Pasireotide Depot Formulation With Phase-Change Controlled Release
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Solution Overview
Problem
Existing peptide-based drug delivery systems face challenges such as high degradation in biological fluids, limited bioavailability, discomfort during administration due to wide needles, irritant degradation products, burst/lag release profiles, complex manufacturing, and limited drug load, which are particularly problematic for somatostatin analogues like Pasireotide.
Innovation Solution
A pre-formulation comprising diacyl glycerol, phosphatidyl choline, biocompatible organic mono-alcoholic solvent, and polar solvent, optimized to form a low viscosity phase that transitions into a controlled release depot upon exposure to aqueous fluids, allowing easy administration through narrow needles and providing a stable, non-burst release profile.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptide-based drug delivery systems are used, then therapeutic effects can be achieved, but high degradation in biological fluids occurs leading to limited bioavailability
Solution Approach 1:
The patent applies preliminary action by pre-formulating the peptide with protective excipients (phospholipids, proteins, or polymers) before administration. This pre-protection mechanism shields the peptide from enzymatic degradation in biological fluids, maintaining its integrity and bioavailability throughout the desired release period.
2Duration of action of moving object
If conventional depot systems are used, then controlled release can be achieved, but burst/lag release profiles occur
Solution Approach 1:
The patent employs parameter changes by carefully controlling the formulation composition ratios, pH, and physical state of the depot system. These parameter adjustments enable a steady-state release profile that eliminates burst and lag phases, providing consistent therapeutic levels throughout the dosing interval.
3Quantity of substance
If wide needles are used for administration, then sufficient drug load can be delivered, but discomfort and pain increase
Solution Approach 1:
The patent utilizes flexible, biodegradable polymer matrices that can be formulated into low-viscosity suspensions or solutions. This flexibility allows the formulation to be administered through narrow, fine-gauge needles while maintaining sufficient drug load capacity, thereby reducing administration discomfort and pain.
4Duration of action of moving object
If polymer microspheres are used, then controlled release is achieved, but irritant degradation products are generated
Solution Approach 1:
The patent changes the chemical composition parameters of the depot system by selecting biodegradable polymers with favorable degradation profiles. These polymers break down into non-irritant, biocompatible products, eliminating local irritation while maintaining the desired controlled release duration.
5Quantity of substance
If high drug load is achieved, then therapeutic efficacy is improved, but formulation complexity increases
Solution Approach 1:
The patent employs composite materials by combining the peptide with excipients such as phospholipids, proteins, or biodegradable polymers in a single integrated formulation system. This composite approach achieves high drug load capacity while simplifying the overall formulation structure and manufacturing process.
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 enables easy and less painful administration, supports high bioactive agent loading, reduces irritation, and achieves a stable plasma concentration of Pasireotide, minimizing peak concentrations and maintaining therapeutic levels for extended periods.
Implementation Method 1
which undergo phase transition upon exposure to aqueous fluids, such as body fluids, thereby forming a controlled release composition
Data Source
AI summary
The present invention relates to compositions forming a low viscosity mixture of:a) 20-50 wt. % of at least one diacyl glycerol;b) 20-54 wt. % of at least one phosphatidyl choline (PC);c) 5-15 wt. % of at least one biocompatible, organic mono-alcoholic solvent;d) 1 to 20 wt. % polar solvente) 5 to 150 mg/ml of at least one peptide somatostatin receptor agonist comprising pasireotide;f) optionally at least one antioxidant;wherein the ratio of components a:b is in the range 40:60 to 54:46; wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with excess aqueous fluid.The invention further relates to methods of treatment comprising administration of such compositions, and to pre-filled administration devices and kits containing the formulations.