List of Excipients in Branded Drug REPAGLINIDE

Generic Drugs Containing REPAGLINIDE

Company	Ingredient	NDC	Excipient
Padagis US LLC	repaglinide	0574-0240	ANHYDROUS DIBASIC CALCIUM PHOSPHATE
Padagis US LLC	repaglinide	0574-0240	CELLULOSE, MICROCRYSTALLINE
Padagis US LLC	repaglinide	0574-0240	GLYCERIN
Padagis US LLC	repaglinide	0574-0240	MAGNESIUM STEARATE
Padagis US LLC	repaglinide	0574-0240	MEGLUMINE
Padagis US LLC	repaglinide	0574-0240	POLACRILIN POTASSIUM

What are the Most Frequently-Used Excipients in REPAGLINIDE?

# Of NDCs	Excipient
19	ANHYDROUS DIBASIC CALCIUM PHOSPHATE
4	BUTYLATED HYDROXYANISOLE
2	CALCIUM PHOSPHATE, DIBASIC, ANHYDROUS
22	CELLULOSE, MICROCRYSTALLINE
1	CROSCARMELLOSE SODIUM
1	DIBASIC CALCIUM PHOSPHATE DIHYDRATE

Repaglinide Excipient Strategy and Commercial Opportunities

Last updated: August 2, 2026

Repaglinide is a mature, immediate-release meglitinide with limited compound-level exclusivity and substantial generic competition. The strongest commercial opportunities are formulation-led: improved dissolution, lower-dose accuracy, orally disintegrating or dispersible tablets, fixed-dose combinations, and differentiated packaging for meal-linked dosing. Excipient selection must address repaglinide’s low aqueous solubility, dose-dependent exposure, rapid onset requirement, and sensitivity to food and drug interactions.

What is repaglinide and how is it administered?

Repaglinide is an oral insulin secretagogue used to improve glycemic control in adults with type 2 diabetes. It stimulates pancreatic beta-cell insulin release and is taken before meals. U.S. labeling provides 0.5 mg, 1 mg, and 2 mg tablet strengths, with dosing adjusted according to glycemic response and meal patterns (FDA, 2023a).

Repaglinide has several formulation characteristics that influence excipient strategy:

Attribute	Formulation relevance
Therapeutic class	Meglitinide insulin secretagogue
Dosage form	Immediate-release oral tablet
Strengths	0.5 mg, 1 mg, 2 mg
Dosing pattern	Before meals; dose may be omitted if a meal is skipped
Solubility	Low water solubility, creating dissolution risk
Permeability	High permeability is generally reported
Absorption	Rapid gastrointestinal absorption
Metabolism	Primarily CYP2C8 and CYP3A4 pathways
Protein binding	High plasma protein binding
Food effect	Food can alter exposure and timing
Commercial status	Mature small-molecule generic market

Repaglinide is commonly characterized as a poorly soluble, highly permeable compound. That profile places dissolution and wetting at the center of product performance. The drug’s low dose also creates content-uniformity and blend-segregation risks, particularly in 0.5 mg tablets.

What excipient strategy is appropriate for repaglinide immediate-release tablets?

The base strategy should prioritize rapid wetting, reproducible disintegration, content uniformity, and low manufacturing complexity. A conventional direct-compression or dry-granulation platform is generally commercially attractive because the drug is administered in low doses and does not require sustained release for its primary therapeutic use.

