Nonionic surfactant and emulsifier	Supports oil-in-water emulsion formation and physical stability
Propylene glycol	Cosolvent, humectant, wetting agent	Influences drug distribution, moisture balance, and irritation potential
Purified water	Continuous aqueous phase	Controls viscosity, dilution, microbial risk, and manufacturing reproducibility

The commercial risk is not limited to matching the ingredient list. A competing product must control particle size or drug distribution, viscosity, yield stress, phase separation, pH, microbial quality, applicator dose delivery, and the amount of cream remaining in the applicator after administration.

For vaginal semisolids, an apparently minor change in emulsifier ratio can alter residence time, leakage, patient perception, and exposure. Substitution of a different mineral oil grade, surfactant, or glycol can affect droplet size and drug release. Those changes may create regulatory comparability issues even when the active ingredient and nominal strength remain identical.

What formulation strategy is best for a Gynazole-1 generic?

The lowest-risk strategy is a close qualitative and quantitative formulation match using the same functional excipient classes, followed by comparative characterization of the finished cream.

Reference-matching strategy

A generic developer should prioritize:

1. Matching the reference product’s excipient identities where possible.
2. Matching the active concentration and total fill weight.
3. Reproducing the emulsion type and rheological profile.
4. Using a functionally equivalent prefilled applicator.
5. Demonstrating equivalent drug distribution and dose delivery.
6. Testing the product in the final container-closure system.

The formulation program should include:

• Appearance and color
• pH
• Viscosity across relevant shear rates
• Yield stress and spreadability
• Globule or droplet-size distribution
• Drug content uniformity
• In vitro release
• Microbial limits
• Preservative effectiveness, if a preservative is used
• Freeze-thaw and accelerated stability
• Applicator fill accuracy
• Residual product in the applicator
• Container-closure compatibility
• Latex compatibility and labeling controls

FDA’s guidance for locally acting gastrointestinal and vaginal products indicates that product performance and local availability can require more than conventional assay and dissolution testing.[2] A vaginal cream developer therefore benefits from a product-specific performance package rather than relying only on pharmacopeial release testing.

Reformulation strategy

A reformulated product could remove mineral oil, replace the surfactant system, or use a bioadhesive aqueous gel. That route creates greater commercial differentiation but also increases regulatory and clinical risk.

Potential advantages include:

• Reduced concern about latex condom and diaphragm damage
• Lower greasy residue
• Improved washout
• Better patient acceptability
• Possible preservative-free positioning
• A delivery system designed for longer vaginal residence

Potential disadvantages include:

• New irritation or sensitization profile
• Different drug release and local exposure
• Greater risk of inadequate therapeutic equivalence
• More complex FDA bridging requirements
• Higher manufacturing-development cost
• New intellectual-property exposure around polymers, bioadhesive systems, or applicators

The most defensible development sequence is a reference-matched generic first, followed by a differentiated reformulation only if the commercial opportunity supports additional development expense.

What FDA regulatory pathway applies to Gynazole-1?

Gynazole-1 is associated with NDA 020649 in FDA drug databases.[3] A conventional generic would generally pursue an abbreviated new drug application under section 505(j) of the Federal Food, Drug, and Cosmetic Act, provided the applicant can satisfy the applicable bioequivalence and product-performance requirements.

The key regulatory question is whether the product can be demonstrated to be pharmaceutically equivalent and bioequivalent to the reference listed drug. For a locally acting vaginal cream, the evidence package may require more than systemic pharmacokinetic comparison because systemic concentrations may not fully characterize local performance.

A product with a materially different vehicle, delivery system, or dosing regimen may fall outside the lowest-risk ANDA strategy. It could require a 505(b)(2) application or additional clinical and local-performance evidence.

Is Gynazole-1 eligible for an authorized generic?

