US Patent 8,372,431: Eslicarbazepine acetate immediate-release composition with controlled dissolution at pH 4.5
What is the claimed invention in US 8,372,431?
US 8,372,431 claims oral solid and composition formulations built around eslicarbazepine acetate (also referenced as licarbazepine acetate within the claims set), packaged with specific excipient ratios and engineered to achieve measurable dissolution performance under tightly defined test conditions.
Core composition architecture appears in the independent claims as a three-to-four component matrix plus dissolution and physical property constraints:
- Drug: 80 to 90 wt% eslicarbazepine acetate
- Binder: 3 to 10 wt% povidone
- Disintegrant: 3 to 10 wt% croscarmellose sodium
- Lubricant: 0.1 to 3 wt% magnesium stearate
- Performance: dissolution of at least 60% at ~30 min
- Test medium: pH ~4.5
- Apparatus: paddle (USP/Ph. Eur. referenced)
- Temperature: 37 ± 0.5 °C
- Rotation speed: about 100 rpm
Independent claim 8 introduces a two-phase solid structure (intragranular/extragranular), expanding the scope beyond a simple blend by specifying where disintegrant and lubricant reside.
The claim set also includes dependent claim performance upgrades and additional product-related features (flavoring and sweetening agents; tablet/capsule; apparent density ranges; exclusion of fillers/diluents).
What are the independent claims and their exact claim scope?
Claim 1 (pharmaceutical composition with dissolution target)
A pharmaceutical composition with:
| Element |
Requirement |
| Eslicarbazepine acetate |
80–90 wt% |
| Povidone |
3–10 wt% |
| Croscarmellose sodium |
3–10 wt% |
| Magnesium stearate |
0.1–3 wt% |
| Dissolution |
≥60% at ~30 min |
| Medium |
pH ~4.5 |
| Apparatus |
paddle |
| Temperature |
37 ± 0.5 °C |
| Speed |
~100 rpm |
Claim 8 (solid pharmaceutical composition with intragranular/extragranular phases)
A solid pharmaceutical composition comprising:
| Phase |
What it contains |
| Intragranular phase |
l incubazepine acetate (eslicarbazepine acetate per dependent claims 12 and 13) + povidone + croscarmellose sodium |
| Extragranular phase |
croscarmellose sodium + a lubricant |
Material split and composition totals:
| Component |
Constraint |
| Total eslicarbazepine acetate |
80–90 wt% (relative to total solid composition) |
| Total povidone |
3–10 wt% |
| Total croscarmellose sodium |
3–10 wt% and about equally apportioned between intragranular and extragranular phases |
| Lubricant |
0.1–3 wt% |
| Dissolution |
≥60% at ~30 min |
| Medium/Apparatus/Temp/Speed |
pH ~4.5, paddle, 37 ± 0.5 °C, ~100 rpm |
Claim 5/6/7 (composition with flavoring and/or sweetening agents)
Claims 5, 6, and 7 extend Claim 1’s composition with at least one flavoring agent and/or sweetening agent, while preserving the same dissolution requirement (≥60% at ~30 min, pH ~4.5, paddle, 37 ± 0.5 °C, ~100 rpm).
How tight are the performance limitations (dissolution and pH)?
The claim set locks dissolution outcomes to specific dissolution test conditions.
Dissolution thresholds by claim tier
The scope is tiered in dependent claims:
| Dissolution claim tier |
Minimum dissolution at ~30 min |
Claim numbers (examples from provided set) |
| Baseline |
≥60% |
1, 8, and many dependent variants |
| Higher |
≥65% |
16, 17, 18, 19, 20, etc. |
| Higher |
≥67.9% |
21, 22, 23, 39, 40, 41, 42, 43, etc. |
| Average across multiple dosage forms |
≥70% average |
24–28 |
| Dissolution + average metric |
≥50% dissolution and ≥65% average |
29–34 |
| Lower dissolution + average metric |
≥40% dissolution and ≥65% average |
34–38 |
Test specification embedded in claims
- Medium pH: “about 4.5”
- Temperature: “37 ± 0.5 °C”
- Apparatus: “paddle apparatus”
- Speed: “about 100 rpm”
- Time: “about 30 minutes”
- Some dependent claims explicitly reference standards:
- Ph. Eur. edn 6, 2.9.3 or USP 21, <711> (claims 39–43)
This reduces design-around paths because the claim ties dissolution performance to conventional pharmacopeial paddle testing.
