Injectable Depot Compositions for Controlled Drug Release
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Solution Overview
Problem
Current depot formulations for sustained drug delivery, particularly for schizophrenia treatment, face challenges in controlling initial drug release and maintaining therapeutic plasma levels over extended periods, leading to irregular administration and potential adverse events.
Innovation Solution
The development of injectable compositions that form a biodegradable, single-unit implant in situ, using a polymeric matrix with a water-miscible solvent like DMSO, which controls drug release by adjusting viscosity, intrinsic viscosity of the polymer, and water solubility of the drug, ensuring consistent plasma levels for up to 14 days without initial burst release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If conventional depot formulations are used, then extended drug delivery is achieved, but initial burst release occurs and plasma levels fluctuate irregularly
Solution Approach 1:
The patent applies parameter changes by carefully controlling the viscosity of the polymeric solution (0.5-7.0 Pa·s), the intrinsic viscosity of the polymer (0.20-0.50 dl/g), and the water solubility of the drug (less than 2 mg/ml). These parameter optimizations ensure that the composition forms an implant with controlled porosity and degradation rate, achieving stable plasma levels without initial burst release while maintaining extended duration of action up to 14 days and beyond.
2Duration of action of stationary object
If microparticle-based depot formulations are used, then sustained release is achieved, but lag phase occurs requiring supplementary oral therapy
Solution Approach 1:
The patent employs preliminary action by formulating the composition to provide immediate therapeutic effect upon injection. The optimized viscosity and solubility parameters ensure that the drug is readily available for absorption from the injection site, eliminating the lag phase characteristic of microparticle formulations. This allows patients to discontinue oral supplementation immediately after injection while the implant provides sustained release for at least 14 days.
3Duration of action of stationary object
If depot injections are used, then regular drug delivery is achieved, but patient compliance monitoring becomes complex
Solution Approach 1:
The patent applies segmentation by providing a single-unit implantable composition that delivers the entire treatment course in one injection. This eliminates the need for multiple injections or complex administration schedules, simplifying the treatment process and making compliance monitoring straightforward. The single injection provides therapeutic levels for at least 14 days, reducing the burden on both patients and healthcare providers.
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 solution provides stable and controlled drug release profiles from the first day, reducing the need for supplementary oral therapy and minimizing fluctuations in plasma levels, thus improving patient compliance and treatment efficacy while avoiding adverse events.
Implementation Method 1
the composition is defined by certain selected ranges and ratios of viscosity of the polymeric solution, inherent or intrinsic viscosity of the polymer, and water solubility of the active ingredient
Implementation Method 2
controlling at least one of the following parameters of the composition, either alone or in combination: the viscosity of the polymeric solution; the inherent or intrinsic viscosity of the polymer; and the water solubility of the active ingredient
Data Source
AI summary
Injectable depot compositions comprising a biocompatible polymer which is a polymer or copolymer based on lactic acid and/or lactic acid plus glycolic acid having a monomer ratio of lactic to glycolic acid in the range from 48:52 to 100:0, a water-miscible solvent having a dipole moment of about 3.7-4.5 D and a dielectric constant of between 30 and 50, and a drug, were found suitable for forming in-situ biodegradable implants which can evoke therapeutic drug plasma levels from the first day and for at least 14 days.