US Patent 6,348,216: Scope, Claims, Expiration and Patent Landscape for Ibuprofen-Hydrocodone Tablets

US Patent 6,348,216 protects a specific immediate-release tablet architecture combining ibuprofen and hydrocodone bitartrate in a wet-granulated, lactose-free and polyvinylpyrrolidone-free formulation. Its core limitations concern excipient selection, ingredient concentration, granulation structure, phase distribution, and compression performance. The patent issued on February 19, 2002, and its ordinary 20-year term ran from the 1999 nonprovisional filing date, producing an estimated expiration date of September 10, 2019, absent applicable patent-term adjustment or extension. It is no longer an enforceable patent right.

What does US Patent 6,348,216 protect?

The patent protects pharmaceutical tablets containing ibuprofen and hydrocodone bitartrate, particularly formulations corresponding to the Vicoprofen product platform. The commercial product contains 200 mg of ibuprofen and 7.5 mg of hydrocodone bitartrate per tablet.

The patent does not broadly claim every ibuprofen-hydrocodone tablet. Its claims require a defined manufacturing process and a narrow excipient system:

Ibuprofen
Hydrocodone bitartrate
Colloidal silicon dioxide
Microcrystalline cellulose or powdered cellulose
A disintegrant
Starch
An alkylhydroxy methylcellulose binder in the narrower claims
A lubricant, generally magnesium stearate
Wet granulation
A tablet substantially free of lactose and polyvinylpyrrolidone
Specific concentration ranges in the principal composition claims
A granule containing both active ingredients in a single phase

The claimed formulation is designed to improve powder flow, tablet compression and disintegration consistency over a broad range of compression forces.

What are the independent claims in US 6,348,216?

The principal independent claims are claims 1, 2 and 34.

Claim	Claim type	Principal limitations	Commercial significance
1	Product and process-linked composition claim	Wet-granulated ibuprofen and hydrocodone; colloidal silicon dioxide; cellulose filler; disintegrant; starch; extra-granular lubricant; lactose- and PVP-free; single-phase active ingredients	Broadest structural claim, but includes several process and functional limitations
2	Quantitative composition claim	Ibuprofen 25%-63%; hydrocodone 0.6%-3.8%; colloidal silicon dioxide 0.5%-3%; filler 10%-42%; disintegrant 4%-10%; binder 2% to less than 6%; starch 11%-20%; lubricant below 1%	Core formulation claim with measurable composition ranges
34	Specific formulation claim	50% ibuprofen; 1.88% hydrocodone bitartrate; 1.5% colloidal silicon dioxide; 19.3% microcrystalline cellulose; 8% croscarmellose sodium; 3.25% HPMC; 15.6% corn starch; 0.5% magnesium stearate	Narrowest and most formulation-specific claim; closely tracks an example composition

Claims 3 through 33 depend principally from claim 2 and narrow the ranges for filler, disintegrant, colloidal silicon dioxide, binder and starch.

How broad is claim 1?

Claim 1 is broad in ingredient selection but narrow in formulation architecture.

It requires the tablet to contain a granule formed by wet granulation. The granule must contain:

Ibuprofen;
Hydrocodone bitartrate;
Colloidal silicon dioxide;
Microcrystalline cellulose or powdered cellulose;
A disintegrant; and
Starch.

The claim also requires the ibuprofen and hydrocodone bitartrate to be in a “single phase” within the granule. The composition must include an extra-granular lubricant, and the ibuprofen, hydrocodone and lubricant must be present in a single phase in the finished tablet.

The functional limitations require that the composition:

Flows well;
Has good compression performance; and
Can be compressed over a wider range of compression forces without a substantial change in disintegration time.

These limitations could create claim-construction issues. “Flows well,” “good compression performance,” “wider range,” and “no substantial change” are not self-defining chemical parameters. Their interpretation would likely depend on the specification, examples, testing methods and expert evidence.

What quantitative ranges does claim 2 require?