How broad is the excipient scope?
Quantitative excipient windows are wide, but constrained by dissolution
The following are explicitly quantized:
- Eslicarbazepine acetate: 80–90 wt%
- Povidone: 3–10 wt%
- Croscarmellose sodium: 3–10 wt%
- Lubricant: 0.1–3 wt% magnesium stearate
Within that, dependent claims add structure-specific placement rules.
Lubricant identity is broadened in Claim 8’s dependent claims
For the two-phase solid, Claim 8’s lubricant can be:
| Claim |
Lubricant option |
| 9 |
magnesium stearate |
| 10 |
sodium lauryl sulphate |
| 11 |
combination of magnesium stearate + sodium lauryl sulphate |
This matters for freedom-to-operate because the “lubricant” concept is not limited to magnesium stearate in the phase-structured embodiment.
Where does the disintegrant sit? Intragranular vs extragranular
Claim 8 hardwires the distribution of croscarmellose sodium:
- About equally apportioned between intragranular and extragranular phases.
Dependent claims 2–4 refine this across the simpler formulation framework:
- Claim 2: eslicarbazepine acetate is intragranular
- Claim 3: half of croscarmellose sodium intragranular; half extragranular
- Claim 4: magnesium stearate is extragranular
These are high-value constraints because distribution is often a processing artifact, and changing distribution can change dissolution.
What additional product attributes are claimed?
Flavor and sweetening
- Claim 5: adds flavoring agents to the Claim 1 matrix
- Claim 6: adds sweetening agents
- Claim 7: adds both
Form factor
- Claim 83: composition is a tablet or capsule
- Claim 84–86: solid pharmaceutical composition is a tablet or capsule
Apparent density constraints (process sensitivity proxy)
Claims 44–86 introduce apparent density limitations across multiple dependency ladders:
| Apparent density band |
Claim group examples |
| 0.5–1.5 g/mL |
44–70, 51–70 etc. |
| 0.6–1.4 g/mL |
71–74, 72–74 etc. |
| 0.7–1.3 g/mL |
75–77 |
| 0.8–1.1 g/mL |
78–80 |
Exclusion of filler/diluent
- Claim 81: solid composition comprises no filler or diluent (for solid claims 82 on the corresponding intragranular framework)
This narrows formulation work because conventional direct compression or wet granulation often uses diluents.
How does the claim set handle “licarbazepine acetate” vs “eslicarbazepine acetate”?
Within the provided claim text:
- The independent structural claim 8 uses “licarbazepine acetate”
- Dependent claims 12–15 map:
- “wherein the licarbazepine acetate is eslicarbazepine acetate” (claims 12–15)
So the operative drug identity is eslicarbazepine acetate when the dependent mapping is invoked.
Claim-by-claim enforcement leverage (what is hardest to design around?)
Highest-risk design parameters
The most enforcement-relevant elements are those that are both:
1) explicit in wt%/ratio, and
2) tied to measured performance.
Those include:
- dissolution thresholds (≥60%, ≥65%, ≥67.9%, and average metrics)
- dissolution test conditions (pH ~4.5, paddle, 37 ± 0.5 °C, ~100 rpm, ~30 min)
- intragranular/extragranular distribution requirements in Claim 8 (especially croscarmellose split and lubricant phase)
Moderate-risk parameters
- apparent density bands: often measurable and may be tied to manufacturing settings
- “no filler or diluent”: eliminates common formulation relief valves
Lower-risk parameters
- flavor/sweetening: likely additive features that still need to maintain dissolution performance but can be compensated for.
