Related Experiment Video
Updated: Jun 26, 2026
12:48
PLGA Nanoparticles Formed by Single- or Double-emulsion with Vitamin E-TPGS
Published on: December 27, 2013
Injectable in situ forming depot systems: PEG-DAE as novel solvent for improved PLGA storage stability
K Schoenhammer1, H Petersen, F Guethlein
1Novartis Pharma AG, Technical Research and Development, 4056 Basel, Switzerland.
International Journal of Pharmaceutics
|January 13, 2009
Summary
Injectable in situ forming depots require stable liquid formulations. Alkylated poly(ethyleneglycol) (PEG-DAE) significantly improved poly(D,L-lactide-co-glycolide) (PLGA) stability in liquid formulations compared to conventional PEG.
Area of Science:
- Polymer chemistry and materials science
- Drug delivery systems
- Biocompatible excipients
Background:
- Injectable in situ forming depots (ISFD) are promising for peptide/protein delivery.
- Liquid storage stability of polymers like poly(D,L-lactide-co-glycolide) (PLGA) in solvents such as poly(ethyleneglycol) (PEG) is critical for ISFD.
- Uncontrolled degradation impacts the efficacy and safety of ISFD.
Purpose of the Study:
- To investigate the degradation of PLGA in PEG solutions.
- To evaluate the impact of temperature and water content on PLGA degradation.
- To assess the stabilizing effect of modified PEG derivatives on PLGA.
Main Methods:
- Polymer molecular weight (Mw) determination using gel permeation chromatography (GPC).
- Monitoring PLGA degradation via Nuclear Magnetic Resonance (NMR) spectroscopy.
- Comparative analysis of PLGA degradation in conventional PEG versus poly(ethyleneglycol) dialkylether (PEG-DAE).
Main Results:
- Conventional PEG solvent caused rapid PLGA degradation (75% Mw loss) at 25°C due to transesterification.
- Alkylated PEG (PEG-DAE) significantly enhanced PLGA stability, with only 3% Mw loss.
- PLGA degradation in PEG-DAE was insensitive to 1% added water, confirming its stability.
- PEG-DAE prevented PEG-PLGA block copolymer formation, unlike PEG300.
Conclusions:
- Transesterification between PEG hydroxy endgroups and PLGA is a primary degradation pathway.
- PEG-DAE is a superior excipient for maintaining PLGA stability in liquid ISFD formulations.
- PEG-DAE offers at least 2 months of PLGA stability, crucial for parenteral ISFD development.
More Related Videos
Related Concept Videos
01:28Parenteral Drug Delivery Systems: Injectables, Implants, and Infusion Devices
Parenteral drug delivery systems play a crucial role in modern therapeutics by enabling the direct administration of drugs into the systemic circulation, bypassing the gastrointestinal tract. These systems are particularly valuable for poorly absorbed oral medications that are unstable in the digestive environment or require rapid onset or sustained therapeutic levels. Delivery is achieved through intravenous, intramuscular, or subcutaneous routes, each selected based on the drug's properties...
01:19Modified-Release Drug Delivery Systems: Rate-Programmed II
Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
01:05Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
01:11Oral Drug Delivery Systems: Delayed-Release Systems
Delayed-release drug delivery systems are specialized pharmaceutical formulations designed to postpone the release of active compounds until the drug reaches a specific region of the gastrointestinal (GI) tract, typically the intestine. These systems are essential for drugs that may cause gastric irritation, are unstable in acidic environments, or need to exert therapeutic effects locally in the intestinal or colonic regions.The core feature of delayed-release systems is the use of enteric...
01:22Modified-Release Drug Delivery Systems: Rate-Programmed I
Rate-programmed drug delivery systems (DDS) are designed to release drugs at specific, controlled rates to maintain consistent therapeutic levels. These systems are categorized based on their release mechanisms, including dissolution-controlled DDS, diffusion-controlled DDS, and combined dissolution-diffusion-controlled DDS.In dissolution-controlled DDS, the release rate depends on the slow dissolution of the drug itself or the surrounding matrix. Drugs with inherently slow dissolution rates,...
01:21Intrauterine Drug Delivery Systems
Controlled-release systems for intravaginal and intrauterine drug delivery have been developed primarily for the administration of contraceptive steroid hormones. These delivery routes circumvent first-pass hepatic metabolism, thereby enhancing bioavailability and allowing for reduced systemic dosages compared to oral administration. Such approaches contribute to improved therapeutic efficacy and patient compliance, particularly in long-term contraceptive regimens.Intravaginal Drug Delivery...