List of Excipients in Branded Drug DILTIAZEM HYDROCHLORIDE

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
PuraCap Laboratories LLC	DILTIAZEM HYDROCHLORIDE	diltiazem hydrochloride	24658-174	CELLULOSE, MICROCRYSTALLINE
PuraCap Laboratories LLC	DILTIAZEM HYDROCHLORIDE	diltiazem hydrochloride	24658-174	D&C RED NO. 28
PuraCap Laboratories LLC	DILTIAZEM HYDROCHLORIDE	diltiazem hydrochloride	24658-174	ETHYL ACRYLATE AND METHYL METHACRYLATE COPOLYMER
PuraCap Laboratories LLC	DILTIAZEM HYDROCHLORIDE	diltiazem hydrochloride	24658-174	FD&C BLUE NO. 1

Generic Drugs Containing DILTIAZEM HYDROCHLORIDE

Company	Ingredient	NDC	Excipient
Teva Pharmaceuticals USA Inc	diltiazem hydrochloride	0093-0318	FD&C YELLOW NO. 6
Teva Pharmaceuticals USA Inc	diltiazem hydrochloride	0093-0318	HYPROMELLOSE
Teva Pharmaceuticals USA Inc	diltiazem hydrochloride	0093-0318	LACTOSE MONOHYDRATE
Teva Pharmaceuticals USA Inc	diltiazem hydrochloride	0093-0318	MAGNESIUM STEARATE

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

# Of NDCs	Excipient
1	1-PROPOXY-2-PROPANOL
15	ACETYLTRIBUTYL CITRATE
1	ALLYL SUCROSE
4	ALUMINUM OXIDE

Diltiazem Hydrochloride Excipient Strategy and Commercial Opportunities

Last updated: August 10, 2026

Diltiazem hydrochloride is a mature, off-patent calcium-channel blocker with established immediate-release and extended-release products. The main commercial opportunity is not new-molecule exclusivity. It is differentiated delivery: once-daily release, sprinkle-compatible capsules, lower pill burden, pediatric or dysphagia-friendly presentations, and robust control of food and alcohol effects. Excipient selection is central because release performance, dose dumping, bioequivalence, and manufacturing cost determine the value of a diltiazem product.

What is the commercial status of diltiazem hydrochloride?

Diltiazem hydrochloride is approved for hypertension, chronic stable angina, and selected supraventricular tachyarrhythmias. U.S. products include immediate-release tablets and several extended-release dosage forms, including capsules and tablets marketed by multiple generic manufacturers.[1][2]

Attribute	Diltiazem hydrochloride
Drug class	Benzothiazepine calcium-channel blocker
Primary U.S. indications	Hypertension, angina, rate control in selected arrhythmias
Dosage forms	Immediate-release tablets, extended-release capsules, extended-release tablets
Regulatory pathway for generics	Abbreviated New Drug Application, or ANDA
Biosimilar exposure	None; diltiazem is a small molecule
Composition-of-matter position	Long expired
Main remaining IP opportunity	Formulation, release-control, manufacturing, device, and method-of-use claims
Commercial market structure	Mature generic market with differentiated extended-release products
Key technical challenge	Matching reference-product release and pharmacokinetics while controlling alcohol and food effects

The molecule’s age limits the value of conventional patent strategies. Product value depends on manufacturing scale, formulary access, dosage-form differentiation, and regulatory execution.

What excipients are used in diltiazem hydrochloride products?

Diltiazem products generally use excipients in four categories: fillers and binders, coating materials, release-control polymers, and capsule or tablet finishing agents.

Immediate-release tablets

Immediate-release tablets commonly use:

• Microcrystalline cellulose as a diluent and compression aid
• Lactose, starch, or dibasic calcium phosphate as fillers
• Povidone or pregelatinized starch as a binder
• Croscarmellose sodium or sodium starch glycolate as a disintegrant
• Magnesium stearate or stearic acid as a lubricant
• Colloidal silicon dioxide as a glidant
• Film-coating systems based on hypromellose, polyethylene glycol, titanium dioxide, talc, and colorants

For an immediate-release generic, excipient novelty has limited commercial value. The development priority is a stable, low-cost tablet with rapid dissolution, acceptable content uniformity, and low sensitivity to compression force.