An authorized generic could use the approved NDA pathway and the existing clinical and regulatory record, subject to the commercial rights held by the NDA owner. The opportunity depends on:

• Current ownership or licensing of NDA 020649
• Whether the NDA holder has a manufacturing or distribution partner
• Existing generic competition
• Current product supply
• Wholesale acquisition cost and reimbursement
• Retail pharmacy demand for a single-dose product

An authorized generic would have the lowest regulatory risk but may offer less differentiation and lower margins than an independently developed product.

What patents protect Gynazole-1?

The original butoconazole molecule and early product patents are unlikely to provide meaningful U.S. exclusivity for a mature product first approved in the 1990s. The more relevant protection areas are later-issued patents covering:

• Vaginal cream composition
• Specific excipient ratios
• Single-dose packaging
• Prefilled applicator geometry
• Drug-release characteristics
• Treatment methods
• Manufacturing processes
• Stability improvements

The Orange Book is the controlling public source for patents and regulatory exclusivity associated with an approved drug product.[4] Patent status should be evaluated at the NDA level and not inferred from the age of the active ingredient.

IP category	Likely commercial significance
Original butoconazole compound patents	Low for current U.S. entry if expired
Basic 2% vaginal cream patents	Likely limited if expired
Single-dose formulation patents	Potentially relevant if unexpired and listed
Applicator patents	Relevant to device substitution and packaging
Method-of-use patents	Could affect labeling and Paragraph IV strategy
Manufacturing patents	Can raise CMC and freedom-to-operate issues
Trademark rights	Relevant to branded-generic positioning, not generic approval

A developer should not assume that an unlisted formulation patent is irrelevant. Unlisted patents can still create litigation or freedom-to-operate issues, although they may not support a statutory Orange Book certification in the same way as a listed patent.

When does Gynazole-1 lose exclusivity?

The active ingredient is already mature, and the principal exclusivity question is patent-based rather than new-chemical-entity exclusivity. A drug approved in the 1990s would not retain NCE exclusivity today. Pediatric exclusivity, if ever granted, would also have expired.

The commercial entry date depends on four factors:

1. Whether any Orange Book-listed patent remains enforceable.
2. Whether an ANDA applicant files a Paragraph IV certification.
3. Whether the NDA holder sues within the statutory 45-day period.
4. Whether litigation triggers a 30-month stay or the applicant prevails before that period ends.[5]

A Paragraph IV filing does not itself establish that a generic will launch. It starts a patent-certification and potential litigation process.

Are there Paragraph IV challenges or generic litigation affecting Gynazole-1?

Publicly available information should be checked against the current FDA Orange Book, FDA Paragraph IV database, and PACER court records before relying on a specific launch date. The existence of an ANDA, by itself, does not prove commercial approval or market entry.

For commercial diligence, the relevant litigation questions are:

• Has an ANDA applicant certified Paragraph IV against an Orange Book-listed patent?
• Did the NDA holder file an infringement complaint within 45 days?
• Was a 30-month stay triggered?
• Was the case dismissed, settled, or adjudicated?
• Did the settlement include a licensed entry date?
• Did the agreement contain supply, exclusivity, or no-AG provisions?

No reliable commercial forecast should use a generic launch date without confirming the current Orange Book patent table and federal docket history.

What formulation patents could create a new commercial opportunity?

A reformulated butoconazole product could seek protection around product attributes that matter clinically and commercially.

Preservative-free vaginal cream

A preservative-free formulation may appeal to patients with recurrent irritation or sensitivity. The formulation challenge is microbial control in a water-containing semisolid. Single-dose packaging reduces repeated-container contamination but does not remove manufacturing microbial-control requirements.

Potential protection could cover:

• Preservative-free composition
• Specific emulsifier system
• Water activity
• Packaging and fill process
• Stability profile
• Single-use delivery configuration

Bioadhesive or extended-residence formulation

A mucoadhesive gel or cream could reduce leakage and improve local retention. Candidate excipients include carbomers, cellulose derivatives, polycarbophil, hyaluronic-acid derivatives, and other vaginally tolerated polymers.

