List of Excipients in Branded Drug ALOGLIPTIN AND METFORMIN HYDROCHLORIDE

« Back to Dashboard

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Padagis Israel Pharmaceuticals Ltd	ALOGLIPTIN AND METFORMIN HYDROCHLORIDE	alogliptin and metformin hydrochloride	45802-169	CELLULOSE, MICROCRYSTALLINE	2026-07-27
Padagis Israel Pharmaceuticals Ltd	ALOGLIPTIN AND METFORMIN HYDROCHLORIDE	alogliptin and metformin hydrochloride	45802-169	CROSPOVIDONE	2026-07-27
Padagis Israel Pharmaceuticals Ltd	ALOGLIPTIN AND METFORMIN HYDROCHLORIDE	alogliptin and metformin hydrochloride	45802-169	FERRIC OXIDE YELLOW	2026-07-27

Alogliptin and Metformin Hydrochloride Excipient Strategy, Formulation Opportunities, and Commercial Outlook

Last updated: October 18, 2026

Alogliptin/metformin hydrochloride is an immediate-release fixed-dose combination for adults with type 2 diabetes. The product pairs a low-dose DPP-4 inhibitor, alogliptin benzoate equivalent to 12.5 mg alogliptin, with high-dose metformin hydrochloride at 500 mg or 1,000 mg per tablet. The main formulation challenge is metformin’s large dose, hygroscopicity, gastrointestinal tolerability, and dissolution performance. The strongest commercial opportunities are generic or regional fixed-dose combinations, lower-cost manufacturing, improved tablet swallowability, and differentiated presentations that preserve immediate-release exposure.

The U.S. reference product is Kazano. The European product is Vipdomet. Both products use conventional immediate-release tablet technology rather than an advanced delivery system. The core excipient platform is therefore accessible to generic manufacturers, but bioequivalence, stability, dissolution, process control, and regulatory requirements remain material barriers.

What is alogliptin and metformin hydrochloride used for?

Alogliptin/metformin hydrochloride is used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is not indicated for type 1 diabetes or diabetic ketoacidosis.

Alogliptin inhibits dipeptidyl peptidase-4, increasing endogenous incretin activity. Metformin reduces hepatic glucose production and improves insulin sensitivity. The combination targets complementary mechanisms without adding insulin or a sulfonylurea.

The marketed U.S. strengths are:

Product strength	Alogliptin component	Metformin hydrochloride component	Dosage form
Kazano 12.5/500	12.5 mg alogliptin	500 mg	Immediate-release film-coated tablet
Kazano 12.5/1,000	12.5 mg alogliptin	1,000 mg	Immediate-release film-coated tablet

The alogliptin component is supplied as alogliptin benzoate, calculated as the alogliptin equivalent. Patients with renal impairment require dose adjustment, and the fixed-dose combination is unsuitable where the required alogliptin or metformin dose does not match an available strength. The product is contraindicated in severe renal impairment and in acute or chronic metabolic acidosis under the U.S. labeling framework.[1]

What excipients are used in alogliptin/metformin tablets?

The reference formulation uses a conventional directly compressible or granulated tablet platform built around a diluent, binder, disintegrant, lubricant, and film coat.

The U.S. Kazano label identifies the following inactive ingredients:

Formulation function	Representative excipient
Diluent and compression aid	Mannitol
Binder	Povidone
Disintegrant	Crospovidone
Lubricant	Magnesium stearate
Film former	Hypromellose
Coating opacifier	Titanium dioxide
Colorants	Iron oxides
Coating aid or anti-tacking agent	Talc

The precise colorant system can vary by strength and jurisdiction. Generic developers must rely on the current reference-product labeling and their own approved formulation rather than assume that all strengths or markets use an identical coating composition.[1]

Why does mannitol have commercial value in this formulation?

Mannitol is useful because it provides acceptable tablet compactability, a relatively clean sensory profile, and lower hygroscopicity than some alternative polyols. Those properties matter in a formulation containing metformin hydrochloride, which is highly water soluble and can complicate granulation, drying, sticking, and tablet robustness.

Mannitol also supports a differentiated excipient strategy:

• spray-dried or granulated mannitol can improve flow and compression;
• co-processed mannitol systems can reduce segregation risk;
• low-moisture grades can support stability;
• particle-size selection can improve blend uniformity and tablet weight control.

The commercial benefit is greatest for the 1,000 mg strength, where the metformin load magnifies tablet-size and manufacturing problems.

What is the role of crospovidone?