Patent landscape framing for US 8,372,431 (scope-level)
You requested a “patent landscape” analysis, but no additional citation set was provided beyond the claims you pasted. Without the bibliographic record of US 8,372,431 (assignee, filing date, priority claims, continuation/divisional family members, cited art, and prosecution history), a complete competitive landscape cannot be produced without inventing sources.
What can be done from the claim text alone is to map the likely technology neighborhood and where landscape disputes usually concentrate:
Technology neighborhood
The claim scope is anchored in:
- eslicarbazepine acetate oral solid formulation
- pH 4.5 dissolution performance, using paddle apparatus
- granulation-engineered placement (intragranular/extragranular disintegrant and lubricant positioning)
- controlled excipient ratios (povidone/croscarmellose/magnesium stearate)
Where competitors typically overlap
In an eslicarbazepine formulation patent landscape, overlap usually occurs in:
- reformulations that adjust disintegrant levels or distribution to improve dissolution
- alternate lubricants or blends, particularly those affecting tablet/capsule performance
- managing dissolution in acidic conditions (pH ~4.5)
Where design-arounds typically focus
From the claim language provided, practical design-around targets would be:
- changing formulation sufficiently to drop below the dissolution threshold under the same test conditions
- changing excipient placement such that intragranular/extragranular allocation no longer satisfies “about equally apportioned” constraints
- selecting lubricant systems that violate the specific lubricant options for the phase-structured claim
- altering physical characteristics like apparent density outside the claimed bands
- incorporating fillers/diluents if “no filler or diluent” is invoked
Key Takeaways
- US 8,372,431 claims eslicarbazepine acetate oral solid formulations with strict quantitative excipient windows and pharmacopeial-style dissolution performance at pH ~4.5 using a paddle at ~100 rpm and 37 ± 0.5 °C after ~30 minutes.
- The independent claim set has two main enforcement structures:
1) a straightforward wt% composition (Claim 1) with ≥60% dissolution, and
2) a two-phase intragranular/extragranular architecture with about-equal croscarmellose split and specified lubricant placement (Claim 8).
- Dependent claims materially expand scope through:
- improved dissolution thresholds (≥65%, ≥67.9%) and average metrics across multiple dosage forms,
- optional flavoring and/or sweetening agents,
- explicit apparent density bands,
- optional lubricant choices in the phase-structured embodiment (magnesium stearate; sodium lauryl sulphate; or both),
- and exclusions like “no filler or diluent.”
- A true “patent landscape” requires bibliographic and citation data beyond the claim text; the claims provided nonetheless pinpoint the exact technical axes where competitive overlap and freedom-to-operate disputes are likely to cluster.
FAQs
1) What is the central performance metric in US 8,372,431?
Dissolution of at least 60% at about 30 minutes in pH ~4.5 using a paddle apparatus at 37 ± 0.5 °C and about 100 rpm.
2) Does the patent cover only magnesium stearate as lubricant?
Claim 1 uses magnesium stearate (0.1–3 wt%). Claim 8’s phase-structured embodiment allows lubricant being magnesium stearate, sodium lauryl sulphate, or a combination (dependent claims 9–11).
3) Is croscarmellose sodium placement required?
Yes for the phase-structured embodiment: Claim 8 requires croscarmellose sodium to be about equally apportioned between intragranular and extragranular phases.
4) What dissolution test standards are referenced?
Dependent claims cite Ph. Eur. edn 6, 2.9.3 and USP 21, <711> for paddle dissolution measurement (claims 39–43 in the provided text).
5) What manufacturing-adjacent physical property is claimed?
The set includes apparent density ranges (e.g., 0.5–1.5 g/mL, 0.6–1.4 g/mL, 0.7–1.3 g/mL, 0.8–1.1 g/mL) depending on the dependent claim.
References
[1] US Patent 8,372,431, claims text as provided by user (no bibliographic record supplied).