Extended-release capsules

Extended-release diltiazem capsules commonly contain coated pellets or beads rather than a single monolithic tablet. Typical excipient functions include:

Functional role	Common excipient classes
Pellet core	Sugar spheres, microcrystalline cellulose, starch
Drug-layer binder	Povidone, hydroxypropyl cellulose, hypromellose
Diffusion-control coating	Ethylcellulose, ammonio methacrylate copolymers
Pore former	Hypromellose, polyethylene glycol, water-soluble polymers
Anti-tacking agent	Talc, colloidal silicon dioxide
Capsule shell	Gelatin, titanium dioxide, colorants
Optional fill matrix	Microcrystalline cellulose, starch, lactose

Multiparticulate systems allow manufacturers to tune release through pellet size, polymer thickness, coating composition, and the proportion of immediate-release versus controlled-release units. They also create opportunities for sprinkle administration if the pellets remain intact when removed from the capsule.

Extended-release tablets

Extended-release tablets may use hydrophilic matrix systems or coated drug-containing units compressed into a tablet. Relevant polymers include:

• Hypromellose
• Hydroxypropyl cellulose
• Polyethylene oxide
• Carbomers
• Ethylcellulose
• Methacrylate copolymers

Hydrophilic matrices are generally less expensive than multiparticulate capsules but may be more sensitive to tablet geometry, compression force, hydration, gastrointestinal transit, and food effects. Coated-unit tablets can combine multiparticulate release control with tablet manufacturing, but they require protection against pellet rupture during compression.

Which excipient strategies provide the strongest commercial differentiation?

The strongest strategies target a defined clinical or manufacturing problem rather than simply replacing one filler with another.

1. Multiparticulate release control

Multiparticulate capsules can provide:

• More reproducible gastrointestinal distribution
• Lower risk of complete dose release from a single damaged unit
• Potential sprinkle administration
• Independent control of release fractions
• Better opportunities for layered intellectual property

A commercial product could combine immediate-release pellets with several populations of extended-release pellets. That approach can create a controlled onset followed by sustained plasma exposure. The tradeoff is higher coating and analytical cost.

2. Alcohol-resistant release

Alcohol-induced dose dumping is a major risk for modified-release products. Ethanol can plasticize or disrupt polymer coatings, alter pore formation, or accelerate drug diffusion. A robust formulation should be evaluated in hydroalcoholic dissolution media at clinically relevant concentrations and under stressed manufacturing conditions.

Potential strategies include:

• Combining hydrophilic and hydrophobic polymers
• Increasing coating-film integrity
• Using polymer blends with controlled permeability
• Applying a protective outer layer
• Reducing residual solvent and coating variability
• Designing pellets with redundant release-control layers

A formulation that maintains release in the presence of alcohol can support a stronger regulatory and commercial position than a lower-cost formulation with a narrow release margin.

3. Sprinkle-compatible capsules

Dysphagia and adherence are practical issues in cardiovascular therapy. A capsule containing stable coated pellets may be opened and sprinkled over soft food, provided the product labeling and supporting data permit that use.

The formulation must preserve:

• Pellet integrity during capsule opening
• Dose uniformity after transfer
• Release performance after contact with food
• Stability under short-term exposure to moisture
• Absence of crushing or chewing requirements

Sprinkle products can target older adults, patients with swallowing limitations, and institutional care settings. The commercial advantage is stronger when the product has a clearly supported administration method rather than an informal off-label use.

4. Low-cost direct-compression tablets

For immediate-release or selected extended-release products, a direct-compression platform can reduce granulation, drying, and processing costs. Excipient selection should focus on:

• Consistent powder flow
• Low lubricant sensitivity
• Robust tablet hardness
• Rapid scale-up
• Low hygroscopicity
• Compatibility with high-speed presses

A co-processed excipient system may improve manufacturability, but it does not by itself create meaningful patent protection. The value comes from lower cost, fewer process steps, and consistent dissolution.

