Understanding drug release mechanisms of risperidone in situ forming implant depots in rabbits

Understanding Drug Release Mechanisms of Risperidone In Situ Forming Implant Depots in Rabbits


In recent years, the demand for long-acting drug delivery systems has grown significantly, particularly in the treatment of psychiatric disorders such as schizophrenia. Risperidone, a widely prescribed atypical antipsychotic, is often administered in sustained-release formulations to improve patient adherence and maintain therapeutic plasma levels. One promising approach in this field is the use of in situ forming implants (ISFIs)—injectable, biodegradable systems that solidify upon administration and slowly release the drug over time.


In preclinical research, rabbits serve as a valuable model for evaluating the pharmacokinetics and release behavior of such drug delivery systems. Their relatively large body size and subcutaneous space allow for easy implantation and reliable sampling, making them ideal for studying the in vivo performance of ISFIs.


The in situ forming depot for risperidone typically involves dissolving the drug in a biocompatible solvent along with a polymer such as poly(lactic-co-glycolic acid) (PLGA). Upon injection, the solvent diffuses into surrounding tissues, causing the polymer to precipitate and form a solid matrix. This matrix controls the release of risperidone through a combination of diffusion, polymer degradation, and drug partitioning mechanisms.


Several factors influence the release rate, including the polymer concentration, molecular weight, and drug loading, as well as the site of injection. Studies in rabbits have shown a biphasic release pattern—an initial burst followed by a sustained release phase over weeks. By analyzing blood plasma levels and implant residues, researchers can better understand how formulation variables affect drug kinetics.


These findings are crucial not only for optimizing risperidone delivery but also for advancing the broader field of injectable implants. Ultimately, such innovations aim to offer more effective, patient-friendly treatments that reduce dosing frequency and enhance therapeutic outcomes in mental health care.

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