Recommended excipient functions

Formulation function	Candidate excipient classes	Commercial rationale
Dilution and tablet mass	Microcrystalline cellulose, lactose, mannitol, dibasic calcium phosphate	Supports dose uniformity and tablet size
Disintegration	Crospovidone, croscarmellose sodium, sodium starch glycolate	Promotes rapid tablet breakup
Wetting and dissolution	Sodium lauryl sulfate, poloxamers, surfactant-enabled polymer systems	Improves contact between particles and dissolution medium
Binder	Povidone, copovidone, low-viscosity hydroxypropyl cellulose	Controls granule strength and tablet robustness
Lubrication	Magnesium stearate, sodium stearyl fumarate	Reduces ejection force; excessive use can slow dissolution
Glidant	Colloidal silicon dioxide	Improves flow in low-dose blends
Taste masking	Film coating, polymeric barrier coating, ion-exchange or lipid-based systems	Relevant for orally disintegrating or chewable products
Solubility enhancement	Cyclodextrins, amorphous solid dispersion polymers, lipid or surfactant systems	Supports differentiated products where standard tablets are insufficient

The formulation should avoid over-lubrication. Magnesium stearate can create hydrophobic particle surfaces and delay wetting when used at excessive levels or mixed for too long. This risk is more material for a low-solubility drug because disintegration alone does not guarantee rapid dissolution.

For conventional tablets, microcrystalline cellulose combined with a superdisintegrant is a practical starting point. Mannitol is more relevant where mouthfeel, rapid dissolution, or an orally disintegrating format is targeted. Dibasic calcium phosphate can improve compactability but may require careful compatibility and dissolution testing because insoluble inorganic fillers can alter tablet porosity and drug release.

What formulation challenges does repaglinide create?

Repaglinide presents four main development challenges.

Low aqueous solubility

Poor solubility can limit dissolution after rapid tablet breakup. A product that passes disintegration testing may still show slow or variable drug release. Developers should establish a dissolution method that discriminates between formulations rather than relying only on compendial disintegration.

Useful development tools include:

• Particle-size reduction or controlled micronization
• Surfactant-assisted wetting
• Amorphous solid dispersion screening
• Cyclodextrin complexation
• Co-precipitation or solvent-based dispersion
• Porous carrier systems
• Lipid-based self-emulsifying systems

For a low-cost generic, particle engineering and superdisintegrant optimization are more commercially realistic than complex lipid systems. For a premium reformulation, amorphous dispersions or enabling excipients may create stronger differentiation, but they increase process, stability, and regulatory burden.

Very low dose

The 0.5 mg strength creates a high dilution ratio between active ingredient and excipients. Blend uniformity becomes a critical quality attribute. Risk controls include geometric dilution, ordered mixing, carrier-based premixes, controlled particle-size distribution, and validated sampling plans.

A formulation with a narrow particle-size distribution may be more valuable than one with the lowest nominal excipient cost. Segregation during transfer, hopper storage, and compression can produce out-of-specification assay or content-uniformity results.

Rapid, meal-linked dosing

Repaglinide is taken shortly before meals. The product therefore benefits from rapid disintegration and predictable dissolution rather than prolonged release. A sustained-release product could conflict with the clinical use pattern unless it targets a different dosing concept and establishes a new exposure profile.

The label also warns about hypoglycemia and contraindicates repaglinide with gemfibrozil. CYP3A4 and CYP2C8 interactions are relevant to clinical use, but excipients generally do not solve these metabolic interaction risks (FDA, 2023a).

Taste and mouthfeel

Taste is not a major barrier for standard swallowed tablets. It becomes important for orally disintegrating, chewable, sublingual, or dispersible formats. Repaglinide’s low dose makes taste masking technically feasible because the total active load is small. Film coating, mannitol-based matrices, polymeric taste barriers, and lipid coating can support these formats.

What repaglinide formulations are protected or commercially differentiated?

The original immediate-release tablet concept is mature. The commercial value now lies in product attributes that improve use, manufacturing, or access rather than in the basic active ingredient.

Conventional immediate-release tablets

This is the lowest-risk route. Differentiation can come from:

• Faster dissolution
• Smaller tablet size
• Improved 0.5 mg content uniformity
• Scored tablets
• Color-coded strengths
• Moisture-protective packaging
• Lower-cost manufacturing
• Reliable supply of all three strengths

A standard generic tablet has limited pricing power. The opportunity is operational efficiency and share capture, not premium positioning.

