Controlled Release Formulations via Salt Solubility and Emulsion

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Solution Overview

Problem

Current controlled release compositions face challenges in producing high drug load formulations with minimal burst effect and bioactive agent degradation, leading to inefficient manufacturing processes and undesirable release profiles.

Innovation Solution

A method involving combining a bioactive agent and a polymer in an organic phase with an organic ion in an aqueous phase, followed by an emulsion process to create controlled release compositions, which includes using specific solvents, cosolvents, and emulsifying agents to enhance encapsulation efficiency and reduce degradation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If highly water soluble bioactive agents are used, then solubility is improved, but burst effect increases and treatment effectiveness decreases

Engineering Contradiction:
Improvesolubility of bioactive agentVSAvoidtreatment effectiveness
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent changes the chemical parameter of the bioactive agent by converting it to a less water-soluble salt form (e.g., sodium salt to hydrochloride salt or organic acid salt). This parameter change reduces water solubility while maintaining or enhancing therapeutic effectiveness, thereby eliminating the burst effect and improving treatment reliability.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If organic acids are combined with bioactive agent to produce water insoluble addition salt, then burst effect is reduced, but manufacturing complexity increases

Engineering Contradiction:
Improveburst effect controlVSAvoidmanufacturing procedure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges the salt formation step with the encapsulation process by directly combining the bioactive agent with the polymer in the organic phase during formulation preparation. This integration eliminates separate purification and drying steps, reducing manufacturing complexity while maintaining burst effect control through the use of less water-soluble salt forms.

Inventive Principle:
Principle #5Merging (Combining)

3Ease of manufacture

If acetate salt of bioactive agent is encapsulated, then encapsulation is simplified, but chemical degradation increases

Engineering Contradiction:
Improveencapsulation simplicityVSAvoidbioactive agent stability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent changes the salt form parameter from acetate salt to alternative salts such as hydrochloride salts or salts of organic acids with pKa values between 3-7. This parameter change reduces chemical degradation and improves bioactive agent stability during encapsulation and storage, while maintaining manufacturing simplicity through direct incorporation into the organic phase.

Inventive Principle:
Principle #35Parameter changes

4Quantity of substance

If large injection volume is used to achieve high drug load, then drug loading is improved, but patient comfort decreases

Engineering Contradiction:
Improvedrug loadVSAvoidpatient comfort
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The patent changes the solubility parameter of the bioactive agent by using less water-soluble salt forms, which enables higher drug loading concentrations in the organic phase. This allows formulation of controlled release compositions with high drug load that require smaller injection volumes, thereby improving patient comfort while maintaining high therapeutic dosage.

Inventive Principle:
Principle #35Parameter changes

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 method achieves increased drug load, reduced bioactive agent degradation, and consistent release profiles, improving the effectiveness and efficiency of controlled release formulations.

Implementation Method 1

an effective quantity of an organic ion leaves the aqueous phase and enters the organic phase

Methodology Applied
Scientific EffectPhase transfer:

Implementation Method 2

contacting the resulting organic and aqueous phases to produce a controlled release composition through an emulsion process

Methodology Applied
Scientific EffectEmulsion: Emulsion

Data Source

PatentUS8871269B2Method for the preparation of controlled release formulations
Publication Date: 2014.10.28 EVONIK CORPORATION

AI summary

The methods disclosed herein are of use for the production of controlled release compositions. In particular, the methods provide the contacting of an organic phase containing a bioactive agent and a polymer with an aqueous phase containing an organic ion to create controlled release compositions containing bioactive agents. The present invention also includes controlled release compositions including a polymer, an organic ion and a bioactive agent. The present invention also includes methods of using such controlled release compositions. The usefulness of the present invention is that the methods result in the production of controlled release compositions containing bioactive agent capable of administration in a concentrated low-dose form, having low burst and reduced production of degraded bioactive agent.