Claim 2 imposes a cumulative composition profile. A potentially infringing formulation would need to satisfy all of the following limitations:

Component	Claimed range
Ibuprofen	About 25%-63% by tablet weight
Hydrocodone bitartrate	About 0.6%-3.8%
Colloidal silicon dioxide	About 0.5%-3%
Cellulose filler	About 10%-42%
Disintegrant	About 4%-10%
Alkylhydroxy methylcellulose binder	About 2% to less than 6%
Starch	About 11%-20%
Lubricant	Less than 1%

The granule itself must contain the two active ingredients, colloidal silicon dioxide, filler, disintegrant and starch. The extra-granular material comprises the remaining tablet components.

A formulation outside one or more of these ranges may avoid literal infringement of claim 2, although it could still require analysis against claim 1, claim 34, the doctrine of equivalents, or other patents.

What formulation is claimed by claim 34?

Claim 34 is directed to a specific composition:

Ingredient	Percentage of tablet
Ibuprofen	About 50%
Hydrocodone bitartrate	About 1.88%
Colloidal silicon dioxide	About 1.5%
Microcrystalline cellulose	About 19.3%
Sodium croscarmellose	About 8%
Hydroxypropyl methylcellulose	About 3.25%
Corn starch	About 15.6%
Magnesium stearate	About 0.5%

The granule portion contains approximately:

50% ibuprofen;
1.9% hydrocodone bitartrate;
0.75% colloidal silicon dioxide;
9.5% microcrystalline cellulose;
4% croscarmellose sodium;
10.6% corn starch; and
3.3% hydroxypropyl methylcellulose.

Claim 34 is easier to evaluate analytically because it identifies a concrete formula. It is also easier to design around by changing the active ratio, filler, binder, disintegrant, starch level, lubricant or granulation arrangement.

Are claims 18 through 33 internally consistent?

The supplied claim text contains a material drafting inconsistency.

Claim 2 requires starch at about 11%-20% of the tablet composition. Claims 18 through 33 depend from claim 2, directly or through intervening dependent claims, but recite starch at about 6%-8%. A dependent claim ordinarily incorporates all limitations of the parent claim while adding further limitations. A starch range of 6%-8% does not fall within the parent range of 11%-20%.

This creates at least three possible interpretations:

The 6%-8% range was intended to describe starch within the granule rather than total tablet starch;
The 11%-20% range in claim 2 contains a drafting error; or
The dependent claims are internally inconsistent and vulnerable to an indefiniteness or scope dispute.

The specification and prosecution history would be necessary to determine whether the claims can be harmonized. The inconsistency materially reduces the practical value of relying on claims 18 through 33 without reviewing the intrinsic record.

What manufacturing process does the patent require?

The patent is directed to wet granulation rather than a formulation independent of manufacturing method.

The claimed process architecture is:

Combine ibuprofen and hydrocodone bitartrate with selected excipients;
Form a wet granulated material;
Maintain both active ingredients in the same granule or phase;
Add extra-granular material, including lubricant;
Compress the blend into tablets.

The patent distinguishes this arrangement from formulations in which one active ingredient is separately granulated, added after granulation, or distributed in a separate phase.

This limitation creates potential design-around options. A competing product could use direct compression, dry granulation, roller compaction, separate granulation of the active ingredients, or a formulation in which the lubricant is incorporated differently. Each option would require a full claim-by-claim analysis because the patent includes overlapping independent claims.

What excipients are protected?

The excipient limitations are central to the patent.

Filler

The filler must be microcrystalline cellulose or powdered cellulose. A formulation using dibasic calcium phosphate, mannitol, sorbitol, lactose or another filler could avoid the express filler limitation, subject to equivalents analysis.

Disintegrant

Claim 2 identifies:

Croscarmellose sodium;
Crospovidone; or
Sodium starch glycolate.

The patent is substantially free of polyvinylpyrrolidone. This distinction matters because crospovidone is a cross-linked form of polyvinylpyrrolidone, while the claim language may raise a technical question regarding whether “substantially free of polyvinylpyrrolidone” excludes crospovidone. The specification and prosecution history would control the analysis.

Binder

The binder is an alkylhydroxy methylcellulose, with hydroxypropyl methylcellulose identified in claim 34. The principal range is 2% to less than 6%, with narrower dependent claims reciting approximately 3%-4%.

Lubricant

The lubricant is present below 1% in claim 2. Claim 34 specifies approximately 0.5% magnesium stearate.

Starch

Starch is required in both the broad and narrow composition claims. Claim 34 specifies corn starch at approximately 15.6% of the finished tablet and approximately 10.6% in the granule.