Orally disintegrating tablets

An orally disintegrating tablet could target patients who have difficulty swallowing or who need a portable pre-meal product. Mannitol, crospovidone, low-substituted hydroxypropyl cellulose, and taste-masking polymers are plausible excipient components.

The main development risks are friability, moisture sensitivity, packaging cost, and the need to demonstrate rapid in vitro performance. A product may require blister packaging rather than a conventional high-density polyethylene bottle.

Dispersible or sachet formulations

A dispersible tablet or powder could support patients who cannot swallow conventional tablets. This format requires control of dispersion time, sedimentation, dose recovery, and taste. It may have value in selected markets but is unlikely to justify broad commercial investment without a defined patient or channel advantage.

Fixed-dose combinations

Repaglinide and metformin combinations have been developed and marketed in some jurisdictions. The combination creates an opportunity to reduce pill burden but introduces formulation complexity because metformin is administered at a much higher dose and has different compression and dissolution characteristics.

The principal formulation issue is dose-ratio management. A bilayer tablet, multilayer tablet, or separate-pellet-in-tablet design may provide better control than a simple monolithic blend. The U.S. product PrandiMet was approved as a repaglinide/metformin hydrochloride combination product, although commercial availability and regulatory status can vary by market (FDA, 2008).

Potential combination targets include:

Combination	Commercial logic	Primary risk
Repaglinide/metformin	Reduces pill burden in patients using both agents	Large metformin dose and different release requirements
Repaglinide plus other oral antidiabetics	May address inadequate glycemic control	Clinical and regulatory justification
Repaglinide with adherence packaging	Aligns tablets with meal occasions	Packaging validation and patient-use evidence

When does repaglinide lose exclusivity and what is the Orange Book status?

Repaglinide is a mature small-molecule product. The original U.S. Prandin approval dates to the late 1990s, and generic repaglinide products have been approved for many years. The principal compound and basic immediate-release product barriers have therefore expired or ceased to provide meaningful market exclusivity.

The FDA Orange Book remains the controlling source for listed patents, exclusivity, therapeutic-equivalence codes, and approved applications. Current review should distinguish among:

1. The original Prandin drug application.
2. Generic repaglinide tablet applications.
3. Repaglinide/metformin combination applications.
4. Any later-listed formulation or method-of-use patents.
5. Patent certifications submitted by abbreviated new drug applicants.

The commercial conclusion is clear: repaglinide is not a conventional late-life-cycle product protected by an active pioneer patent. A new product would need to establish value through formulation, device, packaging, combination, or market access advantages rather than rely on the original compound estate.

Are there Paragraph IV challenges for repaglinide?

Paragraph IV risk is historically relevant to the original Prandin and combination-product approvals, but it is not the main present-day commercial issue for standard repaglinide tablets. Paragraph IV certifications allow an ANDA applicant to assert that a listed patent is invalid, unenforceable, or not infringed under the Hatch-Waxman framework.

For repaglinide, the relevant diligence questions are:

• Whether any active patent remains listed against the reference product.
• Whether the listed patent covers the active ingredient, formulation, method of use, or combination.
• Whether a generic applicant filed a Paragraph IV certification.
• Whether litigation triggered a 30-month stay.
• Whether the case ended through judgment, dismissal, or settlement.
• Whether the challenged product has already launched.

Because the product is widely genericized, a new entrant is more likely to face ordinary market competition than a meaningful patent injunction. Any proposed reformulation should receive a fresh Orange Book and FDA patent-certification review because a new NDA may generate a separate patent position even when the base drug is unprotected.

What patent litigation and settlement issues affect repaglinide?

