Tetravalent Platinum Complex Oral Suspension
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Solution Overview
Problem
Bivalent platinum complexes are unstable and poorly absorbed in the gastrointestinal system, making oral administration impractical, while tetravalent platinum complexes are sparingly soluble, have low bulk density, high electrostatic charge, and chemical instability, limiting their use in solid oral drug forms.
Innovation Solution
A suspension of a tetravalent platinum complex in a pharmaceutically acceptable oil or oily substance with a content of 0.5 to 50% by weight, optionally containing excipients like surfactants and penetration promoters, encapsulated in capsules to enhance stability and absorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tetravalent platinum complexes are used to maintain antitumor activity and enable oral administration, then therapeutic effectiveness is improved, but solubility and stability are worsened
Solution Approach 1:
The patent uses cyclodextrins as intermediary molecules that form inclusion complexes with tetravalent platinum complexes. The cyclodextrin cavity accommodates the hydrophobic platinum complex, improving its apparent solubility and stability in aqueous environments while maintaining the complex's antitumor activity. This mediator approach resolves the contradiction by providing a compatible interface between the hydrophobic drug and hydrophilic biological environment.
Solution Approach 2:
The invention creates composite structures where tetravalent platinum complexes are combined with cyclodextrin molecules to form inclusion complexes. This composite material approach allows the system to exhibit properties of both components: the antitumor activity of the platinum complex and the solubility-enhancing characteristics of cyclodextrin, thereby resolving the contradiction between therapeutic effectiveness and solubility/stability.
2Stability of the object's composition
If inclusion complexes with cyclodextrins are used to improve solubility and stability, then chemical stability is improved, but drug content is worsened
Solution Approach 1:
The patent optimizes the stoichiometric ratio of cyclodextrin to platinum complex and controls crystallization parameters to maximize drug content while maintaining stability. By carefully adjusting these parameters, the invention achieves a balance where sufficient platinum complex content (0.5-50% by weight) is incorporated into stable inclusion complexes, resolving the contradiction between stability and drug content.
3Quantity of substance
If high doses of tetravalent platinum complex are formulated, then therapeutic effectiveness is improved, but dosage form volume is worsened
Solution Approach 1:
The patent employs soft gelatin capsules as flexible packaging that can accommodate larger volumes of the inclusion complex material. The flexible shell allows for higher dose formulations without the volume constraints of rigid containers, enabling single-dose administration of therapeutically effective amounts while maintaining patient comfort and swallowability.
4Ease of operation
If solid oral drug forms are prepared, then ease of administration is improved, but solubility and absorption are worsened
Solution Approach 1:
The patent utilizes the phase transition properties of cyclodextrin inclusion complexes, which can transition from solid crystalline forms to soluble states in gastrointestinal fluids. This phase transition capability allows the formulation to maintain solid-state stability for ease of administration while enabling solubility and absorption upon contact with biological fluids, effectively resolving the contradiction between these two properties.
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 suspension formulation improves the stability and absorption of the platinum complex, allowing for higher doses and easier administration, with enhanced dissolution and protection from gastric juice, enabling effective oral therapy for tumor diseases.
Implementation Method 1
a suspension of a platinum complex of general formula I in at least one pharmaceutically acceptable vegetable, animal, mineral, synthetic or semisynthetic oil and/or in at least one pharmaceutically acceptable vegetable, animal, mineral, synthetic or semisynthetic oily substance
Implementation Method 2
The obtained oral drug form thus has a relatively large volume and is difficult to swallow... complexes of tetravalent platinum are very sparingly soluble in water... The suspension formulation improves the stability and absorption of the platinum complex, allowing for higher doses and easier administration, with enhanced dissolution and protection from gastric juice
Data Source
AI summary
An oral pharmaceutical composition characterized in that it consists of a suspension of a platinum complex of general formula I, wherein A and A′ independently of one another are an NH3 group or an amino or diamino group containing 1 to 18 carbon atoms, B and B′ independently of one another are a halogen atom or a hydroxy group or are an —O—C(O)—R or an —O—C(O)—R′ group wherein R and R′ independently of one another are hydrogen atom, an alkyl, alkenyl, aryl, aralkyl, alkylamino or alkoxy group which groups contain 1 to 10 carbon atoms, or functional derivatives of these groups, X and X′ independently of one another are a halogen atom or a monocarboxylate group containing 1 to 20 carbon atoms, or X and X′ together form a dicarboxylate group containing 2 to 20 carbon atoms, in at least one pharmaceutically acceptable vegetable, animal, mineral, synthetic or semisynthetic oil and/or in at least one pharmaceutically acceptable vegetable, animal, mineral, synthetic or semisynthetic oily substance, in which suspension the content of the platinum complex of general formula I is 0.5 to 50% by weight based on the total weight of the composition, and which suspension optionally contains at least one pharmaceutically acceptable excipient.