What patent protects Vicoprofen and ibuprofen-hydrocodone tablets?

US Patent 6,348,216 is the key formulation patent associated with the ibuprofen-hydrocodone tablet technology described in the claims. The associated FDA product is Vicoprofen, an immediate-release tablet containing 200 mg ibuprofen and 7.5 mg hydrocodone bitartrate.

The patent does not protect:

Ibuprofen as an active ingredient;
Hydrocodone as an active ingredient;
The general medical use of combining an NSAID with an opioid;
Every ibuprofen-hydrocodone dosage form;
Injectable, liquid or capsule formulations; or
Every manufacturing process for the combination.

Its protection is formulation-specific and depends on the claimed excipient system and granulation structure.

What was the Orange Book status of US 6,348,216?

The patent was historically associated with the FDA-listed Vicoprofen product. The Orange Book framework permits listing patents that claim the drug substance, drug product, formulation or approved method of use. US 6,348,216 is a drug-product formulation patent rather than a basic active-ingredient patent.

Item	Assessment
Reference product	Vicoprofen
Active ingredients	Ibuprofen and hydrocodone bitartrate
Dosage form	Immediate-release tablet
Patent category	Drug-product formulation
Historical patent number	US 6,348,216
Estimated ordinary expiration	September 10, 2019
Current enforceability	Expired
Current Orange Book blocking effect	None from this patent after expiration

The FDA Orange Book should be consulted for the historical listing record, approved product applications and any associated patent-use-code history. An expired formulation patent cannot support a current patent-infringement suit or a present Paragraph IV barrier.

When did US Patent 6,348,216 expire?

The patent issued on February 19, 2002. Based on the September 10, 1999 filing date, its ordinary 20-year term ended on September 10, 2019, subject to any patent-term adjustment or extension reflected in the official USPTO record.

No current exclusivity remains under the patent. Any historical pediatric exclusivity, regulatory exclusivity or patent-term extension would have ended no later than the expiration of the applicable statutory period. The patent is therefore relevant to historical generic-entry analysis, not to current freedom-to-operate as an active patent right.

Were there Paragraph IV challenges to the patent?

An ANDA applicant challenging an Orange Book-listed patent could file a Paragraph IV certification alleging that the patent was invalid, unenforceable or not infringed. A Paragraph IV notice historically could have triggered a 30-month stay under the Hatch-Waxman Act if the NDA holder filed suit within the statutory period.

Because US 6,348,216 has expired, a current Paragraph IV challenge to this patent has no commercial blocking value. Any historical Paragraph IV litigation would be relevant to understanding generic launch timing, settlement terms and market entry, but it would not revive the expired patent.

The supplied information does not identify a specific challenger, notice letter, district-court docket or settlement agreement. A definitive list of challenging companies and litigation outcomes cannot be established from the patent claims alone.

What generic entry risks exist today?

The patent itself creates no current generic-entry barrier. The principal risks now are regulatory, commercial and product-specific:

Whether the proposed generic matches the reference product’s release characteristics;
Whether the applicant can demonstrate bioequivalence;
Whether hydrocodone scheduling requirements affect manufacturing and distribution;
Whether another unexpired patent covers a particular formulation, manufacturing process or method of use;
Whether the proposed labeling creates an induced-infringement issue under an unexpired method-of-use patent; and
Whether controlled-substance quota, supply-chain and DEA compliance requirements affect launch execution.

A generic manufacturer can generally avoid the expired patent through formulation selection, manufacturing process selection or both. The expired patent remains useful as a technical map of the reference product but not as an enforceable exclusionary right.

How can a competitor design around the patent?

Potential design-around variables include:

Design-around variable	Possible approach
Granulation	Direct compression, dry granulation or separate granulation
Phase distribution	Place one active ingredient outside the principal granule
Filler	Use a non-cellulose filler
Disintegrant	Use a different disintegrant or a different level
Binder	Use a binder outside the claimed chemical class or range
Starch	Use a level outside the claimed range
Lubricant	Use a different lubricant or a different concentration
Lactose/PVP limitation	Use lactose or conventional PVP, if compatible with product performance
Active ratio	Change ibuprofen or hydrocodone concentration
Dosage form	Use a capsule, liquid, multiparticulate or another dosage form

These strategies are no longer needed to avoid US 6,348,216 as an enforceable patent. They remain relevant when assessing historical infringement, freedom-to-operate opinions based on the patent’s former term, or related continuation and foreign rights.

