Detailed Analysis of the Scope and Claims of United States Patent 5,286,497
Introduction
United States Patent 5,286,497, titled "Diltiazem formulation," is a significant patent in the pharmaceutical industry, particularly in the development of controlled release formulations for the drug diltiazem hydrochloride. This patent, granted to Andrx Pharmaceuticals, Inc., outlines a novel approach to creating a once-daily oral administration formulation of diltiazem.
Background of the Invention
Diltiazem hydrochloride is a calcium channel blocker used to treat hypertension, angina, and certain heart rhythm disorders. The need for a controlled release formulation arose to maintain therapeutic serum levels and enhance patient compliance by reducing the frequency of dosing[5].
Scope of the Patent
The patent describes a formulation suitable for once-daily administration, comprising a blend of diltiazem beads with different release profiles. Here are the key aspects of the scope:
Controlled Release Profile
The formulation is designed to achieve a specific dissolution profile:
- At least 20% of the diltiazem must be released after 6 hours.
- No more than 50% should be released after 12 hours.
- At least 70% must be released after 24 hours.
- At least 85% must be released after 30 hours[1][4].
Types of Beads
The patent introduces two types of beads:
- Rapid Release Beads: These beads have a lesser amount of coating and release diltiazem quickly.
- Delayed Release Beads: These beads have a greater amount of coating and release diltiazem more slowly[1][4].
Stair-Step Release Profile
The combination of rapid and delayed release beads creates a "stair-step release profile," which ensures a steady and controlled release of diltiazem over an extended period. This profile is crucial for maintaining therapeutic levels of the drug in the bloodstream[5].
Claims of the Patent
The patent claims are centered around the specific formulation and the process of creating the beads:
Formulation Claims
- The patent claims a pharmaceutical formulation containing diltiazem hydrochloride in the form of beads with varying coatings.
- The formulation includes a blend of rapid release and delayed release beads to achieve the desired dissolution profile[1][4].
Process Claims
- The patent describes the process of making the beads, including the application of different amounts of coating to achieve the rapid and delayed release profiles.
- The process involves ensuring that the beads meet specific dissolution requirements to maintain the therapeutic efficacy of the drug[1][4].
Challenges and Improvements
One of the significant challenges with the original formulation described in U.S. Pat. No. 5,286,497 is the difficulty in reliably producing the two types of beads to achieve the required dissolution profile. To address this, subsequent patents introduced the use of three types of beads: rapid release, intermediate release, and delayed release beads. This approach allows for a more flexible and reliable method of achieving the desired release profile without the need for sharp step-like release profiles from individual bead types[1].
Patent Landscape
The patent landscape surrounding U.S. Pat. No. 5,286,497 includes several related patents and formulations:
Related Patents
- U.S. Pat. No. 5,529,791: This patent describes another extended release form of diltiazem using beads coated with a microporous membrane.
- U.S. Pat. No. 5,567,441: This patent discloses a formulation bioequivalent to Cardizem® CD but with a different release profile in hydrochloric acid[2][5].
Commercial Products
- Cardizem® CD: This is a commercially available product based on the formulation described in U.S. Pat. No. 5,286,497.
- TiazacTM/ViazemTM: These are other commercially available extended release formulations of diltiazem hydrochloride[2][5].
Impact on Pharmaceutical Industry
The formulation described in U.S. Pat. No. 5,286,497 has had a significant impact on the pharmaceutical industry:
Patient Compliance
The once-daily administration of diltiazem has improved patient compliance by reducing the number of doses required, thereby enhancing the therapeutic efficacy of the drug[5].
Market Competition
The patent has influenced the development of other extended release formulations of diltiazem, leading to a competitive market with various products offering similar benefits[2].
Key Takeaways
- Controlled Release Profile: The patent achieves a specific dissolution profile through the use of rapid and delayed release beads.
- Stair-Step Release Profile: The combination of beads creates a stair-step release profile, ensuring steady drug release.
- Challenges and Improvements: Subsequent patents introduced three types of beads to improve the reliability of the formulation.
- Patent Landscape: The patent is part of a broader landscape including related patents and commercial products.
- Impact: The formulation has improved patient compliance and influenced the development of other extended release products.
FAQs
What is the main purpose of U.S. Pat. No. 5,286,497?
The main purpose is to describe a controlled release formulation of diltiazem hydrochloride suitable for once-daily oral administration.
What types of beads are used in the formulation?
The formulation uses rapid release beads and delayed release beads to achieve the desired dissolution profile.
What is the "stair-step release profile"?
The "stair-step release profile" is a controlled release profile created by the combination of rapid and delayed release beads, ensuring a steady release of diltiazem over an extended period.
What are some of the challenges associated with this patent?
One of the challenges is the difficulty in reliably producing the two types of beads to achieve the required dissolution profile.
How has this patent impacted the pharmaceutical industry?
It has improved patient compliance by reducing the frequency of dosing and has influenced the development of other extended release formulations of diltiazem.
Sources
- US5968552A - Diltiazem hydrochloride formulation - Google Patents
- US6524620B2 - Diltiazem controlled release formulation and method of manufacture - Google Patents
- Patent Claims and Patent Scope - Hoover Institution
- US5286497A - Diltiazem formulation - Google Patents
- Two pellet controlled release formulation for water soluble drugs - Justia Patents
