期刊
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
卷 26, 期 7, 页码 709-728出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10837450.2021.1944207
关键词
In-situ forming implants; PLGA; biodegradable; solvent exchange; PEGylation
Due to low oral bioavailability of certain drugs, there is growing interest in parenteral administration to directly target drug absorption into the blood. Injectable in-situ forming implants (ISFIs) are gaining popularity compared to other sustained release systems, offering easier production, acceptable administration routes, reduced dosing frequency, and improved patient compliance. The use of biodegradable polymers like PLGA in ISFI systems allows for extended drug delivery through solvent exchange mechanisms, with drug release characterized by initial burst, diffusion processes, and polymeric degradation. Suitable solvent selection and consideration of PLGA hydrophobicity and molecular weights are crucial for optimizing drug release in ISFIs.
As a result of the low oral bioavailability of several drugs, there is a renewed interest for parenteral administration to target their absorption directly into the blood bypassing the long gastrointestinal route and hepatic metabolism. In order to address the potential side effects of frequent injections, sustained release systems are the most popular approaches for achieving controlled long-acting drug delivery. Injectable in-situ forming implants (ISFIs) have gained greater popularity in comparison to other sustained systems. Their significant positive aspects are attributed to easier production, acceptable administration route, reduced dosing frequency and patient compliance achievement. ISFI systems, comprising biodegradable polymers such as poly (lactide-co-glycolide) (PLGA) based on solvent exchange mechanisms, are emerged as liquid formulations that develop solid or semisolid depots after injection and deliver drugs over extended periods. The drug release from ISFI systems is generally characterized by an initial burst during the matrix solidification, followed by diffusion processes and finally polymeric degradation and erosion. The choice of suitable solvent with satisfactory viscosity, miscibility and biocompatibility along with considerable PLGA hydrophobicity and molecular weights is fundamental for optimizing the drug release. This overview gives a particular emphasis on evaluations and the wide ranges of requirements needed to achieve reasonable physicochemical characteristics of ISFIs.
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