5. Liquid and dysphagia-friendly presentations

Diltiazem hydrochloride’s aqueous solubility can support liquid development, but chemical and microbiological stability become central issues. A commercial liquid would require control of:

• pH-dependent stability
• Preservative effectiveness
• Container adsorption
• Taste and mouthfeel
• Dose measurement
• Compatibility with enteral feeding systems

A liquid or dispersible product may support a 505(b)(2) strategy if it introduces a clinically meaningful dosage form or administration method. The commercial opportunity is narrower than for generic tablets because development, labeling, and distribution costs are higher.

What formulation patents could protect diltiazem hydrochloride products?

The molecule itself does not provide a meaningful new chemical entity or composition-of-matter opportunity. The relevant patent categories are:

Patent category	Potential claim subject
Release-control formulation	Polymer composition, coating thickness, pellet architecture, release profile
Multiparticulate product	Immediate-release and delayed-release pellet populations
Alcohol-resistant product	Release profile in hydroalcoholic media
Sprinkle dosage form	Pellets that maintain performance after capsule opening
Tablet matrix	Polymer concentration, tablet geometry, compression conditions
Manufacturing process	Drug layering, coating sequence, curing, drying, pellet-size control
Stability	Moisture-control system, packaging, excipient combination
Method of use	Once-daily administration, reduced adverse effects, selected patient populations
Device or package	Unit-dose system, administration aid, moisture-barrier package

Patent strength depends on claim breadth and reproducibility. A patent claiming only a specific polymer grade or a narrow dissolution result is usually easier to design around than a patent covering a defined multiparticulate architecture with clinically relevant pharmacokinetic properties.

How strong is the diltiazem hydrochloride patent estate?

The core estate is weak because diltiazem has been marketed for decades and generic competition is established. The residual estate is fragmented and product-specific.

A formulation patent is commercially stronger when it has:

1. A technically necessary feature, such as a defined release profile or alcohol-resistant coating.
2. Claims that cover multiple polymer grades and manufacturing routes.
3. Supporting stability and pharmacokinetic data.
4. A clear distinction from reference products.
5. Claims that are difficult to avoid without sacrificing product performance.

Method-of-use patents have limited value in a mature hypertension and angina market unless they address a narrow, enforceable patient population or a differentiated dosing schedule. Manufacturing patents can be valuable when the process materially improves yield, coating uniformity, or cost, but enforcement may be difficult if production occurs outside the jurisdiction.

What is the Orange Book status of diltiazem hydrochloride?

Diltiazem hydrochloride products approved as new drugs or listed reference products may appear in the FDA Orange Book, while many generic products are listed through their associated ANDAs.[3] Orange Book relevance is product-specific. A listed patent must be connected to the approved drug product and may cover formulation, method of use, or other approved characteristics.

For diltiazem:

• No current composition-of-matter exclusivity is expected.
• Generic entry is already established.
• Remaining listed patents, if any, are likely to relate to specific extended-release products or approved uses.
• The practical risk is product-by-product, not molecule-wide.
• A proposed generic must assess listed patents and certifications under the ANDA pathway.

The commercial value of an Orange Book-listed formulation patent is highest when the corresponding reference product retains meaningful prescription volume. A patent covering a declining product with many therapeutic substitutes has limited negotiating leverage.

When does diltiazem hydrochloride lose exclusivity?

Diltiazem’s original exclusivity expired decades ago. The molecule is available through generic products, and the market does not present a biosimilar-style exclusivity barrier.

The relevant timing questions now concern:

• Expiration of any surviving formulation patents
• Pediatric exclusivity, if granted for a specific product
• Regulatory exclusivity attached to a later-approved dosage form
• ANDA approval timing
• Paragraph IV litigation and settlement restrictions
• Manufacturing readiness and commercial launch

Unlike a recently approved product, diltiazem does not have a single molecule-level loss-of-exclusivity event. Generic competition has already occurred. A new entrant must therefore win through price, supply reliability, dosage-form differentiation, or channel strategy.