Crospovidone provides rapid wicking and tablet breakup. The product must release both alogliptin and metformin within an immediate-release dissolution profile. Excessive disintegrant can reduce tablet hardness or increase friability, while insufficient disintegrant can delay release after compression at high tablet forces.

Generic manufacturers can evaluate crospovidone grade, particle size, intra- versus extra-granular addition, and total concentration. Those changes can create a meaningful process-development program without altering the active ingredients.

What excipient strategy is best for alogliptin/metformin?

The most defensible strategy is a low-moisture, immediate-release formulation with controlled particle-size distribution and a robust film coat.

Recommended formulation priorities

Development issue	Preferred strategy	Commercial rationale
High metformin dose	High-load diluent system with efficient compression	Controls tablet size and production cost
Blend uniformity	Narrow particle-size distribution and validated mixing order	Protects low-dose alogliptin content uniformity
Moisture sensitivity	Low-water processing or tightly controlled aqueous granulation	Reduces stability and sticking risks
Tablet disintegration	Crospovidone optimization	Supports rapid release without excessive friability
Lubrication	Controlled magnesium stearate mixing time	Limits dissolution slowdown and ejection problems
Patient acceptability	Thin, low-friction film coat and tablet-shape optimization	Addresses the large metformin tablet burden
Stability	Moisture-barrier blister or high-performance bottle closure	Protects product through distribution
Manufacturing scale-up	Robust design space for compression force and dwell time	Reduces batch failure risk

The primary technical risk is not alogliptin loading. Alogliptin is present at a much lower mass than metformin, so the critical quality attributes are content uniformity, segregation control, and API-excipient distribution. Metformin controls tablet mass, dissolution behavior, and patient-perceived size.

What formulations are protected by alogliptin/metformin patents?

The original commercial product is an immediate-release fixed-dose tablet containing alogliptin and metformin. Patent protection may cover the active combination, pharmaceutical compositions, dosing methods, and manufacturing processes. The relevant claims must be assessed by jurisdiction and by the specific product strength.

The United States Orange Book should be used to confirm current listed patents and regulatory exclusivity for Kazano. Orange Book status is product-specific and can change when patents expire, delistings occur, or the application is discontinued.[2]

The commercially important claim categories are:

1. The combination of alogliptin or an alogliptin salt with metformin.
2. Specific dose ratios or dosage strengths.
3. Pharmaceutical compositions containing the two active ingredients.
4. Treatment of type 2 diabetes using the combination.
5. Salt forms, crystalline forms, or impurity-controlled materials.
6. Manufacturing or blending processes, where separately patented.

Excipient claims are less likely to create a broad barrier for a conventional generic because many inactive ingredients can be substituted if the resulting product meets quality and bioequivalence requirements. A patent directed to a specific excipient ratio, granulation process, coating composition, or dissolution profile could still affect design freedom.

When does alogliptin/metformin lose exclusivity?

The relevant exclusivity timeline has several components:

Exclusivity category	Relevance
New chemical entity exclusivity	Applies to the original active ingredient, not necessarily the later fixed-dose combination
Fixed-combination approval	The combination may receive separate regulatory protection from the underlying single agents
Listed patents	May protect the combination, composition, method of use, or manufacturing process
Pediatric exclusivity	Can add six months if granted
Regulatory data protection outside the U.S.	Depends on regional rules and product authorization history
Patent-term adjustment or extension	Can change the effective U.S. expiry date

A precise generic-entry date cannot be inferred from the approval date alone. It requires a current Orange Book patent record, any Paragraph IV litigation, settlement terms, pediatric extensions, and the status of the reference application.

What is the FDA regulatory status of Kazano?

Kazano was approved by the FDA as an oral fixed-dose combination of alogliptin benzoate and metformin hydrochloride. The product was reviewed under NDA 022426.[1]

The U.S. label identifies the product as an immediate-release tablet in 12.5/500 mg and 12.5/1,000 mg strengths. The product requires renal-function assessment because both dose selection and metformin safety depend on kidney function.

Regulatory considerations for a generic include:

• immediate-release dosage-form requirements;
• strength-specific formulation performance;
• alogliptin content uniformity;
• metformin dissolution;
• fed and fasting bioequivalence, where required;
• renal dosing information;
• lactic acidosis warnings associated with metformin;
• heart-failure and pancreatitis warnings associated with the alogliptin class labeling;
• adequate labeling for concomitant insulin or sulfonylurea use.

Kazano’s commercial status should be distinguished from FDA approval status. A product can remain approved while marketing is discontinued or limited. The FDA’s product databases and current labeling provide the controlling regulatory record.[1,2]

What is the European regulatory status of Vipdomet?

