United States Patent 5,997,903: A Comprehensive Analysis
Overview of the Patent
United States Patent 5,997,903, assigned to Byk Gulden, pertains to oral delayed release tablet dosage forms of pantoprazole, a proton pump inhibitor used to treat conditions such as gastroesophageal reflux disease (GERD), ulcers, and Zollinger-Ellison syndrome. This patent is crucial in the pharmaceutical industry due to its innovative formulation techniques that overcome the stability and release challenges associated with pantoprazole.
Key Components of the Patent
Active Compound and Formulation
The patent describes an orally administrable medicament in pellet or tablet form, with pantoprazole as the active compound. This compound is often used in its salt form, such as pantoprazole sodium sesquihydrate, to enhance stability and bioavailability[1][4].
Core Composition
The core of the tablet consists of pantoprazole or its physiologically tolerated salt, mixed with a binder (e.g., polyvinylpyrrolidone (PVP) and/or hydroxypropylmethylcellulose (HPMC)), a filler (e.g., mannitol), and optionally other tablet auxiliaries or basic physiologically tolerated inorganic compounds[1].
Intermediate Layer
An inert water-soluble intermediate layer surrounds the core. This layer includes a polymer like HPMC and plasticizers such as PVP and propylene glycol. This layer is critical for protecting the core from gastric juice and ensuring the tablet's integrity[1].
Enteric Coating
The outer layer is an enteric coating, typically a copolymer of methacrylate/acrylic acid, which prevents the release of pantoprazole in the acidic environment of the stomach. This coating ensures that the drug is released in the more alkaline environment of the intestine, where it can be effectively absorbed[1].
Manufacturing Process
The patent outlines a detailed process for preparing these tablets, which includes:
- Granulation: The active compound and excipients are mixed and granulated.
- Intermediate Finishing: The granulated mixture is combined with spray-dried mannitol and other excipients.
- Compression: The mixture is compressed into cores.
- First Coating (Insulating Layer): The cores are coated with the intermediate layer.
- Second Coating (Enteric Layer): The cores are then coated with the enteric layer[1].
Pharmaceutical Technical Attributes
The formulation described in the patent ensures several key pharmaceutical attributes:
- Stability: The use of selected binders and fillers prevents stability issues of the active ingredient.
- Hardness and Friability: The tablet cores have adequate hardness (approximately 40N to 60N) and low friability (approximately 0.1% to 0.7%), making them suitable for coating without chipping or breaking[1].
- Release Profile: The enteric coating ensures that pantoprazole is released in the intestine, avoiding degradation in the stomach.
Patent Claims and Scope
The patent claims cover the specific formulation and manufacturing process of pantoprazole tablets. Key claims include:
- The composition of the core, intermediate layer, and enteric coating.
- The process of granulation, compression, and coating.
- The specific excipients and their proportions used in the formulation[1].
Impact on the Pharmaceutical Industry
This patent has significantly influenced the development of pantoprazole formulations. It addresses critical challenges such as stability and release profile, making pantoprazole a viable treatment option for various gastrointestinal conditions.
Comparison with Other Patents
Other patents, such as US7838027B2, also describe multiparticulate formulations of pantoprazole but with different approaches. For example, US7838027B2 focuses on multiparticulate compositions that avoid higher amounts of disintegrants and surfactants to achieve desired pharmaceutical attributes[2][4].
Litigation and Legal Landscape
The patent has been involved in various legal proceedings, highlighting its importance in the pharmaceutical industry. For instance, it has been referenced in cases related to patent infringement and validity[5].
Conclusion
United States Patent 5,997,903 is a landmark patent in the field of pharmaceuticals, particularly for proton pump inhibitors like pantoprazole. Its innovative formulation and manufacturing process have set a standard for ensuring the stability and effective release of pantoprazole, making it a crucial component in the treatment of various gastrointestinal disorders.
Key Takeaways
- Innovative Formulation: The patent describes a unique formulation of pantoprazole that includes a core, an intermediate layer, and an enteric coating.
- Manufacturing Process: The process involves granulation, compression, and two coating steps.
- Pharmaceutical Attributes: The formulation ensures stability, adequate hardness, and low friability, along with a controlled release profile.
- Industry Impact: The patent has significantly influenced the development of pantoprazole formulations.
- Legal Significance: The patent has been involved in various legal proceedings related to patent infringement and validity.
Frequently Asked Questions (FAQs)
1. What is the main challenge addressed by this patent?
The main challenge addressed by this patent is the stability and controlled release of pantoprazole in the gastrointestinal tract.
2. What are the key components of the pantoprazole tablet formulation?
The key components include the core (pantoprazole or its salt, binder, filler), an intermediate water-soluble layer, and an outer enteric coating.
3. How is the tablet manufactured according to the patent?
The manufacturing process includes granulation, intermediate finishing, compression, and two coating steps (insulating and enteric coating).
4. What are the pharmaceutical technical attributes ensured by this formulation?
The formulation ensures stability, adequate hardness, low friability, and a controlled release profile.
5. How does this patent compare to other pantoprazole formulation patents?
This patent focuses on a specific tablet formulation, whereas other patents like US7838027B2 describe multiparticulate compositions with different approaches to excipient use.
