Continuous manufacturing of co-crystals: challenges and prospects

The last decade has witnessed extensive growth in the field of co-crystallization for mitigating the solubility and dissolution-related issues of poorly soluble drugs. This is largely because co-crystals can modify the physicochemical properties of drugs without any covalent modification in the drug...

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Published inDrug delivery and translational research Vol. 8; no. 6; pp. 1726 - 1739
Main Authors Chavan, Rahul B., Thipparaboina, Rajesh, Yadav, Balvant, Shastri, Nalini R.
Format Journal Article
LanguageEnglish
Published New York Springer US 01.12.2018
Subjects
Aminobutyrates - chemistry
Biomedical and Life Sciences
Biomedicine
Crystallization
Drug Combinations
Pharmaceutical Preparations - chemistry
Pharmaceutical Sciences/Technology
Review Article
Solubility
Tetrazoles - chemistry
United States
United States Food and Drug Administration
Valsartan - chemistry
United States
Hot melt extrusion
Marketed co-crystals
PAT
Quality by design
RAM
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Summary:The last decade has witnessed extensive growth in the field of co-crystallization for mitigating the solubility and dissolution-related issues of poorly soluble drugs. This is largely because co-crystals can modify the physicochemical properties of drugs without any covalent modification in the drug molecules. The US Food and Drug Administration (FDA) now considers drug products that are designed to contain a new co-crystal, analogous to new polymorph of the active pharmaceutical ingredient (API). This positive change in regulatory perspective coupled with successful commercialization of valsartan-sacubitril co-crystal (Entresto, Novartis) has now brought co-crystals into focus, in both industries as well as academia. Co-crystal prediction, screening, and synthesis have been reported in literature; however, co-crystal production at a larger scale needs further investigations. With this aim, the article describes various continuous methods for co-crystal production, along with in-line monitoring during co-crystal production, emphasizing on process analytical technology (PAT). In addition, the scale-up issues of continuous and batch co-crystallization and other suitable techniques for pharmaceutical scale up are detailed. Quality control aspects and regulatory viewpoint crucial for commercial success are elaborated in the future perspective.
ISSN:2190-393X
2190-3948
DOI:10.1007/s13346-018-0479-7