TY - JOUR
T1 - Novel adapter method for in vitro release testing of in situ forming implants
AU - Wang, Xiaoyi
AU - Bao, Quanying
AU - Suh, Min Sung
AU - Kastellorizios, Michail
AU - Wang, Ruifeng
AU - Burgess, Diane J.
N1 - Funding Information:
This work was financially supported through the Pfizer Distinguished Chair of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Connecticut. USP Apparatus 2 and 4 instrument support from Sotax Corporation is highly appreciated.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/6/10
Y1 - 2022/6/10
N2 - In situ forming implants are injectable liquid formulations which form solid or semisolid depots following injection. This allows for minimally invasive administration, localized drug delivery, and extended drug release. Unfortunately, this drug delivery strategy lacks standardized in vitro dissolution methods due to the difficulties in recreating implant formation in vitro that is biomimicry and with reproducible and controllable shape and dimensions. In the present study, an innovative, adapter-based in vitro release testing method was developed to solve this problem. Two distinctively different in situ forming implants (a risperidone formulation (suspension) consisting of PLGA dissolved in N-methyl pyrrolidone (NMP), where risperidone powder was suspended to form a drug suspension, and a naproxen formulation (solution) consisting of PLGA dissolved in NMP, where naproxen was completely dissolved to form a solution), were used as model in situ-forming implants. The results revealed that the implants formed in the custom-designed adapter with a water-dissolvable polyvinyl alcohol (PVA) film were bio-mimicking and reproducible in both shape and burst release of drug according to rabbit data. For both the suspension and solution formulations, this adapter-based in vitro release testing method resulted in consistent release data. Compared with a direct injection in vitro release testing method, the release profiles generated using the adapter-based method were capable of distinguishing the different release phases (initial release within 24 h, diffusion-facilitated release, and degradation-controlled release). In addition, the adapter-based method could discriminate formulation and dissolution apparatus changes and could be utilized to develop accelerated release testing methods. This adapter-based method has the promise of wide use in release testing of in situ forming implant formulations and has the potential to be used in the development of in vivo-predictive in vitro release methods.
AB - In situ forming implants are injectable liquid formulations which form solid or semisolid depots following injection. This allows for minimally invasive administration, localized drug delivery, and extended drug release. Unfortunately, this drug delivery strategy lacks standardized in vitro dissolution methods due to the difficulties in recreating implant formation in vitro that is biomimicry and with reproducible and controllable shape and dimensions. In the present study, an innovative, adapter-based in vitro release testing method was developed to solve this problem. Two distinctively different in situ forming implants (a risperidone formulation (suspension) consisting of PLGA dissolved in N-methyl pyrrolidone (NMP), where risperidone powder was suspended to form a drug suspension, and a naproxen formulation (solution) consisting of PLGA dissolved in NMP, where naproxen was completely dissolved to form a solution), were used as model in situ-forming implants. The results revealed that the implants formed in the custom-designed adapter with a water-dissolvable polyvinyl alcohol (PVA) film were bio-mimicking and reproducible in both shape and burst release of drug according to rabbit data. For both the suspension and solution formulations, this adapter-based in vitro release testing method resulted in consistent release data. Compared with a direct injection in vitro release testing method, the release profiles generated using the adapter-based method were capable of distinguishing the different release phases (initial release within 24 h, diffusion-facilitated release, and degradation-controlled release). In addition, the adapter-based method could discriminate formulation and dissolution apparatus changes and could be utilized to develop accelerated release testing methods. This adapter-based method has the promise of wide use in release testing of in situ forming implant formulations and has the potential to be used in the development of in vivo-predictive in vitro release methods.
KW - Dissolution adapter
KW - In situ forming implants
KW - In vitro release testing
KW - Naproxen
KW - Polyvinyl alcohol film
KW - Risperidone
UR - http://www.scopus.com/inward/record.url?scp=85129333030&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2022.121777
DO - 10.1016/j.ijpharm.2022.121777
M3 - Article
C2 - 35489601
AN - SCOPUS:85129333030
SN - 0378-5173
VL - 621
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 121777
ER -