Which companies are challenging diltiazem hydrochloride products?

The market includes numerous generic manufacturers and suppliers. Competition has historically involved manufacturers such as Actavis, Mylan, Sandoz, Teva, Zydus, Lupin, Sun Pharmaceutical Industries, and other ANDA sponsors, depending on product, strength, and market period.

A current competitive review should distinguish:

• Immediate-release tablets
• Extended-release capsules
• Extended-release tablets
• Brand or authorized-generic supply
• Manufacturer-specific strengths
• National versus limited distribution
• Products with current commercial availability

Paragraph IV challenges are most commercially relevant when a branded extended-release product has remaining formulation patents and substantial sales. For mature diltiazem products, the value of a challenge depends more on the number of approved suppliers and the reference product’s remaining market share than on the molecule itself.

What generic entry risks exist for diltiazem hydrochloride?

Generic entry risk is high for conventional immediate-release tablets and established extended-release products. The main barriers are regulatory and operational rather than chemical.

Regulatory risks

FDA review can focus on:

• Comparative dissolution across multiple media
• Fed and fasted pharmacokinetics
• Dose proportionality across strengths
• Alcohol-induced dose dumping
• Stability and moisture sensitivity
• Capsule-opening or sprinkle performance
• In vitro-in vivo correlation
• Batch-to-batch release variability

Extended-release products may require more complex bioequivalence evidence than immediate-release tablets. Differences in excipient composition are permissible, but they cannot produce clinically meaningful differences in exposure or release.

Manufacturing risks

The principal manufacturing barriers include:

• Drug-layering uniformity
• Pellet-size distribution
• Coating thickness control
• Polymer curing
• Residual solvent control
• Capsule fill-weight accuracy
• Segregation during blending
• Compression damage to coated units
• Packaging protection against moisture

These factors can make a technically simple formulation difficult to commercialize at scale.

How does diltiazem compare with competing cardiovascular drugs?

Diltiazem competes with amlodipine, verapamil, beta blockers, and other antihypertensive or rate-control products. Amlodipine has a simpler once-daily tablet profile and generally lower formulation complexity. Verapamil competes more directly in certain rate-control and extended-release segments but also requires release-control technologies.

Product characteristic	Diltiazem	Amlodipine	Verapamil
Core market maturity	High	High	High
Extended-release complexity	Moderate to high	Low for standard tablets	Moderate to high
Formulation opportunity	Pellets, matrices, sprinkle, alcohol resistance	Taste, low-dose uniformity, combination products	Release control and dose flexibility
Biosimilar risk	None	None	None
Generic price pressure	High	Very high	High
Differentiation potential	Moderate	Low to moderate	Moderate
Main commercial lever	Dosing convenience and reliable release	Cost and combination therapy	Controlled exposure and tolerability

Diltiazem has greater excipient-driven differentiation potential than a conventional amlodipine tablet because its extended-release products depend more heavily on release architecture.

What licensing opportunities exist for diltiazem excipient technology?

Licensing opportunities are most credible in platform technologies that apply beyond diltiazem. Relevant assets include:

• Multiparticulate coating systems
• Alcohol-resistant modified-release polymers
• Low-cost aqueous coating processes
• Sprinkle-compatible pellet platforms
• Taste-masking and oral-liquid systems
• Co-processed excipients for direct compression
• Moisture-barrier packaging
• Continuous manufacturing for coated pellets

A diltiazem-only license is unlikely to command a high value unless it includes a differentiated product with regulatory approval, clinical data, or strong market access. The stronger transaction structure is a platform license with diltiazem as the first or representative product.

What is the revenue exposure and market opportunity?

Diltiazem is a mature, price-sensitive generic market. Revenue exposure is concentrated in:

• High-volume immediate-release tablets
• Once-daily extended-release products
• Hospital and institutional supply
• Mail-order and retail pharmacy channels
• Products with reliable availability during generic shortages

Commercial upside from a standard generic is limited. A differentiated extended-release product can support better pricing if it offers:

• Once-daily dosing
• Lower variability
• Sprinkle administration
• Lower food or alcohol sensitivity
• A supply advantage
• A clinically useful strength or dosage form not consistently available

The most defensible opportunity is a technically differentiated product with a defined target population and a manufacturing process that maintains margin after generic price erosion.

