A proof-of-concept study of coupled supercritical CO2-assisted processes to produce solid self-assembled drug delivery systems (S-SADDS)

• Published in: Journal of crystal growth Vol. 616; p. 127245
• Main Authors: Massias, Thibault, de Paiva Lacerda, Suênia, Resende de Azevedo, Jacqueline, Letourneau, Jean-Jacques, Dos Santos, Philomène, Bolzinger, Marie-Alexandrine, Espitalier, Fabienne
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.08.2023; Elsevier
• Subjects: A1. Crystal morphology; A1. Recrystallization; B1. Nanomaterials; B1. Solid self-assembled drug delivery system; B3. RESS/SAS process; B3. Supercritical carbon dioxide process; Engineering Sciences; SAS; CO2; XRPD; EtOH; PVP; A1. Recrystallization; SD; B3. RESS/SAS process; PDI; SLN; S-SADDS; DSC; FTIR; B1. Nanomaterials; DSL; B3. Supercritical carbon dioxide process; NIF; VA; RESS/SAS; PC; scCO2; B1. Solid self-assembled drug delivery system; RESS; SADDS; SEM; A1. Crystal morphology; Nanomaterials; Solid self-assembled drug delivery system; RESS/SAS process; Crystal morphology; Supercritical carbon dioxide process; Recrystallization
• ISSN: 0022-0248; 1873-5002
• DOI: 10.1016/j.jcrysgro.2023.127245

•Optimization of solvent injection process to produce Solid Lipid Nanoparticles (SLN)•SLN were transposed to solid self-assembled drug delivery systems (S-SADDS)•Proof of concept of designing a coupled RESS/SAS supercritical CO2 process.•Simultaneous crystallization by innovative RESS/SAS successfully produced S-SADDS.•Controlled operating process conditions for complex solid production. The development of innovative drug delivery systems is currently under intense consideration to overcome bioavailability issues of poorly water-soluble drugs. Among the many existing delivery systems, self-assembled drug delivery systems (SADDS) are of great interest. Solid Lipid Nanoparticles (SLN), which are part of SADDS, have been widely studied in the pharmaceutical field since they are biodegradables and biocompatibles. However, stability of SLN suspension over time is limited and quick drug released were frequently observed. The development of solid SADDS (S- SADDS), to produce an on-demand delivery system, through a one-step production process has been designed to overcome these issues. The coupling of both Supercritical Carbon Dioxide (scCO2) assisted RESS and SAS processes (RESS/SAS) have been proposed as a proof-of-concept. This study was carried out in three steps: (i) the development and adjustment of operating conditions to produce SLN suspension using solvent injection process, (ii) the optimization of the formulation to produce SLN with a mean particle size diameter close to 100 nm and stable at least 24 h, (iii) the transposition of the SLN formulation composition into the RESS/SAS coupled process for the production of S-SADDS. SLN composed of stearic acid, PVP K30, phosphatidylcholine and nifedipine, with an average size under 100 nm and a zeta potential about −35 mV were obtained from the preliminary study. These results allowed the transposition of the optimal formulation into RESS/SAS crystallization process. The developed RESS/SAS scCO2-assisted processes demonstrate the simultaneous crystallization of a self-assembled formulation in a one step process. A control of operating conditions was also demonstrated through the generation of S- SADDS containing desired amount of nifedipine. The proof-of-concept process studied, seems to be very promising tool for the generation of complex solids, intermediate products or for the development of innovative drug delivery systems.