Detailed Analysis of the Scope and Claims of United States Patent 5,540,930
Introduction
United States Patent 5,540,930, titled "Suspension of Loteprednol Etabonate for Ear, Eye, or Nose Treatment," was granted on July 30, 1996, to inventors Yaacov J. Guy, Doron I. Friedman, and Carmei Yosef, and assigned to Pharmos Corporation. This patent revolves around the formulation and stabilization of aqueous suspensions containing water-insoluble steroid drugs, specifically loteprednol etabonate, for therapeutic use in ophthalmic and otolaryngological treatments.
Background of the Invention
The invention addresses a common issue in pharmaceutical formulations: the instability of aqueous suspensions of water-insoluble drugs. These suspensions often form cakes due to the aggregation of the suspended material, which can be mitigated using polymeric compounds like polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA)[1][4].
Scope of the Invention
The patent provides novel compositions of matter containing water-insoluble steroid drugs suitable for therapeutic use. Specifically, it focuses on stable aqueous suspensions of loteprednol etabonate with particle sizes ranging from 0.1 to 30 microns, preferably between 1-20 microns, and most preferably between 2-10 microns in mean diameter[1][4].
Claims of the Invention
The patent includes several key claims:
- Composition Claims: The invention claims stable aqueous suspensions of water-insoluble steroid drugs, specifically loteprednol etabonate, with defined particle sizes.
- Formulation Claims: It details the use of nonionic polymers (e.g., PVP, PVA, HPMC, dextran) as suspending agents and non-ionic surface-active agents to stabilize the suspensions.
- Preparation Claims: The patent describes the aseptic preparation of these suspensions and the addition of preservatives to prevent microbiological growth.
- Performance Claims: It specifies that the suspensions should remain stable even after extended periods of settling and can be easily resuspended with minimal shaking[1][4].
Components of the Invention
Component (A) - Drug
The primary component is loteprednol etabonate, a water-insoluble steroid drug.
Component (B) - Suspending Agent
Nonionic water-soluble polymers such as PVP, PVA, HPMC, or dextran are used at concentrations between 0.2-2%, preferably 0.4-1.5%, and more preferably 0.4-1%[1][4].
Component (C) - Surface-Active Agent
A non-ionic surfactant acceptable for ophthalmic or otolaryngological use is included to enhance stability.
Component (D) - Tonicity Agents and Preservatives
Optional components include tonicity agents and preservatives like parabens, propyl parabens, thimerosal, chlorbutanol, and benzethonium chlorides to maintain isotonicity and prevent microbial growth[1].
Stability and Suspendibility
The patent emphasizes the stability of the suspensions, ensuring they remain in a suspendible state even after extended periods. The suspendibility is tested by measuring the time required to eliminate visible residue through wrist shaking, with an acceptable time being around 10 seconds[1][4].
Preservation and Microbiological Testing
The suspensions are prepared under aseptic conditions, and the effectiveness of preservatives is evaluated by exposing the preparations to microbiological organisms for four weeks, as per U.S. Pharmacopeia requirements[1].
Patent Landscape
Classification
The patent is classified under various categories, including A61P (Specific Therapeutic Activity of Chemical Compounds or Medicinal Preparations), A61P27/00 (Drugs for disorders of the senses), and A61P27/16 (Otologicals)[4].
Prior Art and Related Patents
The patent references several prior art documents, including U.S. patents related to the formulation of pharmaceutical suspensions and the use of polymeric compounds for stabilization[1][4].
Expiration and Legal Status
The patent expired on October 25, 2003, marking the end of its lifetime[5].
Impact on Pharmaceutical Formulations
This patent has contributed significantly to the development of stable aqueous suspensions for ophthalmic and otolaryngological treatments. The formulation techniques described have been instrumental in overcoming the challenges associated with water-insoluble drugs, ensuring effective and safe therapeutic applications.
Key Takeaways
- The patent provides stable aqueous suspensions of loteprednol etabonate for ophthalmic and otolaryngological treatments.
- It uses nonionic polymers and surface-active agents to stabilize the suspensions.
- The suspensions are prepared under aseptic conditions and include preservatives to prevent microbial growth.
- The patent emphasizes the importance of particle size and suspendibility in pharmaceutical formulations.
FAQs
What is the primary drug component in the patent 5,540,930?
The primary drug component is loteprednol etabonate, a water-insoluble steroid drug.
What are the common suspending agents used in this patent?
Nonionic water-soluble polymers such as PVP, PVA, HPMC, or dextran are used as suspending agents.
Why is the particle size of the drug important in this patent?
The particle size is crucial for ensuring the stability and suspendibility of the aqueous suspension, with preferred sizes ranging from 1-20 microns.
How are the suspensions tested for stability and microbiological safety?
The suspensions are tested for stability by measuring the time required to resuspend the material through wrist shaking, and for microbiological safety by exposing them to various organisms for four weeks as per U.S. Pharmacopeia requirements.
What is the legal status of the patent 5,540,930?
The patent expired on October 25, 2003.
Cited Sources
- United States Patent 5,540,930 - Suspension of Loteprednol Etabonate for Ear, Eye, or Nose Treatment[1].
- Drug Patent Watch - Pharmaceutical drugs covered by patent 5,540,930[2].
- Google Patents - US5540930A - Suspension of Loteprednol Etabonate for Ear, Eye, or Nose Treatment[4].
- FDA Documents - Application Number: 50804 - Zylet Ophthalmic Suspension[5].
