Details for Patent: 5,932,247

Executive summary
US Patent 5,932,247 claims a tightly defined solid oral dosage formulation and manufacture for a compound of a specific structural formula (X = 0 to 5, including optical isomers). The patent’s core claim scope is (i) an excipient system (croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch, gelatin, magnesium stearate), (ii) a manufacturing sequence that includes gelatin-in-water addition, drying and milling, and post-addition of croscarmellose sodium, and (iii) two hard performance benchmarks for tablet dissolution in USP Apparatus 2 within 45 minutes in either water (37°C, 50 rpm) or 0.001 N HCl (37°C, 50 rpm). The numeric excipient percentages in dependent claims and the dissolution threshold “not less than 75% of label” constrain infringement risk for generic or reformulated products, and they set clear design-around levers: excipient substitution outside the claimed ratios, removal/variation of gelatin step, changes to the croscarmellose sodium handling sequence, or failure to meet the dissolution criterion under the specified test conditions.

What is the scope of US Patent 5,932,247 (solid unit dosage, gelatin blend, croscarmellose, USP Apparatus 2 dissolution)

US 5,932,247 is directed to a pharmaceutical composition in solid unit dosage form made for a specific drug substance class defined by “a compound of the formula: ##STR10## wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof.”

What the patent claims at a high level

The claim set is formulation-focused and process-integration-focused:

1. Claim 1 (capsules, process steps, excipient set)

   • Solid unit dosage form: filled into capsules.
   • Process: blend the formula compound with microcrystalline cellulose + lactose + pregelatinized starch, then add a gelatin solution in water, mix, dry and mill, then add croscarmellose sodium with mixing, then fill into capsules.

2. Claims 2–4 (tablets, excipient percentages, dissolution performance)

   • Pressed into tablets from blends containing specific excipient amounts by weight.
   • Performance: dissolution under USP Apparatus 2:
     • Claim 2: in water, 37°C, 50 rpm, 45 minutes, and dissolution of drug substance must be ≥ 75% of label.
     • Claim 3: in 0.001 N aqueous HCl, 37°C, 50 rpm, 45 minutes, and dissolution ≥ 75%.
     • Claim 4: in 0.001 N aqueous HCl, 37°C, 50 rpm, 45 minutes, and dissolution ≥ 75%, with a different excipient percentage profile (and notably excludes lactose in that dependent claim).

Claim coverage boundaries that matter for infringement

Because the claims require both composition features and (in dependent claims) testable dissolution performance, infringement is functionally limited to products that match the excipient system and meet the dissolution criteria under the specified apparatus and conditions.

What are the exact claim elements in US 5,932,247 Claim 1 (capsule formulation process)

Claim 1 has three layers: (A) the active definition, (B) the excipient composition used in blending, and (C) the process sequence.

A. Active ingredient scope

• The drug substance is “a compound of the formula” with:
  • X = 0 to 5
  • includes individual optical isomers
    This language can broaden coverage across multiple analogs (different X values) and specific stereoisomers as long as they fall within the structural definition.

B. Composition/excipient elements required

Claim 1 requires the formula compound blended with:

• microcrystalline cellulose
• lactose
• pregelatinized starch

Claim 1 also requires later addition of:

• croscarmellose sodium
• and a process that includes gelatin added as a solution in water (gelatin is not listed as a fixed percentage in Claim 1).

Claim 1 does not explicitly require magnesium stearate in Claim 1, though later dependent claims include it.

C. Process sequence required for Claim 1

Claim 1 requires a process with these steps in substance:

1. Blend active + microcrystalline cellulose + lactose + pregelatinized starch
2. Add gelatin solution in water and mix
3. Dry and mill the mixture
4. Add croscarmellose sodium with mixing
5. Fill the resulting mixture into capsules

Infringement implication: A capsule product that uses a different binder system than gelatin, or that performs dissimilar granulation steps (for example, without gelatin solution, or without drying and milling before croscarmellose addition), is a potential design-around candidate because Claim 1 reads on a specific manufacturing sequence.

How do Claims 2–4 narrow scope (tablet ratios plus USP Apparatus 2 dissolution)

Claims 2–4 each constrain:

• formulation excipient weight percentages,
• unit form: pressed tablets,
• dissolution performance threshold: ≥ 75% of label within 45 minutes,
• dissolution medium and conditions: water or 0.001 N HCl at 37°C, 50 rpm using USP Apparatus 2.