The primary risk is that stronger adhesion may increase irritation, alter drug release, or produce unacceptable residue. A successful product would need to show improved residence without compromising tolerability.

Non-mineral-oil vehicle

A non-oily vehicle could remove the latex-compatibility warning. This is commercially attractive because patients may prefer continued use of condoms or diaphragms. The replacement vehicle must maintain drug solubilization, emulsion stability, local tolerability, and shelf life.

Low-mess applicator system

A redesigned applicator could improve dose delivery and reduce leakage. Device claims may protect:

• Nozzle geometry
• Plunger design
• Dose metering
• Tamper evidence
• Applicator material compatibility
• Single-use packaging

Device protection should be assessed alongside drug formulation patents because the commercial value may reside in the complete product system.

How strong is the Gynazole-1 patent estate?

The basic patent estate is likely weaker than that of a recently approved drug because butoconazole and the original product have a long market history. The strongest remaining barriers, if any, are more likely to involve formulation, packaging, device, or method-of-use claims than the active ingredient.

Estate component	Relative strength assessment
Active ingredient	Low, based on product maturity
Original formulation	Low to moderate, depending on surviving claims
Single-dose presentation	Moderate if claims remain enforceable
Prefilled applicator	Moderate, with design-around potential
Excipient-specific claims	Moderate if narrow and technically difficult to avoid
Method of use	Variable; dependent on listed claims and approved labeling
Manufacturing process	Potentially strong if process is difficult to replicate
Trade secret know-how	Potentially meaningful for emulsion manufacture and filling

The most practical barrier for a generic competitor may be CMC execution rather than patent exclusion. Reproducing a stable vaginal emulsion with consistent rheology and accurate applicator filling can take longer than expected, particularly when the product has limited public performance data.

What commercial opportunities exist for Gynazole-1?

Authorized generic or branded generic

This is the lowest-risk commercial opportunity. The product already has a recognized dosage form, a simple one-dose regimen, and an established clinical use. The main constraints are market size, reimbursement, current generic availability, and access to the approved formulation or NDA rights.

Independent ANDA

A formulation-matched generic could compete on price and pharmacy coverage. The value proposition is strongest if the reference product has limited supply, a high price, or inadequate generic competition.

Reformulated prescription product

A non-mineral-oil or bioadhesive product could support premium pricing if it provides a clinically meaningful benefit. Claims should focus on measurable attributes such as improved retention, reduced leakage, or compatibility with latex barrier contraceptives.

Contract manufacturing and licensing

A company with semisolid manufacturing, vaginal-product development, or prefilled-device capabilities could license:

• A formulation platform
• An applicator design
• A manufacturing process
• An ANDA
• An authorized-generic supply arrangement

The most attractive partner would likely be a company with established women’s-health distribution and sterile or nonsterile semisolid filling capability.

Geographic expansion

U.S. approval does not automatically create global approval. Canada, the European Union, the United Kingdom, Australia, and Latin American markets may require different comparability, labeling, device, and local clinical evidence. A formulation platform that avoids mineral oil could have particular value in markets where condom use and nonhormonal contraception are major considerations.

How does Gynazole-1 compare with competing vaginal antifungals?

Product category	Typical regimen	Commercial advantage	Formulation weakness
Butoconazole 2% cream	Single dose	Convenience and established product	Mineral-oil latex warning
Clotrimazole vaginal products	One to seven days, depending on product	Broad retail familiarity	Multiple-dose regimens and variable adherence
Miconazole vaginal products	One to seven days	Strong consumer recognition and OTC access	Oily formulations and leakage concerns
Terconazole vaginal products	One to seven days	Prescription positioning and multiple dosage forms	More complex regimen options
Oral fluconazole	Usually single oral dose	No vaginal application	Systemic exposure, interactions, and contraindications

Gynazole-1’s clearest product advantage is one-dose local treatment. Its clearest product disadvantage is the mineral-oil warning affecting latex condoms and diaphragms. A product that preserves single-dose convenience while removing that restriction would have a direct competitive claim, subject to FDA substantiation.

