Development of long-acting injectable suspensions by continuous antisolvent crystallization: An integrated bottom-up process

Nandi, Snehashis; Padrela, Luis; Tajber, Lidia; Collas, Alain

doi:10.1016/j.ijpharm.2023.123550

Cited by 4 publications

(11 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MCR-CLASC setup described in this study, as well as the operating parameters used to generate a stable ITZ suspension using a Y mixer in a microchannel reactor-based CLASC process, were optimized previously by our group [ 54 ]. Therefore, 100 mg/g ITZ in NMP and 0.5% w / w Vit E TPGS 1000 aqueous solution were used as the S:AS combination; the experiments were performed at 25 °C and kept at the same temperature during storage.…”

Section: Resultsmentioning

confidence: 99%

“…An optimized MCR-CLASC setup was assembled to generate ITZ suspensions in continuous mode, as explained in detail in the earlier work published by our group [ 54 ]. Two sets of high-precision Teledyne ISCO pumps were connected through a PEEK microchannel reactor (using a Y mixer as a fluidic mixing device) with an internal diameter of 0.5 mm via PFA tubing with a diameter of 0.33 mm and a residence volume of 1.7 µL.…”

Section: Methodsmentioning

confidence: 99%

“…The impact of the five most promising parenterally approved excipients for the stabilization of ITZ suspensions based on an earlier optimization study conducted on the MCR-CLASC process [ 54 ] was investigated in the SCT-CLASC process and compared against pure water without any stabilizer as a reference. A quantity of 1 g of surfactant, Vit E TPGS 1000, POL 188, POL 338, or POL 407 was dissolved in 199 g of Millipore water at 25 °C to create 0.5% w / w aqueous solutions.…”

Section: Methodsmentioning

confidence: 99%

“…The dissolution profiles were studied in 500 mL of 1% w / v Tween 20 + 0.1N HCl (pH 1.2) release medium at 37 ± 0.5 °C in a temperature-controlled water bath with submerged stirring at 300 rpm, as described in the earlier work published by our group [ 54 ]. This medium was selected as the discriminatory medium for testing differences in the properties of the ITZ LAI suspensions, considering the impact of particle size and ensuring complete release.…”

Section: Methodsmentioning

confidence: 99%

“…In the present work, a continuous microfluidic liquid antisolvent crystallization (SCT-CLASC) process was developed using itraconazole (ITZ)–water–NMP as a model system and a Secoya SCT-LAB microfluidic device. The methodology was utilized to produce stable LAI suspensions [ 19 ] with PSDs between 1 and 10 µm, with higher API loading and/or lower excipient use compared to the pre-optimized continuous microchannel reactor-based LASC process (MCR-CLASC) described in an earlier paper [ 54 ]. This work investigates the impact of the solvent-to-antisolvent ratio, the solvent-to-antisolvent stream flow rate, the type of static mixing device, and the effect of the stabilizer type and concentration on the post-precipitation feed suspension using a one-factor-at-a-time (OFAT) approach.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Continuous Microfluidic Antisolvent Crystallization as a Bottom-Up Solution for the Development of Long-Acting Injectable Formulations

Nandi,

Verstrepen,

Hugo Silva

et al. 2024

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

A bottom-up approach was investigated to produce long-acting injectable (LAI) suspension-based formulations to overcome specific limitations of top-down manufacturing methods by tailoring drug characteristics while making the methods more sustainable and cost-efficient. A Secoya microfluidic crystallization technology-based continuous liquid antisolvent crystallization (SCT-CLASC) process was optimized and afterward compared to an earlier developed microchannel reactor-based continuous liquid antisolvent crystallization (MCR-CLASC) setup, using itraconazole (ITZ) as the model drug. After operating parameter optimization and downstream processing (i.e., concentrating the suspensions), stable microsuspensions were generated with a final solid loading of 300 mg ITZ/g suspension. The optimized post-precipitation feed suspension consisted of 40 mg ITZ/g suspension with a drug-to-excipient ratio of 53:1. Compared to the MCR-CLASC setup, where the post-precipitation feed suspensions contained 10 mg ITZ/g suspension and had a drug-to-excipient ratio of 2:1, a higher drug concentration and lower excipient use were successfully achieved to produce LAI microsuspensions using the SCT-CLASC setup. To ensure stability during drug crystallization and storage, the suspensions’ quality was monitored for particle size distribution (PSD), solid-state form, and particle morphology. The PSD of the ITZ crystals in suspension was maintained within the target range of 1–10 µm, while the crystals displayed an elongated plate-shaped morphology and the solid state was confirmed to be form I, which is the most thermodynamically stable form of ITZ. In conclusion, this work lays the foundation for the SCT-CLASC process as an energy-efficient, robust, and reproducible bottom-up approach for the manufacture of LAI microsuspensions using ITZ at an industrial scale.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations