Improvement of drug processability in a connected continuous crystallizer system using formulation additive

[Display omitted] Continuous crystallization in the presence of polymer additives is a promising method to omit some drug formulation steps by improving the technological and also pharmacological properties of crystalline active ingredients. Accordingly, this study focuses on developing an additive-...

Full description

Saved in:
Bibliographic Details
Published in:International journal of pharmaceutics 2023-03, Vol.635, p.122725-122725, Article 122725
Main Authors: Tacsi, Kornélia, Stoffán, György, Galata, Dorián László, Pusztai, Éva, Gyürkés, Martin, Nagy, Brigitta, Szilágyi, Botond, Nagy, Zsombor Kristóf, Marosi, György, Pataki, Hajnalka
Format: Article
Language:English
Subjects:
Acetylsalicylic acid reaction mixture
Aspirin
Continuous crystallization
Crystallization - methods
Crystallization additives
Design of experiments
Drug flowability improvement
Mixed suspension mixed product removal
Phase Transition
Plug flow crystallizer
Polymers
Povidone
Solubility
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:[Display omitted] Continuous crystallization in the presence of polymer additives is a promising method to omit some drug formulation steps by improving the technological and also pharmacological properties of crystalline active ingredients. Accordingly, this study focuses on developing an additive-assisted continuous crystallization process using polyvinylpyrrolidone in a connected ultrasonicated plug flow crystallizer and an overflow mixed suspension mixed product removal (MSMPR) crystallizer system. We aimed to improve the flowability characteristics of small, columnar primary plug flow crystallizer-produced acetylsalicylic acid crystals as a model drug by promoting their agglomeration in MSMPR crystallizer with polyvinylpyrrolidone. The impact of the cooling antisolvent crystallization process parameters (temperature, polymer amount, total flow rate) on product quality and quantity was investigated. Finally, a spatially segmented antisolvent dosing method was also evaluated. The developed technology enabled the manufacture of purified, constant quality products in a short startup period, even with an 85% yield. We found that a higher polymer amount (7.5–14%) could facilitate agglomeration resulting in “good” flowability without altering the favorable dissolution characteristics of the primary particles.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2023.122725