In vivo characterization of Perseris and compositionally equivalent formulations.

Perseris is asubcutaneous extended-release risperidone in situ forming implant (suspension) indicated for the treatment of adult schizophrenia. Owing to the release rate controlling polymer poly(lactide-co-glycolide) (PLGA), one injection of Perseris can deliver risperidone for one month, which significantly reduces the administration frequency and improves patient compliance. The PLGA and drug used in Perseris was previously identified through reverse engineering and two compositionally equivalent formulations (F-1 and F-2) showing similar in vitro drug release were developed. The current work focuses on in vivo exploration of Perseris and the developed compositionally equivalent formulations using a rabbit model and further evaluate the sameness of the developed formulations compared to Perseris. The in vivo pharmacokinetic (PK) profiles, drug absorption rate, phase separation rate, macro appearance, weight loss as well as the water uptake of the solidified drug depots at different time points were investigated and compared with the in vitro release data as well as with dog and human in vivo data available in literature. Results show that the rabbit PK profile of Perseris was relevant with those obtained from both the dog model and the clinical data, indicating that the rabbit model is appropriate for investigation of the in vivo performance of risperidone implants. Consistent with their similar in vitro drug release, the two compositionally equivalent formulations demonstrated similar PK profiles, drug absorption rates, weight loss and swelling in vivo compared to Perseris. Although the erosion mechanism appeared to be similar between in vitro and in vivo, there were in vitro-in vivo differences concerning the drug release kinetics, phase separation rates and swelling behavior. This work provides a comprehensive in vitro/in vivo understanding of Perseris and the developed compositionally equivalent formulations, which will be beneficial for future development of generic as well as novel PLGA in situ forming implant products.

Reverse engineering of Perseris and development of compositionally equivalent formulations.

Six injectable, long-acting in situ forming implant drug products based on poly(lactide-co-glycolide) (PLGA) and N-Methyl-2-Pyrrolidone (NMP) are available on the market. However, generic products, which would likely be more affordable for patients, are not yet available. This is partially due to the unique complexity of these formulations as well as the inherent heterogeneity of PLGA and the challenges in the manufacture and characterization of this polymer. This article focuses on a comprehensive characterization of Perseris (risperidone) in situ forming implant drug product, and the development of compositionally equivalent formulations. The molecular weight (MW), lactide/glycolide (L/G) ratio, end group, blockiness and glass transition temperature (Tg) of PLGA, as well as the crystal form and particle size of risperidone powder used in Perseris were identified through reverse engineering. The dissolved/suspended drug ratio in the final implant suspension for administration, as well as the real-time drug solid state in the solidified Perseris drug depot were investigated. Two compositionally equivalent formulations prepared using customized PLGA polymers with similar properties to the Perseris PLGA showed similar in vitro release and swelling behavior to Perseris as demonstrated using a novel adapter-based dissolution method. The novelty of this dissolution method lies in its ability to control implant shape, generate reproducible data, distinguish different release phases, as well as identify formulation changes. The knowledge gained in this work and the methodology established for characterization of the implant formulations are important for implant formulation development.

Objective and subjective benefits of a psychiatric pharmacist-led long-acting injectable medication training at a large, multisite organization.

INTRODUCTION: Many psychiatric, long-acting injectable (LAI) medications are available, and each product comes with its own unique challenges. Improper administration can lead to pain, decreased efficacy, and loss of trust in the patient-provider relationship. This study was conducted to determine if a pharmacist-led, 1-hour training was successful in increasing psychiatric LAI medication knowledge through a pretest and posttest. The study also assessed staff satisfaction, confidence, and relevance to practice through a feedback questionnaire. METHODS: Four 1-hour live trainings took place in November 2019. Thirty-five nurses and 8 medical assistants attended 1 of the trainings. A pretest and posttest was administered to determine the training's efficacy, and then a final assessment was administered 4 to 6 weeks after the training. Additionally, a participant feedback questionnaire was given to determine the perceived benefits of the training. RESULTS: The primary outcome was to compare pretest and posttest scores. The pretest average score was 67%, the posttest average score was 97%, and the average score 4 to 6 weeks after the training was 97%. The secondary outcome was to review feedback questionnaires to determine the perceived benefit and effectiveness of the training. Ninety-five percent of participants selected that they were very satisfied with the training, 88% selected they would definitely use the information presented in their work, and 93% selected that they had a lot of confidence in the topic after the training. DISCUSSION: A psychiatric LAI medication training administered to nursing staff and medical assistants improved knowledge scores and was perceived as being useful.