Ophthalmic Formulation Stabilizing Three Active Ingredients
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Solution Overview
Problem
Current ophthalmic formulations for treating ocular hypertension lack a stable combination of Dorzolamide Hydrochloride, Timolol Maleate, and Brimonidine Tartrate, with existing excipients not ensuring chemical stability and compatibility among active ingredients.
Innovation Solution
A novel ophthalmic formulation incorporating Polyoxyl 40 stearate, Sodium Borate crystals, Sodium chloride, Benzalkonium chloride, and optional Mannitol, Hydroxypropyl-beta-cyclodextrines, and Sodium Hyaluronate as excipients to achieve physiological compatibility and stability, with specific quantitative ratios optimizing the coexistence of active principles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a combination of Dorzolamide Hydrochloride, Timolol Maleate and Brimonidine Tartrate is used to treat ocular hypertension, then therapeutic effectiveness is improved, but chemical stability and compatibility among active ingredients deteriorates
Solution Approach 1:
The patent introduces specific excipients as intermediary substances to mediate between the three active ingredients. Mannitol acts as a stabilizing agent that prevents degradation, while Sodium Borate and Boric Acid serve as buffer agents to maintain pH balance, preventing chemical reactions between the active ingredients. These intermediary substances enable the combination therapy to remain chemically stable while retaining therapeutic effectiveness.
Solution Approach 2:
The patent optimizes specific parameter values including pH (adjusted to 7.0-7.4 using borate buffer), osmolarity (adjusted to 280-320 mOsm/kg using Mannitol and Sodium Chloride), and concentrations of each active ingredient. By carefully controlling these parameters, the formulation achieves both chemical stability and therapeutic effectiveness simultaneously.
2Ease of manufacture
If conventional excipients are used in ophthalmic formulations, then ease of manufacture is improved, but compatibility and stability among multiple active ingredients deteriorates
Solution Approach 1:
The patent creates a composite excipient system combining Mannitol, Sodium Borate, Boric Acid, Sodium Chloride, and Benzalkonium Chloride in specific proportions. This composite approach provides multiple functions simultaneously: Mannitol for stability and osmolarity adjustment, borate buffer for pH control, Sodium Chloride for tonicity, and Benzalkonium Chloride for preservation. The composite material approach simplifies manufacturing while ensuring compatibility among the three active ingredients.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The formulation demonstrates enhanced chemical stability and reduced stinging, maintaining effective concentrations of active ingredients over three months, with Formula F2 showing optimal stability and minimal irritation.
Implementation Method 1
The combination of Boric Acid and Sodium Borate possesses good buffering ability and is commonly used in ophthalmic preparations as pH buffers.
Implementation Method 2
Mannitol is mainly used in pharmaceutical preparations as a diluent in tablets and in liquid solutions to adjust the osmolarity.
Implementation Method 3
Sodium Chloride is widely used in a variety of parenteral and non-parenteral pharmaceutical formulations, where the principle purpose is to produce isotonic solutions.
Implementation Method 4
Polyoxyl 40 stearate is generally used as an emulsifier in oily/water type creams and lotions.
Implementation Method 5
Benzalkonium chloride is a component of quaternary ammonium which is used in pharmaceutical formulations as a preservative in similar applications to other cationic surfactant agents such as Cetrimide.
Data Source
AI summary
The present invention is related to ophthalmic formulations for the treatment of ocular ailments. More specifically, it is related to the pharmaceutical industry in the production of ophthalmic medication for the treatment of ocular hypertension. The advantage of the present invention over other state of the art treatments is that it achieves a composition of Dorzolamide Hydrochloride, Timolol Maleate and Brimonidine Tartrate with excellent properties of stability; it does not give rise to chemical reactions which produce modifications in the active molecules; with no antagonistic effects among the components. The present invention consists of a stable pharmaceutical composition for the treatment of ocular hypertension characterized by consisting of the following excipients: Polyoxyl 40 Stearate, Sodium Borate crystals, Sodium Chloride, Mannitol and Benzalkonium chloride.