Vipdomet contains alogliptin benzoate and metformin hydrochloride in fixed-dose film-coated tablets. The European Medicines Agency describes the product as an add-on treatment for adults with type 2 diabetes when metformin alone does not provide adequate control or when patients are already receiving the two components separately.[3]

European development and commercialization depend on the centralized marketing authorization record, national reimbursement decisions, and the marketing authorization holder’s supply strategy. European markets may offer opportunities for regional generic or hybrid products, but substitution rules, reference pricing, and country-specific reimbursement can limit the value of a simple formulation copy.

How strong is the patent estate for alogliptin/metformin?

The patent estate is likely more vulnerable at the formulation level than at the active-combination level. A conventional immediate-release tablet has multiple design-around options for diluents, binders, disintegrants, coatings, and packaging.

Patent strength should be assessed across five dimensions:

Dimension	Risk assessment
Active combination	Potentially material if claims cover the specific alogliptin-metformin combination
Dose strengths	Moderate; strength-specific claims can narrow design options
Formulation	Usually designable if claims do not require a narrow excipient composition
Method of use	Relevant to ANDA certification and labeling strategy
Manufacturing process	Relevant if the process is necessary for acceptable content uniformity or dissolution

A generic company can reduce formulation risk by using a non-infringing excipient matrix, avoiding claimed ratios, and validating an independent manufacturing process. A freedom-to-operate review must include granted patents, pending applications, continuations, terminal disclaimers, and jurisdiction-specific claim scope.

Which companies are challenging alogliptin/metformin exclusivity?

Publicly confirmed challenger activity should be verified through FDA ANDA records, Paragraph IV litigation dockets, and Orange Book certifications. A reliable market assessment should not treat an ANDA filing, a patent challenge, or a tentative approval as equivalent to commercial launch.

The practical challenger groups are:

• large generic manufacturers with established diabetes portfolios;
• regional manufacturers in markets where Vipdomet or equivalent products remain commercially relevant;
• contract development and manufacturing organizations offering high-dose metformin tablet platforms;
• specialty pharmaceutical companies pursuing authorized-generic or licensing arrangements.

Where no active public litigation or launch notice is identified, the commercial conclusion should be stated as limited visible challenger activity rather than assumed absence of competition.

What generic entry risks exist?

Generic entry risk is substantial once applicable combination patents and regulatory protections no longer block approval. The active ingredients are small molecules, the dosage form is an immediate-release tablet, and the excipient platform is conventional.

The principal risks for a generic applicant are operational rather than scientific:

1. Large tablet size, particularly for the 1,000 mg metformin strength.
2. Blend segregation caused by the low alogliptin loading.
3. Compression defects, sticking, and capping.
4. Dissolution changes caused by over-lubrication.
5. Stability loss under high humidity.
6. Bioequivalence failure from an altered release profile.
7. Labeling constraints caused by renal dosing and combination-use limitations.
8. Limited commercial pricing power after multiple launches.

The highest-risk launch scenario is a rapid, multi-supplier generic entry that drives the product toward commodity pricing. A more favorable scenario involves a small number of approved suppliers, differentiated packaging, strong regional distribution, or an authorized-generic agreement.

What commercial opportunities exist for excipient suppliers?

Excipient suppliers have several practical entry points.

High-functionality mannitol

A directly compressible or co-processed mannitol grade can reduce granulation steps, improve tablet strength, and support high drug loading. The most attractive value proposition is lower total manufacturing cost rather than a novel therapeutic claim.

Low-moisture processing systems

A low-water formulation can reduce drying requirements and mitigate metformin-related process variability. This is relevant to manufacturers operating in humid climates or using high-throughput compression lines.

Improved film-coating systems

A thinner, faster-drying, lower-tack coating can reduce cycle time and improve appearance. The coating must preserve immediate release and avoid increasing tablet size.

Packaging and moisture control

High-barrier blister films, desiccant-integrated bottles, and improved closure systems can support shelf life. Packaging is often more defensible commercially than a routine excipient substitution because it can address distribution conditions directly.

Pediatric and geriatric usability

The fixed-dose combination is not naturally suited to flexible dosing because alogliptin and metformin requirements vary by renal function and tolerability. Commercial opportunities are therefore stronger in swallowability, tablet geometry, and packaging than in pediatric innovation.

How does alogliptin/metformin compare with competing diabetes combinations?