The key patent risks are formulation and combination claims, not biosimilar issues. A company developing an improved repaglinide product should conduct a freedom-to-operate review covering:

• Particle-size and micronization claims
• Solid-state or polymorph claims
• Amorphous dispersion claims
• Cyclodextrin or co-crystal claims
• Specific excipient ratios
• Orally disintegrating and taste-masked dosage forms
• Bilayer and multilayer tablet architecture
• Repaglinide/metformin combinations
• Meal-related dosing methods
• Manufacturing processes and granulation conditions

Settlement agreements involving old generic challenges may contain launch dates, licenses, authorized-generic provisions, or restrictions that are relevant to historical entry but have limited practical effect in a mature market. The principal risk for a new developer is third-party ownership of a narrow enabling technology, particularly a solid-state or drug-delivery patent.

Is there biosimilar risk for repaglinide?

No. Repaglinide is a chemically synthesized small molecule, not a biologic. Biosimilar regulation under the Public Health Service Act does not apply. Competitive products are approved primarily through the ANDA pathway when they demonstrate pharmaceutical equivalence and bioequivalence to the reference product.

The relevant competitive risks are:

• Additional generic tablets
• Authorized generics
• Fixed-dose combinations
• Newer diabetes therapies with stronger guideline adoption
• Formulation switching among low-cost suppliers
• Regional products with different dosage forms

Repaglinide also competes indirectly with sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors, and insulin products. Its commercial position is constrained by the broader shift toward therapies with cardiovascular, renal, weight, or hypoglycemia advantages.

What are the strongest commercial opportunities for repaglinide excipients?

The most credible opportunities rank as follows:

Opportunity	Market attractiveness	Development complexity	Patent potential
Low-cost immediate-release tablet	High volume, low margin	Low	Low
Improved 0.5 mg content uniformity	Moderate	Moderate	Moderate if process-linked
Fast-dissolving tablet	Moderate	Moderate	Moderate
Orally disintegrating tablet	Niche to moderate	Moderate	Moderate
Repaglinide/metformin combination	Market-dependent	High	Moderate
Amorphous solid dispersion	Premium niche	High	High
Pediatric or geriatric dispersible product	Niche	Moderate to high	Moderate
Meal-linked adherence packaging	Niche	Low to moderate	Low to moderate

Excipient suppliers

Excipient suppliers can create value through a platform rather than a single ingredient. Attractive offerings include:

• Co-processed direct-compression excipients for low-dose APIs
• High-functionality superdisintegrants
• Low-peroxide and low-moisture grades
• Spray-dried mannitol or lactose systems
• Taste-masking polymer platforms
• Ready-to-use premixes for content uniformity
• Surfactant-polymer systems for dissolution enhancement

The best commercial claim is usually process performance: faster development, improved blend uniformity, lower tablet weight, or more robust dissolution. A supplier that can demonstrate these benefits in repaglinide development batches may use the molecule as a model low-dose, poorly soluble API.

How does repaglinide compare with competing diabetes drugs?

Repaglinide has a low-cost and flexible meal-time dosing profile, but its competitive position is weaker on outcomes-based differentiation.

Product class	Main advantage over repaglinide	Repaglinide counterposition
Metformin	First-line status and low cost	Repaglinide can address meal-related insulin secretion
Sulfonylureas	Broad availability and low price	Repaglinide has shorter action and meal-linked dosing
DPP-4 inhibitors	Low hypoglycemia risk and convenient dosing	Repaglinide has lower acquisition cost in generic markets
GLP-1 receptor agonists	Weight loss and stronger metabolic differentiation	Repaglinide is oral and inexpensive
SGLT2 inhibitors	Cardiovascular and renal benefits	Repaglinide is useful where cost dominates
Insulin	Potent glucose lowering	Repaglinide avoids injections in selected patients

The product is most commercially defensible in price-sensitive markets, patients with irregular meal schedules, and settings where newer agents are unavailable or unaffordable. Its main clinical weakness is hypoglycemia risk, particularly when meals, dose timing, and renal or hepatic function are not well managed.

What generic launch scenarios exist for repaglinide?

A new entrant has three practical launch models.

Commodity generic launch

This model uses a conventional tablet and competes on cost, supply reliability, and regulatory execution. It requires minimal formulation innovation but faces severe price pressure.

