List of Excipients in Branded Drug GLYBURIDE

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
TEVA Pharmaceuticals USA Inc	GLYBURIDE	glyburide	0093-9477	ANHYDROUS DIBASIC CALCIUM PHOSPHATE
TEVA Pharmaceuticals USA Inc	GLYBURIDE	glyburide	0093-9477	CELLULOSE, MICROCRYSTALLINE
TEVA Pharmaceuticals USA Inc	GLYBURIDE	glyburide	0093-9477	MAGNESIUM PALMITOSTEARATE
TEVA Pharmaceuticals USA Inc	GLYBURIDE	glyburide	0093-9477	SODIUM ALGINATE

Generic Drugs Containing GLYBURIDE

Company	Ingredient	NDC	Excipient
Teva Pharmaceuticals USA Inc	glyburide	0093-8034	CELLULOSE, MICROCRYSTALLINE
Teva Pharmaceuticals USA Inc	glyburide	0093-8034	MAGNESIUM STEARATE
Teva Pharmaceuticals USA Inc	glyburide	0093-8034	SILICON DIOXIDE
Teva Pharmaceuticals USA Inc	glyburide	0093-8034	SODIUM STARCH GLYCOLATE TYPE A POTATO

What are the Most Frequently-Used Excipients in GLYBURIDE?

# Of NDCs	Excipient
15	ALUMINUM OXIDE
2	CALCIUM CARBONATE
2	CALCIUM PHOSPHATE, DIBASIC, ANHYDROUS
2	CALCIUM PHOSPHATE, DIBASIC, DIHYDRATE

Glyburide Excipient Strategy and Commercial Opportunities

Last updated: August 4, 2026

Glyburide, also known as glibenclamide, is an established sulfonylurea with limited molecule-level exclusivity and a low-cost generic market. The main commercial opportunity is not a new chemical entity or conventional generic tablet. It is a differentiated oral formulation that improves dissolution, reduces food-effect variability, supports dose flexibility, or targets under-served uses such as gestational diabetes and neonatal diabetes. The central formulation problem is glyburide’s very low aqueous solubility and narrow therapeutic margin, which make excipient selection directly relevant to exposure, hypoglycemia risk, and regulatory comparability.

What is the current FDA status of glyburide?

Glyburide is an FDA-approved oral antidiabetic drug indicated as an adjunct to diet and exercise for adults with type 2 diabetes. It is marketed in conventional and micronized tablet forms, although branded availability has declined and the market is primarily generic.

Product type	Typical strengths	Formulation position
Conventional glyburide tablets	1.25 mg, 2.5 mg, 5 mg	Immediate-release, non-micronized or conventional particle-size product
Micronized glyburide tablets	1.5 mg, 3 mg, 6 mg	Smaller particle size with higher dissolution and dose conversion considerations
Combination products	Usually metformin plus glyburide	Fixed-dose combination; formulation and bioequivalence complexity is higher
Investigational modified formulations	Variable	Nanoparticles, solid dispersions, lipid systems, and other solubility-enhancing platforms

FDA labeling identifies glyburide as a sulfonylurea that stimulates pancreatic insulin secretion. The label warns about severe hypoglycemia, particularly in elderly, debilitated, malnourished, or renally or hepatically impaired patients (FDA, 2019a; FDA, 2023).

The FDA-approved glyburide products are immediate-release oral products. There is no established FDA commercial category for an extended-release glyburide product comparable to extended-release metformin.

What excipient problems does glyburide create?

Glyburide is a poorly water-soluble compound with dissolution-limited oral absorption. Its low solubility creates several formulation constraints:

1. Tablet disintegration alone may not provide consistent dissolution.
2. Food, gastric conditions, particle size, and excipient wetting can affect exposure.
3. Excessive solubility enhancement can increase peak concentrations and hypoglycemia risk.
4. Changes in excipient composition can alter bioequivalence even when the dose remains unchanged.
5. Glyburide’s narrow safety margin increases the commercial value of exposure consistency.

Micronized glyburide demonstrates the commercial importance of particle engineering. Micronization increases surface area and can improve dissolution, but it also creates a dose-conversion issue. Conventional and micronized products are not interchangeable on a milligram-for-milligram basis. FDA labeling identifies 1.25 mg, 2.5 mg, and 5 mg conventional tablets and 1.5 mg, 3 mg, and 6 mg micronized tablets as different strength systems (FDA, 2019a; FDA, 2019b).