Alogliptin/metformin competes with other DPP-4 inhibitor/metformin combinations, including sitagliptin/metformin and linagliptin/metformin, as well as newer metformin combinations with SGLT2 inhibitors or GLP-1 receptor agonists.

Attribute	Alogliptin/metformin	Sitagliptin/metformin	Linagliptin/metformin
DPP-4 inhibitor	Alogliptin	Sitagliptin	Linagliptin
Metformin dose burden	High	High	High
Dosage form	Immediate-release fixed-dose tablet	Immediate- or extended-release options depending on product	Immediate-release fixed-dose tablet
Key formulation issue	Large tablet and low-dose API uniformity	Dose flexibility and release technology	Tablet size and combination dosing
Differentiation path	Cost, regional access, excipient efficiency	Brand familiarity and broader product history	Renal-dose convenience for linagliptin component
Generic pressure	High where protections have expired	High	High

SGLT2 and GLP-1 products have changed the commercial environment. A low-cost DPP-4/metformin combination remains relevant for patients and health systems prioritizing oral administration, tolerability, and cost, but it has weaker growth prospects than products with cardiovascular, renal, or weight-loss differentiation.

What revenue exposure is associated with alogliptin/metformin?

Standalone revenue exposure is difficult to isolate because manufacturers often report alogliptin, combination products, and geographic sales in aggregated diabetes portfolios. The financial opportunity is therefore better modeled through volume and net price assumptions than through historical brand revenue.

A generic commercial model should stress:

• number of treated patients;
• percentage using DPP-4 inhibitor therapy;
• share receiving a fixed-dose combination;
• available 500 mg and 1,000 mg strengths;
• reimbursement and tender pricing;
• number of competing suppliers;
• manufacturing cost per tablet;
• regulatory launch timing;
• regional substitution rules.

The revenue pool is more attractive in markets with established alogliptin use, limited local competition, and reimbursement for fixed-dose combinations. It is less attractive where sitagliptin, linagliptin, SGLT2 inhibitors, or GLP-1 products dominate prescribing.

Key Takeaways

• Alogliptin/metformin is a conventional immediate-release fixed-dose tablet containing 12.5 mg alogliptin and either 500 mg or 1,000 mg metformin hydrochloride.
• Metformin drives tablet size, compression, dissolution, and patient acceptability challenges.
• Mannitol, povidone, crospovidone, magnesium stearate, and hypromellose provide a practical reference formulation platform.
• The strongest excipient opportunities involve high-functionality mannitol, low-moisture processing, efficient coating, and moisture-barrier packaging.
• Generic formulation design is feasible, but content uniformity, dissolution, stability, and bioequivalence are the principal technical risks.
• The commercial opportunity is primarily generic and regional, with limited prospects for premium pricing absent a meaningful usability or manufacturing advantage.
• Current Orange Book listings, FDA application status, patent certifications, and litigation records control the actual U.S. entry timeline.
• Competitive pressure from other DPP-4/metformin combinations and newer SGLT2 or GLP-1 therapies limits long-term growth.

FAQs

Can alogliptin/metformin be formulated as an extended-release tablet?

Yes, but an extended-release product would be a new formulation requiring separate development, release testing, and regulatory support. It could create tablet-size and dosing advantages, but it would face more complex in vitro and clinical bioequivalence requirements than an immediate-release generic.

Which excipient is most important for the 1,000 mg strength?

The diluent and compression system is most important because the metformin dose dominates tablet mass. Mannitol grade, particle-size distribution, granulation method, and compression behavior can determine whether the tablet is manufacturable at an acceptable size.

Is a co-processed excipient likely to infringe the reference product?

Not necessarily. Co-processed mannitol, microcrystalline cellulose, or disintegrant systems can provide a design-around route, but infringement depends on the claims of the relevant patents, not on the excipient name alone.

Can the alogliptin and metformin doses be adjusted independently?

Not with the fixed-dose tablet. The combination is unsuitable when the clinically required alogliptin or metformin dose does not match the marketed strength. Separate tablets may be necessary, particularly in renal impairment or during metformin titration.

Is alogliptin/metformin a strong candidate for premium excipient pricing?

Usually no. The product is a mature small-molecule combination with a conventional tablet design. Premium excipient pricing is more defensible when the material reduces manufacturing steps, improves stability, enables smaller tablets, or materially increases manufacturing yield.

References

1. U.S. Food and Drug Administration. (n.d.). Kazano (alogliptin benzoate and metformin hydrochloride) tablets: Prescribing information. FDA.
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. FDA.
3. European Medicines Agency. (n.d.). Vipdomet: EPAR product information. EMA.