Differentiated oral product

An ODT, dispersible tablet, or smaller tablet can target adherence and swallowing barriers. The commercial case improves if the product qualifies for a distinct product code, secures channel differentiation, or obtains market-specific reimbursement support.

Combination or platform product

A repaglinide/metformin product can reduce pill burden. The opportunity is stronger in markets where both components remain widely prescribed and combination products have reimbursement support. Manufacturing complexity and clinical positioning are the principal barriers.

What is the revenue exposure and market outlook for repaglinide?

Revenue exposure is generally low for originator companies and concentrated among generic manufacturers, contract manufacturers, and regional distributors. The product has limited premium pricing power because the active ingredient and standard tablet format are mature.

Commercial value depends on:

• Number of approved generic suppliers
• Procurement contracts
• Local reimbursement
• Availability of all strengths
• Manufacturing cost per tablet
• Stability and packaging requirements
• Market demand for metformin combinations
• Competition from newer diabetes therapies

A conventional repaglinide product is unlikely to support a large standalone innovation program. An excipient-led reformulation can be commercially viable when it uses an existing manufacturing platform, addresses a defined adherence problem, or creates a combination product with clear reimbursement value.

Key Takeaways

• Repaglinide is a mature generic small molecule with limited residual compound-level exclusivity.
• The central formulation problem is low solubility combined with a very low dose.
• Immediate-release tablets should prioritize wetting, rapid disintegration, dissolution, and content uniformity.
• The 0.5 mg strength creates the greatest blend-uniformity and segregation risk.
• ODT, dispersible, taste-masked, and smaller-tablet products offer the clearest formulation differentiation.
• Repaglinide/metformin combinations provide a commercially relevant but technically more complex opportunity.
• Biosimilar risk does not apply; competition comes from generics, combinations, and newer diabetes therapies.
• Patent value is more likely in solid-state, drug-delivery, formulation, or manufacturing claims than in the original molecule.
• Excipient suppliers have an opportunity to sell co-processed low-dose platforms, superdisintegrants, taste-masking systems, and dissolution-enhancement technologies.
• Commodity generic launches face low margins unless supported by manufacturing scale, supply reliability, or geographic access.

FAQs

Can repaglinide be formulated as an orally disintegrating tablet?

Yes. Its low dose is compatible with an ODT format. The formulation must control taste, friability, moisture sensitivity, disintegration time, and dissolution. Mannitol, crospovidone, polymeric taste barriers, and moisture-protective packaging are plausible development tools.

Which excipient is most important for repaglinide dissolution?

No single excipient is universally controlling. A superdisintegrant improves tablet breakup, but a surfactant, particle-size strategy, or amorphous dispersion may be required when dissolution remains limited after disintegration.

Is a sustained-release repaglinide product commercially attractive?

Usually not for the existing meal-linked use pattern. Repaglinide is designed for administration before meals, so an extended-release product would require a distinct clinical rationale, exposure profile, and regulatory strategy.

Can repaglinide and metformin be placed in one tablet?

Yes. The combination has been developed as a fixed-dose product. A bilayer or multilayer design may be preferable where the two drugs require different compression, dissolution, or excipient environments.

Does repaglinide have an opportunity in pediatric diabetes?

The opportunity is limited and would require a specific clinical development rationale. A dispersible or liquid-compatible dosage form could address administration needs, but pediatric labeling, palatability, dosing flexibility, and safety data would create substantial regulatory requirements.

References

1. U.S. Food and Drug Administration. (2008). PrandiMet (repaglinide and metformin hydrochloride) tablets: Prescribing information. FDA.

2. U.S. Food and Drug Administration. (2023a). Repaglinide tablets: Prescribing information. FDA.

3. U.S. Food and Drug Administration. (2023b). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. DailyMed. (2023). Repaglinide tablet prescribing information. U.S. National Library of Medicine.

5. National Center for Biotechnology Information. (2024). PubChem compound summary for repaglinide. PubChem.