Which excipients are most relevant for glyburide tablets?

Wetting agents and surfactants

Surfactants can improve wetting and reduce interfacial resistance between glyburide particles and gastrointestinal fluid. Candidates include sodium lauryl sulfate, polysorbates, poloxamers, and certain nonionic surfactants.

Their commercial value is highest in low-dose immediate-release tablets where a small excipient change can materially improve dissolution. The principal risks are gastrointestinal tolerability, tablet performance, oxidation or peroxide impurities in some excipient grades, and an excessive increase in early exposure.

Disintegrants

Crospovidone, croscarmellose sodium, and sodium starch glycolate can accelerate tablet breakup. These excipients are useful when the formulation bottleneck is tablet disintegration rather than intrinsic drug dissolution.

Disintegrants alone are unlikely to solve glyburide’s solubility problem. They are better used with particle-size control, wetting agents, or a porous carrier.

Hydrophilic binders and porous carriers

Povidone, copovidone, hypromellose, microcrystalline cellulose, and colloidal silicon dioxide can support dispersion of glyburide and improve powder handling. Porous carriers can increase surface exposure and reduce agglomeration.

These systems must be controlled carefully because excessive binder levels can slow disintegration and produce a formulation that is mechanically robust but dissolution-limited.

Solubilizers and complexing agents

Cyclodextrins, especially hydroxypropyl-beta-cyclodextrin and sulfobutyl ether-beta-cyclodextrin, may improve apparent solubility through inclusion complexation. They can be useful in liquid, sublingual, or rapidly dissolving products, but their cost and required loading may be unsuitable for a low-price generic tablet.

Cyclodextrin systems also introduce new questions involving complex stability, release kinetics, residual moisture, and scale-up. Their strongest commercial use case is a differentiated product rather than a conventional ANDA.

Lipid excipients

Medium-chain triglycerides, glycerides, lipid surfactants, and self-emulsifying drug delivery systems may improve glyburide dissolution and oral absorption. These systems are more promising for softgels, liquid-filled capsules, or multiparticulate products than for standard compressed tablets.

The major development risks are food-effect amplification, capsule compatibility, oxidative stability, and difficulty establishing a robust in vitro-in vivo relationship.

Polymeric solid-dispersion excipients

Povidone, copovidone, Soluplus-type polymers, hypromellose acetate succinate, and related polymers can stabilize amorphous glyburide and improve apparent solubility.

Solid dispersions create a stronger formulation patent position than routine tablet excipient substitution. They also create higher technical risk. Recrystallization, moisture sensitivity, residual solvent, spray-drying control, and long-term physical stability must be addressed before the product can support a premium commercial claim.

What formulation patents could protect a glyburide product?

The most defensible formulation patent claims would focus on a technically defined delivery system rather than a list of routine excipients.

Potential claim categories

Claim category	Commercial objective	Relative patent value
Micronized glyburide with defined particle-size distribution	Faster dissolution and dose consistency	Moderate if narrowly characterized
Amorphous glyburide dispersion	Higher apparent solubility	High if stability and clinical benefit are demonstrated
Nanocrystalline glyburide	Improved dissolution and reduced variability	Moderate to high, depending on manufacturing claims
Lipid-based formulation	Enhanced dissolution and absorption	Moderate
Cyclodextrin complex	Increased aqueous solubility	Moderate, with high formulation-loading risk
Multiparticulate or orally disintegrating product	Dose flexibility and administration convenience	Moderate
Excipient-specific composition	Reproducible dissolution or reduced food effect	Low to moderate unless linked to measurable performance
Manufacturing process	Controlled particle engineering or amorphous stabilization	Moderate to high

A patent that claims “glyburide plus a conventional disintegrant” would face substantial obviousness and enablement pressure. Stronger protection would define particle-size limits, solid-state properties, dissolution thresholds, impurity limits, process parameters, and pharmacokinetic performance.

How strong is the glyburide patent estate?

Glyburide’s molecule-level patent estate is commercially exhausted. The active ingredient has been used for decades, and conventional glyburide products are generic. The practical patent opportunity is therefore formulation, manufacturing process, delivery system, or method of use.