Claim 2: tablet composition ratios + dissolution in water

Required excipient amounts by weight:

• croscarmellose sodium: 4.8%
• microcrystalline cellulose: 33.7%
• lactose: 33.7%
• pregelatinized starch: 9.6%
• gelatin: 3.5%
• magnesium stearate: 0.5%

Performance requirement:

• dissolution in water
• 45 minutes
• USP Apparatus 2 conditions: 37°C, 50 rpm
• drug dissolved: not less than 75% of label

Infringement implication: Even small changes to excipient percentages (e.g., changing magnesium stearate from 0.5% to 0.75%) or reformulating to shift dissolution below 75% under these exact conditions can reduce infringement risk.

Claim 3: tablet composition ratios + dissolution in 0.001 N HCl

Required excipient amounts by weight:

• croscarmellose sodium: 4.8%
• microcrystalline cellulose: 25.7%
• lactose: 25.7%
• pregelatinized starch: 9.6%
• gelatin: 3.5%
• magnesium stearate: 0.75%

Performance requirement:

• dissolution in 0.001 N aqueous hydrochloric acid
• 45 minutes, USP Apparatus 2: 37°C, 50 rpm
• ≥ 75% of label

Infringement implication: This claim expressly allows lactose and requires gelatin; changing the base carrier (e.g., removing lactose, replacing gelatin, or using alternative disintegrants) is likely outside the literal ratios.

Claim 4: tablet composition ratios + dissolution in 0.001 N HCl (no lactose)

Required excipient amounts by weight:

• croscarmellose sodium: 6%
• microcrystalline cellulose: 33.3%
• pregelatinized starch: 30%
• magnesium stearate: 0.75%

Performance requirement:

• dissolution in 0.001 N aqueous hydrochloric acid
• 45 minutes, USP Apparatus 2: 37°C, 50 rpm
• ≥ 75% of label

Notable scope change vs Claims 2–3:

• Claim 4 lists croscarmellose sodium, microcrystalline cellulose, pregelatinized starch, magnesium stearate only; it does not mention lactose or gelatin in the recited excipient list (though other unrecited excipients could still be present without violating the claim only if the claim language is interpreted to require only those listed amounts as “present in amounts of about…”).

Infringement implication: A tablet with a binder/disintegrant system that relies on lactose or gelatin may still fall within Claim 4 if the required listed excipients and ratios are met and the performance benchmark is achieved. Conversely, a lactose-free formulation could be engineered to match the Claim 4 percentages and still risk infringement if dissolution is ≥75%.

What does “not less than 75% of label in 45 minutes using USP Apparatus 2” do to claim scope

The performance benchmark is a gating requirement in Claims 2–4.

What is explicitly claimed

• “quantity of compound … dissolved in 45 minutes”
• “not less than 75% of label”
• dissolution media:
  • Claim 2: water
  • Claims 3–4: 0.001 N aqueous hydrochloric acid
• apparatus/conditions:
  • USP Apparatus 2
  • 37° C. and 50 rpm

How performance constraints affect infringement and design-around

A generic applicant can potentially reduce risk by:

• failing to meet the dissolution threshold in the specified medium and conditions,
• shifting dissolution kinetics by modifying the formulation (and therefore granulation/disintegration behavior),
• using excipient systems outside the claimed weight percentages.

Because “≥ 75%” is objective and measured, a product that scores below 75% can be positioned as non-infringing for those dependent claims, even if the excipient set partially overlaps.

How broad is the drug substance definition (X = 0 to 5 and optical isomers)

The active definition “wherein X is a number ranging from about zero to 5, and the individual optical isomers thereof” expands scope in two dimensions:

1. Structural genus over X
   Coverage spans multiple structural variants (X values from ~0 to 5). The “about” qualifier can broaden further around boundary values.

2. Stereochemical coverage
   “individual optical isomers” suggests the claims cover not only a specific stereoisomer but the stereoisomeric variants falling under the same chemical formula definition.

Infringement implication: Products that use different X values or different stereoisomers could still be covered if they fit the defined structural template.

How does the excipient system functionally drive dissolution and disintegration

Across the claims, the recurring components are:

• croscarmellose sodium: superdisintegrant driving tablet disintegration
• microcrystalline cellulose: filler/binder supporting mechanical integrity and porosity
• lactose (Claims 1–3, Claim 2–3): soluble filler affecting dissolution rate
• pregelatinized starch: disintegrant/binder affecting wetting and gel behavior
• gelatin: binder used as gelatin solution and, in Claims 2–3, present as a weight % in final blends
• magnesium stearate: lubricant affecting hydrophobicity and dissolution

The patent’s combination of disintegrant (croscarmellose, pregelatinized starch), soluble filler (lactose in certain claims), and a binder system (gelatin in Claim 1 and Claims 2–3) is tied to the dissolution outcomes.