What is the recommended excipient development strategy?

A practical development sequence is:

1. Select a multiparticulate or matrix platform based on the target dosing interval.
2. Screen hydrophilic and hydrophobic polymers for release robustness.
3. Test dissolution across pH conditions and hydroalcoholic media.
4. Evaluate food effects and fed-fast variability.
5. Assess capsule-opening and sprinkle performance if relevant.
6. Confirm compatibility using stress stability, moisture, and thermal studies.
7. Optimize coating and curing for scale-up.
8. Compare the target profile with the relevant reference product.
9. Map formulation features to potential patent claims.
10. Select the ANDA or 505(b)(2) pathway based on the proposed dosage form and labeling.

The preferred commercial design is usually a controlled-release multiparticulate capsule with a robust polymer coating, low manufacturing complexity, and a permitted sprinkle option. Immediate-release products remain attractive for cost-focused supply, but they offer limited defensibility.

Key Takeaways

• Diltiazem hydrochloride is a long-established generic molecule with no meaningful composition-of-matter exclusivity.
• The strongest opportunities are extended-release formulation, sprinkle delivery, alcohol-resistant release, and manufacturing-cost reduction.
• Multiparticulate capsules provide the broadest excipient-driven differentiation.
• Ethylcellulose, methacrylate copolymers, hypromellose, povidone, microcrystalline cellulose, sugar spheres, and related coating excipients are central to product design.
• Orange Book and Paragraph IV risk is product-specific and concentrated in surviving formulation or method patents.
• Biosimilar risk does not apply because diltiazem is a small molecule.
• A standard immediate-release generic faces high price competition and limited patent value.
• A differentiated extended-release product can command greater commercial value if it demonstrates robust dissolution, low food and alcohol sensitivity, and a clear administration advantage.
• Licensing value is strongest for platform excipient and coating technologies with applications across multiple modified-release drugs.

FAQs

Can diltiazem hydrochloride be formulated as a once-daily product?

Yes. Once-daily diltiazem products use extended-release matrices, coated pellets, or other controlled-release architectures. The product must demonstrate appropriate pharmacokinetics and release control.

Which excipient is best for diltiazem extended release?

There is no universal best excipient. Ethylcellulose and methacrylate copolymers are useful for diffusion-controlled coatings, while hypromellose and polyethylene oxide are common hydrophilic matrix polymers. The optimal system depends on target release, dosage form, processing method, and alcohol resistance.

Is diltiazem hydrochloride suitable for a 505(b)(2) product?

Potentially. A 505(b)(2) strategy may be relevant for a novel liquid, sprinkle product, alternative release profile, or other dosage form that relies partly on an approved product while requiring new clinical or bridging evidence.

Does diltiazem hydrochloride have biosimilar competition?

No. Biosimilar provisions apply to biological products. Diltiazem hydrochloride is a chemically synthesized small molecule and competes through generic drug pathways.

What is the biggest technical risk in developing diltiazem extended release?

The largest risk is failure to maintain the intended release profile across manufacturing scale, food conditions, and hydroalcoholic exposure. Coating uniformity, pellet damage, polymer variability, and dissolution drift can affect bioequivalence and regulatory approval.

References

1. U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/

2. National Library of Medicine. (2024). DailyMed: Diltiazem hydrochloride drug labels. https://dailymed.nlm.nih.gov/dailymed/

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/

4. U.S. Food and Drug Administration. (2015). Guidance for industry: ANDAs for certain highly soluble, highly permeable drugs. https://www.fda.gov/regulatory-information

5. U.S. Food and Drug Administration. (2020). Guidance for industry: Extended release oral dosage forms: Development, evaluation, and application of in vitro/in vivo correlations. https://www.fda.gov/regulatory-information

6. U.S. Food and Drug Administration. (2024). Inactive ingredient database. https://www.accessdata.fda.gov/scripts/cder/iig/