Exclusivity category	Current strategic value
Original compound patent	Expired
Conventional tablet formulation	Generally expired or unavailable as a meaningful barrier
Micronized formulation	Historical differentiation; broad protection is unlikely to block current generic competition
Method-of-use patents for type 2 diabetes	Weak commercial blocking position because the use is established
Pregnancy or gestational-diabetes use	Potentially relevant only for narrow, legally and clinically supportable claims
Solid dispersion or nanocarrier	Highest remaining formulation opportunity
Manufacturing process	Useful as a process moat, but difficult to enforce against undisclosed generic manufacturing
Trade secrets	Relevant for particle engineering, coating, scale-up, and quality control

The relevant patent strategy is a layered estate: composition claims for the formulation, process claims for manufacture, method claims tied to a defined clinical benefit, and device or packaging claims where appropriate.

What is the Orange Book status of glyburide?

Conventional glyburide and micronized glyburide are generic prescription products listed in FDA drug databases and associated labeling. Glyburide is not comparable to a recently approved branded medicine with a large Orange Book patent-and-exclusivity barrier.

The commercial implication is direct:

• A new glyburide product would normally face an ANDA-heavy competitive environment.
• A formulation with a new clinical benefit may require a 505(b)(2) strategy rather than a simple ANDA.
• Orange Book-listed patent protection would need to be evaluated product by product.
• A sponsor cannot assume that a formulation patent automatically creates meaningful market exclusivity.
• Any listed patent must be assessed for scope, expiry, enforceability, and whether generic applicants can design around it.

A 505(b)(2) pathway may be more appropriate for a reformulated glyburide product that relies partly on published literature or FDA findings for glyburide but introduces a new dosage form, route, formulation, or dosing regimen (FDA, 2023).

When does glyburide lose exclusivity?

Glyburide lost meaningful compound and conventional-product exclusivity many years ago. Current competition is primarily from generic manufacturers. The relevant exclusivity date for a new entrant would depend on the applicant’s own regulatory pathway and any newly granted formulation patents or regulatory exclusivities.

Exclusivity issue	Glyburide position
New chemical entity exclusivity	Not applicable
Orphan-drug exclusivity	Not applicable to conventional type 2 diabetes use
Pediatric exclusivity	No established commercial barrier for standard glyburide
New formulation exclusivity	Possible only for a qualifying new product and regulatory pathway
Three-year 505(b)(2) exclusivity	Potentially available for certain new clinical investigations supporting a change
Five-year NCE exclusivity	Not available for glyburide
Patent term extension	No practical relevance to the old molecule

A reformulation sponsor should model commercial protection around formulation patents and any applicable 505(b)(2) exclusivity, not around the glyburide active ingredient.

Are there Paragraph IV challenges involving glyburide?

Paragraph IV litigation is not a major current commercial feature of conventional glyburide. The drug has been generic for decades, and the main market does not depend on a newly introduced branded glyburide product.

For a new reformulated product, Paragraph IV risk would arise if:

1. The sponsor listed eligible formulation or method patents in the Orange Book.
2. A generic applicant submitted an ANDA referencing that product.
3. The ANDA included a Paragraph IV certification against one or more listed patents.

A formulation sponsor should expect challenges to narrow claims covering excipient ratios, particle-size ranges, dissolution windows, or manufacturing parameters. Broad claims are more vulnerable to invalidity arguments based on prior glyburide micronization, conventional solubility enhancement, and known BCS formulation techniques.

What method-of-use opportunities exist for glyburide?

Gestational diabetes

Glyburide has been studied and used in gestational diabetes, but its positioning is clinically sensitive. Studies and professional guidance have raised concerns regarding neonatal hypoglycemia, macrosomia, treatment failure, and placental transfer. The American College of Obstetricians and Gynecologists generally places insulin as the preferred pharmacologic treatment when medication is required (American College of Obstetricians and Gynecologists, 2018).

A commercial product targeting gestational diabetes would need a clear clinical rationale, pregnancy-specific safety evidence, and a carefully controlled exposure profile. A reduced-variability formulation could be more valuable than a high-exposure formulation.

Neonatal diabetes and hyperinsulinemic disorders

Sulfonylureas can have an important role in selected monogenic diabetes cases, especially certain KCNJ11- and ABCC8-related forms. These uses are generally specialist-driven and may require dose escalation, tablet manipulation, or administration to infants and children (International Society for Pediatric and Adolescent Diabetes, 2022).

The opportunity is primarily dosage-form and administration related:

• liquid or dispersible formulations;
• low-dose multiparticulates;
• pharmacy-compounded alternatives with improved stability;
• age-appropriate dosing devices;
• products that reduce crushing and dose-measurement errors.