What patent landscape analysis can be performed from the provided claim text alone

Only the claims themselves are provided; no patent family data, prosecution history, citing references, priority dates, or claim construction record is included. Under those constraints, the only defensible landscape analysis is a scope map to likely infringement and design-around outcomes based strictly on claim elements.

Likely infringement targets (based on literal overlap)

• Capsules produced using the Claim 1 process: gelatin-in-water addition, drying and milling, then post-addition of croscarmellose sodium, with lactose and pregelatinized starch plus microcrystalline cellulose as the blend carriers.
• Tablets whose excipient percentages match Claims 2–4 “about” ranges and that also meet the ≥75% dissolution within 45 minutes under the exact medium/app settings.

Likely design-around levers

• Remove or replace gelatin (especially for Claim 1 and for Claims 2–3 which require gelatin at 3.5%).
• Alter excipient percentages (Claim 2’s magnesium stearate 0.5% vs Claim 3’s 0.75%; Claim 4’s croscarmellose 6% and pregelatinized starch 30%).
• Change dissolution behavior under USP Apparatus 2: tuning lubrication level, porosity, particle size distribution, and disintegrant hydration behavior can be used to fall below 75% in the specified media.
• Change granulation workflow: for Claim 1, the order of gelatin addition and the drying/milling step plus when croscarmellose is introduced is explicitly claimed.

**Is US 5,932,247 primarily composition or method-of-manufacture?

It is both, but the method aspects are limited to the manufacturing process recited in Claim 1, not a broader process claim set.

• Claim 1 is a product-by-process-style formulation claim for capsules: it ties the capsule mixture to a defined blending and granulation sequence.
• Claims 2–4 are composition + performance claims for tablets: the process is not recited as a manufacturing sequence; instead, the claims tether infringement to the excipient composition and the in vitro dissolution outcome.

How strong is the claim estate for litigation on formulation and dissolution

Based solely on the provided claim text, the strength is rooted in three litigation-friendly features:

1. Objective dissolution benchmark
   USP Apparatus 2 with explicit conditions and a defined threshold provides a measurable standard.

2. Tight excipient ratio recitations in dependent claims
   Claims 2 and 3 lock in multiple excipient percentages simultaneously, reducing interpretive flexibility.

3. Explicit process steps in Claim 1
   The gelatin solution, drying and milling, and post-addition of croscarmellose are concrete steps that can be tested via manufacturing records.

The main vulnerability is that a defendant can design around by not meeting one element (e.g., excipient ratios, gelatin presence, dissolution threshold, or process sequencing), and the independent capsule/process claim is narrower to the defined unit operation (capsules) and recited process.

Key takeaways

• US 5,932,247 claims a defined solid oral formulation for a compound of a structural genus (X = 0 to 5, optical isomers).
• Claim 1 covers a capsule process: blend with microcrystalline cellulose/lactose/pregelatinized starch, add gelatin in water, then dry and mill, then add croscarmellose sodium, and fill capsules.
• Claims 2–4 cover tablets with hard numeric excipient percentages and a dissolution gate: ≥75% of label in 45 minutes using USP Apparatus 2 at 37°C/50 rpm, in water (Claim 2) or 0.001 N HCl (Claims 3–4).
• The strongest design-around levers are excipient ratio changes, binder/disintegrant substitutions that alter dissolution behavior, and disruption of gelatin/croscarmellose handling sequence (especially for capsule manufacturing).
• Performance-based constraints can be used to argue non-infringement if dissolution falls below the claimed threshold under the specified test conditions.

FAQs

1. Does US 5,932,247 require the tablet to dissolve at least 75% in water or only in 0.001 N HCl?
Claim 2 requires ≥75% in water; Claims 3 and 4 require ≥75% in 0.001 N aqueous HCl.

2. What is the USP dissolution setup specified in the claims?
USP Apparatus 2 at 37°C and 50 rpm, with dissolution measured at 45 minutes.

3. Which claims include gelatin as a required excipient?
Claim 1 requires a gelatin solution in water as part of the process. Claims 2 and 3 recite gelatin at 3.5% by weight. Claim 4 does not list gelatin.

4. Is lactose mandatory across all tablet claims?
No. Lactose is recited in Claims 2 and 3 but not listed in Claim 4.

5. Can a product avoid infringement by using a different lubricant level (magnesium stearate)?
In Claims 2 and 3, magnesium stearate is fixed at 0.5% (Claim 2) or 0.75% (Claim 3). Changing to a different level can move the product outside the claimed excipient percentages, assuming the “about” boundaries are not met.

References

1. US Patent 5,932,247, “Pharmaceutical composition in solid unit dosage form,” claims 1–4 (as provided in prompt).