How strong was the patent estate?

The patent had moderate technical specificity and limited breadth.

Strengths

It claimed a commercially relevant ibuprofen-hydrocodone tablet architecture.
It identified measurable ingredient ranges.
It tied the active ingredients to a common wet-granulated phase.
It covered a specific formulation that appears aligned with the reference product.
Claims 2 and 34 provided relatively concrete infringement tests.

Weaknesses

Several functional terms are potentially subjective.
The single-phase requirement may require substantial technical evidence.
The process limitation could exclude alternative manufacturing routes.
The dependent-claim starch ranges appear inconsistent with claim 2.
The claim set is vulnerable to design-around through excipient substitution or process changes.
The patent has expired.

The commercial value of the estate was therefore highest before 2019. Its residual value is historical and technical rather than exclusionary.

Does biosimilar risk apply to this patent?

No. Biosimilar risk does not apply because Vicoprofen is a small-molecule drug product, not a biologic. The relevant competitive pathway is an ANDA for a generic ibuprofen-hydrocodone tablet, not a 351(k) biosimilar application.

The competitive issues involve bioequivalence, formulation sameness or permissible differences, controlled-substance compliance and patent certification.

What licensing deals and settlements affect the patent?

The claims alone do not establish a license, covenant not to sue, supply agreement or Paragraph IV settlement. A patent document identifies inventorship, ownership and prosecution history, but it does not prove downstream licensing arrangements.

Any historical commercial agreement would need to be confirmed through:

SEC filings by the patent owner or licensee;
FDA litigation records;
Federal district-court dockets;
Federal Circuit opinions;
FTC or Department of Justice materials; or
ANDA settlement disclosures where available.

No licensing or settlement right can be inferred from US 6,348,216 itself.

Key Takeaways

US 6,348,216 is a formulation patent for wet-granulated ibuprofen-hydrocodone tablets.
The core formulation is lactose-free and substantially free of polyvinylpyrrolidone.
The patent requires specific excipients, concentration ranges and phase relationships.
Claims 1, 2 and 34 are the principal independent claims.
Claim 34 closely tracks a formulation containing 50% ibuprofen and 1.88% hydrocodone bitartrate.
Claims 18 through 33 contain an apparent inconsistency between the 11%-20% starch range in claim 2 and the 6%-8% starch range in the dependent claims.
The patent’s ordinary term expired on or about September 10, 2019.
It no longer creates a current Orange Book or Paragraph IV barrier.
The product is a small-molecule drug, so biosimilar analysis is not applicable.
Current competition is governed by generic approval, bioequivalence, controlled-substance regulation and any later unexpired patent rights.

FAQs About US Patent 6,348,216

What drug is associated with US Patent 6,348,216?

The patent is associated with ibuprofen-hydrocodone immediate-release tablets, commercially represented by Vicoprofen, containing 200 mg ibuprofen and 7.5 mg hydrocodone bitartrate.

Does US 6,348,216 cover all hydrocodone and ibuprofen combinations?

No. It covers a particular tablet formulation and manufacturing architecture. A product using different excipients, concentrations, phase distribution or granulation technology may fall outside the claims.

Is US Patent 6,348,216 still enforceable?

No. Its ordinary patent term expired in 2019 based on the 1999 nonprovisional filing date.

Is Vicoprofen subject to biosimilar competition?

No. Vicoprofen is a small-molecule drug. Competition proceeds through generic-drug pathways, principally ANDAs.

What is the most important technical limitation in the patent?

The most important limitation is the combination of wet granulation, common-phase ibuprofen and hydrocodone bitartrate, specified excipients, and a lactose- and PVP-free tablet composition.

References

U.S. Patent No. 6,348,216. (2002). Pharmaceutical composition comprising ibuprofen and hydrocodone. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. FDA.
U.S. Food and Drug Administration. (1997). Vicoprofen prescribing information. FDA.
Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585.

Details for Patent: 6,348,216

Summary for Patent: 6,348,216