What revenue exposure and launch scenarios should investors model?

Revenue depends on market access rather than patient population alone. A practical scenario framework is:

Scenario	Product position	Main value driver	Main risk
Low-risk generic	Formulation-matched ANDA	Price and pharmacy access	Rapid price erosion
Authorized generic	NDA-backed equivalent	Faster regulatory execution	Limited differentiation
Premium reformulation	Non-oily or bioadhesive cream	Patient convenience and compatibility	Higher development and approval cost
Device-led product	Improved applicator	Dose delivery and user experience	Device and combination-product complexity
Global platform	Localized multi-market product	Manufacturing scale	Country-specific regulatory requirements

A branded formulation investment is more attractive if the sponsor can demonstrate a product-level advantage over generic cream, not merely a different excipient list. The highest-value claims are likely to involve latex compatibility, improved residence, lower leakage, reduced irritation, or better dose delivery.

Key Takeaways

• Gynazole-1 is a 2% butoconazole nitrate vaginal cream delivered as one 5-gram dose.
• Its core excipient system contains mineral oil, glyceryl monoisostearate, polyoxyl 40 stearate, propylene glycol, and purified water.
• The main formulation-development challenge is reproducing emulsion stability, rheology, local retention, and applicator dose delivery.
• Mineral oil creates a commercial disadvantage because the product can damage latex condoms and diaphragms for up to 72 hours after treatment.
• The most practical near-term opportunity is a formulation-matched generic or authorized generic.
• The strongest differentiated opportunity is a single-dose, non-mineral-oil or bioadhesive formulation with demonstrated patient-use benefits.
• Gynazole-1 has no biosimilar risk because it is a small-molecule drug, not a biologic.
• Patent diligence should focus on current Orange Book listings, formulation claims, applicator patents, method-of-use claims, and Paragraph IV litigation.
• Manufacturing know-how may be a more significant barrier than the expired basic active-ingredient patent estate.
• Commercial forecasts should separate regulatory approval risk, patent timing, pharmacy access, and post-entry generic price erosion.

FAQs

Can Gynazole-1 be reformulated without mineral oil?

Yes, but a replacement vehicle would need to preserve drug release, emulsion stability, vaginal tolerability, shelf life, and dose delivery. A reformulation could support a differentiated 505(b)(2) strategy if it provides a meaningful product advantage.

Does Gynazole-1 have biosimilar competition?

No. Butoconazole nitrate is a small-molecule active ingredient. Potential competitors would be generics, authorized generics, or reformulated products rather than biosimilars.

Is the Gynazole-1 applicator part of the product’s competitive advantage?

Yes. The prefilled single-use applicator supports one-dose convenience, dose accuracy, and product differentiation. Applicator design and fill performance should be evaluated for both patent exposure and regulatory comparability.

Could an OTC company commercialize a Gynazole-1 equivalent?

Potentially, but an OTC switch would require FDA authorization and an appropriate labeling and safety basis. Prescription-to-OTC status cannot be assumed from the product’s established history.

Which excipient change is most likely to create regulatory risk?

Changing the vehicle’s emulsifier or polymer system is likely to create greater risk than changing a minor processing aid because it can alter viscosity, drug release, local exposure, residence time, and irritation.

References

1. DailyMed. (n.d.). Gynazole-1: Butoconazole nitrate vaginal cream, 2% prescribing information. U.S. National Library of Medicine.
2. U.S. Food and Drug Administration. (2019). Draft guidance for industry: Bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA.
3. U.S. Food and Drug Administration. (n.d.). Drugs@FDA: Gynazole-1, NDA 020649.
4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
5. U.S. Food and Drug Administration. (2017). Guidance for industry: 180-day exclusivity: Questions and answers.