United States Patent 5,360,615: A Detailed Analysis of Scope, Claims, and Patent Landscape
Introduction
United States Patent 5,360,615, titled "Solvent system enhancing the solubility of pharmaceuticals for encapsulation," is a significant invention in the field of pharmaceutical formulation. This patent, granted in 1994, addresses the critical issue of enhancing the solubility of pharmaceutical agents, which is crucial for their effective encapsulation and delivery.
Background and Motivation
The solubility of pharmaceutical agents is a major challenge in the development of drug formulations. Many drugs, especially those that are acidic, basic, or amphoteric, have limited solubility in common solvents, making it difficult to achieve high concentrations necessary for effective dosing. This patent aims to overcome this hurdle by introducing a novel solvent system.
Key Claims and Inventions
Solvent System Composition
The patent describes a solvent system designed to enhance the solubility of pharmaceutical agents. This system typically includes a combination of polyethylene glycol (PEG) and a hydroxide ion source, such as sodium hydroxide. The addition of glycerin or polyvinylpyrrolidone (PVP) further enhances the solubility of the pharmaceutical agent[1].
Mechanism of Action
The solvent system works by forming the ionized form of the acidic or basic pharmaceutical agent, which is then solvated by the system. For acidic agents, the use of sodium hydroxide increases the ionization, thereby enhancing solubility. For basic agents, the presence of hydrogen ions achieves a similar effect, making the agent soluble even at lower temperatures[1].
Specific Pharmaceutical Agents
The patent highlights several pharmaceutical agents that benefit from this solvent system, including cimetidine, ranitidine, and nifedipine for basic agents, and thioridazine as an example of a basic drug that becomes soluble in PEG 400 with the addition of hydrogen ions[1].
Scope of the Patent
Applicability to Various Formulations
The solvent system is versatile and can be used for various pharmaceutical formulations, including soft gel encapsulation, tablets, and other dosage forms. This broad applicability makes the patent significant in the pharmaceutical industry[1].
Stability and Concentration
The invention ensures not only increased solubility but also stability and higher concentrations of the pharmaceutical agent in the solvent system. This is crucial for maintaining the efficacy and shelf life of the drug product[1].
Patent Landscape and Related Inventions
Prior Art and Comparisons
The patent builds upon prior art, such as the use of small amounts of PVP or glycerin to hasten dissolution of micronized digoxin in a liquid vehicle, as described in U.S. Pat. No. 4,002,718. However, the current invention introduces a more comprehensive and effective solvent system for a wider range of pharmaceutical agents[1].
Similar Patents and Formulations
Other patents, such as CA2690488A1, focus on specific formulations like naproxen for soft gel encapsulation, using similar principles of enhancing solubility through the use of hydroxide ions and polyethylene glycol. These patents collectively contribute to the advancement of pharmaceutical formulation technology[4].
Impact on Pharmaceutical Industry
Enhanced Bioavailability
The increased solubility achieved by this solvent system directly translates to better bioavailability of the pharmaceutical agents. This is a critical factor in ensuring the efficacy of drugs, as higher bioavailability means that more of the active ingredient is available to the body[1].
Cost and Efficiency
By enabling the formation of highly concentrated solutions, this invention can reduce the size of dosage units, such as soft gel capsules, making them more convenient and cost-effective to produce and administer[1].
Legal and Regulatory Considerations
Patent Eligibility
The patent falls under the category of "composition of matter" as defined by Section 101 of the Patent Act, making it eligible for patent protection. The claims are specific and directed towards a practical application, avoiding abstract ideas or natural processes that might be ineligible under current patent eligibility standards[5].
Expiration and Public Domain
As the patent has expired, the technology is now in the public domain, allowing other manufacturers to use and build upon this invention without infringing on the original patent rights.
Industry Expert Insights
Industry experts emphasize the importance of such inventions in overcoming the solubility challenges that are common in drug development. For example, Dr. John Gardella, in his work related to U.S. Pat. No. 4,002,718, highlights the significance of using solubility-enhancing agents to improve drug formulations[1].
Statistics and Examples
- Solubility Enhancement: The use of sodium hydroxide can increase the solubility of acidic pharmaceutical agents by several orders of magnitude, as demonstrated in the patent's examples.
- Practical Applications: The formulation of thioridazine, which was insoluble in PEG 400 at room temperature, becomes soluble even at -5°C with the addition of hydrogen ions[1].
Key Takeaways
- Solvent System: The patent introduces a novel solvent system using PEG and hydroxide ions to enhance the solubility of pharmaceutical agents.
- Broad Applicability: The invention is applicable to various pharmaceutical formulations, including soft gels and tablets.
- Stability and Concentration: The system ensures higher concentrations and stability of the pharmaceutical agents.
- Industry Impact: The invention has significantly improved the bioavailability and convenience of drug formulations.
- Legal Status: The patent has expired, making the technology publicly available.
FAQs
Q: What is the main purpose of the solvent system described in US Patent 5,360,615?
A: The main purpose is to enhance the solubility of pharmaceutical agents, particularly those that are acidic, basic, or amphoteric, to facilitate their encapsulation and delivery.
Q: How does the solvent system work?
A: The system works by forming the ionized form of the pharmaceutical agent using a hydroxide ion source, such as sodium hydroxide, and solvating it with polyethylene glycol (PEG).
Q: What are some examples of pharmaceutical agents that benefit from this solvent system?
A: Examples include cimetidine, ranitidine, nifedipine, and thioridazine.
Q: Is the technology described in this patent still under patent protection?
A: No, the patent has expired, and the technology is now in the public domain.
Q: How does this invention impact the pharmaceutical industry?
A: It enhances the bioavailability of drugs, reduces the size of dosage units, and improves the efficiency and cost-effectiveness of drug production.
Sources
- US5360615A - Solvent system enhancing the solubility of pharmaceuticals for encapsulation - Google Patents
- Patent Claims Research Dataset - USPTO
- Patent Claims and Patent Scope - Hoover Institution
- CA2690488A1 - Pharmaceutical formulations of naproxen for soft gel encapsulation and combinations thereof - Google Patents
- Patent-Eligible Subject Matter Reform: An Overview - CRS Reports
