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

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(3), P. 376 - 376

Published: March 8, 2024

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

Language: Английский

---

Particle size matters: The impact of particle size on properties and performance of long-acting injectable crystalline aqueous suspensions

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113793 - 113793

Published: April 1, 2025

Language: Английский

---

Suspension-Based Long-Acting Injectables

Published: Jan. 1, 2025

Language: Английский

---

Tailoring the use of excipients in bottom-up production of naproxen crystal suspensions via membrane technology

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 652, P. 123846 - 123846

Published: Jan. 23, 2024

Long-acting crystal suspensions of active pharmaceutical ingredients (API) mostly comprised an API, a suspension media (water) and excipients provide sustained API release over time. Excipients are crucial for controlling particle size to achieve the stability crystals in suspension. A bottom-up process was designed produce long-acting whilst investigating excipient requirements during production subsequent storage. PVP K30 emerged as most effective generating stable naproxen with desired 1 15 μm, using ethanol solvent water anti-solvent. Calculations, performed based on properties assuming complete adsorption surface, revealed lower storage compared initial generation. Consequently, membrane-based diafiltration used determine fine-tune concentration post-crystallization. seven-stage removed 98 % present thereby reducing PVP-to-naproxen ratio from 1:2 1:39 without impacting This work provides insights into at various stages introduce precise control after crystallization.

Language: Английский

---

Optimizing extrusion processes and understanding conformational changes in itraconazole amorphous solid dispersions using in-line UV–Vis spectroscopy and QbD principles

International Journal of Pharmaceutics X, Journal Year: 2024, Volume and Issue: 8, P. 100308 - 100308

Published: Nov. 26, 2024

Language: Английский

---