A method-of-use patent would need to be narrowly tied to a defined genotype, dosing regimen, or clinical outcome. A broad claim covering glyburide treatment of diabetes would have limited defensibility.

What commercial opportunities exist for glyburide excipients?

1. Pediatric and neonatal dosage forms

This is the clearest differentiated-product opportunity. Conventional tablets are poorly suited to infants and young children. A stable oral suspension, dispersible tablet, mini-tablet, or multiparticulate product could address dosing accuracy and administration.

The development challenge is that glyburide is potent, so small dose errors can have clinical consequences. Dose uniformity, content uniformity across a bottle, syringe compatibility, preservative selection, and in-use stability are central specifications.

2. Low-food-effect formulations

A formulation that reduces dependence on meal timing could create clinical value, but it would require pharmacokinetic and clinical evidence. Lipid systems may worsen food effects if they rely on fed-state digestion. Hydrophilic dispersions and controlled wetting may be more suitable for a low-food-effect claim.

3. Micronized or nanocrystalline products

A modern particle-engineered formulation could improve dissolution without requiring high excipient loads. Commercial protection would be stronger if the sponsor could show reduced interpatient variability, less food dependence, or a lower hypoglycemia rate at equivalent glycemic control.

4. Fixed-dose combination products

Glyburide-metformin combinations have existed, but the category remains technically demanding. Glyburide and metformin have different dose, solubility, and release requirements. A differentiated combination could use bilayer tablets, separate multiparticulates, or protective coatings.

The market opportunity is constrained by competition from newer agents and the availability of generic metformin combinations.

5. Excipient and platform licensing

The most realistic licensing opportunity is a platform owner with a validated solubility-enhancement technology. Potential counterparties include generic manufacturers, specialty pharmaceutical companies, and developers of pediatric diabetes products.

A licensable package would need more than laboratory dissolution data. It should include scalable manufacturing, solid-state characterization, stability data, pharmacokinetic results, and a credible patent family.

How does glyburide compare with newer diabetes drugs?

Glyburide competes primarily on cost, not on cardiovascular, renal, weight, or hypoglycemia advantages.

Attribute	Glyburide	Metformin	DPP-4 inhibitors	SGLT2 inhibitors	GLP-1 receptor agonists
Cost position	Low	Low	Higher	Higher	Higher
Hypoglycemia risk	Relatively high	Low when used alone	Low	Low	Low
Weight effect	Gain risk	Neutral or modest loss	Neutral	Loss	Loss
Solubility/formulation opportunity	High	Moderate	Moderate	Moderate	High, especially injectable/oral delivery
Generic competition	Extensive	Extensive	Increasing	Increasing	More limited historically
Differentiation potential for glyburide	Formulation and dosing	Combination and tolerability	Convenience	Organ protection and adherence	Delivery and weight outcomes

The commercial case for glyburide must therefore be based on access, dosing convenience, pediatric suitability, or a measurable safety improvement. A standard excipient reformulation without clinical differentiation is unlikely to command durable pricing power.

What manufacturing and IP barriers matter most?

The main manufacturing barriers are process control rather than raw-material scarcity.

Critical controls include:

• glyburide particle-size distribution;
• polymorph and amorphous content;
• wetting-agent uniformity;
• blend segregation at low drug loading;
• dissolution across physiologic pH;
• moisture uptake and recrystallization;
• content uniformity;
• tablet hardness and disintegration;
• impurity formation during granulation or drying;
• scale-up reproducibility.

For an amorphous dispersion, the key barrier is maintaining supersaturation without recrystallization. For a nanocrystal product, the barrier is controlling particle growth, residual stabilizer, milling contamination, and long-term physical stability. For a liquid product, the barrier is maintaining dose uniformity and chemical stability after opening.

A trade-secret process can complement patents, but it does not replace composition claims. Competitors may reproduce a performance profile through a different process unless the formulation itself is protected.

Which companies are positioned to challenge or compete with a glyburide reformulation?

The competitive field would include:

• established generic manufacturers with glyburide ANDA capability;
• manufacturers of micronized or specialty oral products;
• companies with 505(b)(2) reformulation expertise;
• contract development and manufacturing organizations with spray-drying, nanomilling, or lipid-formulation platforms;
• diabetes-focused specialty companies targeting pediatric or rare genetic diabetes.

The highest competitive risk would come from a generic manufacturer that can reproduce dissolution and pharmacokinetics through routine formulation changes. The strongest defense is a formulation that combines a difficult-to-copy process with clinically demonstrated performance and narrow, well-supported patent claims.

What revenue exposure does glyburide create?

Glyburide-specific revenue data are generally not disclosed by diversified pharmaceutical companies. The product is a mature generic, so overall market revenue is structurally lower than that of branded diabetes therapies.

A commercial model should use scenario analysis rather than historical brand revenue:

Scenario	Product profile	Revenue potential
Commodity generic	Conventional tablet	Low margin, high price competition
Premium generic	Improved dissolution or dose flexibility	Moderate, dependent on payer acceptance
Specialty pediatric product	Liquid, dispersible, or mini-tablet	Higher unit economics but smaller volume
505(b)(2) reformulation	Clinical differentiation and new labeling	Highest potential pricing, higher development cost
Combination product	Glyburide plus metformin	Moderate, with strong generic competition

The most attractive risk-adjusted opportunity is a specialty dosage form with a defined patient population and limited direct competition. A broad adult type 2 diabetes product would face stronger substitution from metformin, newer branded agents, and low-cost generic sulfonylureas.

Key Takeaways

• Glyburide’s active-ingredient exclusivity is exhausted; formulation and process IP are the relevant protection strategies.
• The principal technical problem is poor aqueous solubility and dissolution-limited exposure.
• Micronization is established, but a new product needs a clinical or practical advantage beyond smaller particles.
• The strongest excipient opportunities include amorphous solid dispersions, nanocrystals, lipid systems, cyclodextrin complexes, and pediatric liquid or dispersible products.
• Conventional excipient substitution is unlikely to support durable premium pricing or strong patent protection.
• A 505(b)(2) pathway may be more suitable than an ANDA for a clinically differentiated reformulation.
• The best commercial targets are pediatric dosing, neonatal or monogenic diabetes, reduced variability, and administration convenience.
• Glyburide’s hypoglycemia risk makes exposure control more valuable than maximum solubility.
• Paragraph IV litigation is not a major current issue for standard glyburide, but any new Orange Book-listed formulation patents would be exposed to generic challenge.
• Manufacturing know-how in particle engineering, solid-state stabilization, and content uniformity can provide a meaningful but incomplete competitive barrier.

FAQs

Can glyburide be formulated as an oral suspension?

Yes. An oral suspension is technically feasible, but the formulation must control particle settling, redispersibility, dose uniformity, chemical stability, and syringe delivery. Because glyburide is potent, suspension homogeneity is a critical quality attribute.

Is micronized glyburide interchangeable with conventional glyburide?

No. Micronized and conventional glyburide products use different strength systems and should not be treated as milligram-for-milligram interchangeable without product-specific regulatory and clinical support.

Which excipient is best for increasing glyburide solubility?

No single excipient is universally superior. Surfactants may improve wetting, polymers may stabilize amorphous drug, cyclodextrins may increase apparent solubility, and lipid systems may improve dissolution in the gastrointestinal tract. The choice depends on the dosage form and the target pharmacokinetic profile.

Could a glyburide formulation qualify for new regulatory exclusivity?

Potentially. A reformulated product may qualify for certain 505(b)(2) protections if it contains a meaningful change supported by new clinical investigations. The exclusivity would attach to the approved product or change, not to glyburide as an active ingredient.

Does glyburide have a biosimilar risk?

No. Glyburide is a small-molecule drug, so the relevant competitors are generic drug applicants, not biosimilar manufacturers. Biosimilar pathways apply to biologic products.

References

1. American College of Obstetricians and Gynecologists. (2018). ACOG practice bulletin no. 190: Gestational diabetes mellitus. Obstetrics & Gynecology, 131(2), e49-e64.

2. Food and Drug Administration. (2019a). Glyburide tablets, USP prescribing information. U.S. Department of Health and Human Services.

3. Food and Drug Administration. (2019b). Micronized glyburide tablets prescribing information. U.S. Department of Health and Human Services.

4. Food and Drug Administration. (2023). Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

5. International Society for Pediatric and Adolescent Diabetes. (2022). ISPAD clinical practice consensus guidelines: The diagnosis and management of monogenic diabetes in children and adolescents. Wiley.

6. U.S. National Library of Medicine. (2024). DailyMed: Glyburide drug labels. National Institutes of Health.