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关于共晶,你想知道的

日期: 2020-01-08
浏览次数: 21

Co-crystals are drawing much attention nowadays as they may exhibit better performances, concerning stability, solubility and processability, compared to single-component polymorphs. As a definition, co-crystals are crystalline materials composed of two or more different molecules, typically active pharmaceutical ingredient (API) and co-crystal formers (‘coformers’), in the same crystal lattice.

 

A diagram of classification of solid forms are shown in Figure 1. Co-crystals are different from salts in that molecules are combined with supramolecular interactions, instead of ionic interactions. From a physical chemistry and regulatory perspective, co-crystals can be viewed as a special case of solvates and hydrates, wherein the second component, the coformer, is not a solvent (including water), and is typically nonvolatile.

 

关于共晶,你想知道的

Figure 1. Classification of solid forms

 

According to FDA guidance, for NDAs and ANDAs containing or claiming to contain a co-crystal form, applicants should submit appropriate data that support the following:

Ø Provide evidence to demonstrate that both the API and coformers are present in the unit cell.

Ø If both API and coformer have ionizable functional groups, a conclusion that the component API and coformer co-exist in the co-crystal which interact nonionically.

Ø Assurance that substantial dissociation of the API from its co-crystal form occurs before reaching the site of pharmacological activity. Given that the interaction of the API with its coformer is of similar magnitude to the interaction of the API with solvents in solvates, an in vitro evaluation based on dissolution and/or solubility is generally considered sufficient to demonstrate that the API dissociates from its coformer before reaching the site of pharmacological activity.

 

A co-crystal with a pharmaceutically acceptable coformer that meets the above conditions can be considered to be a pharmaceutical co-crystal and has a regulatory classification similar to that of a polymorph of the API. Specifically, it is not regarded as a new API. From a regulatory perspective, drug products that are designed to contain a new co-crystal are considered analogous to a new polymorph of the API. A co-crystal that is composed of two or more APIs (with or without additional inactive coformers) will be treated as a fixed-dose combination product and not a new single API.

 

Apart from regulatory considerations, efficient preparations of co-crystals are essential for pharmaceutical companies. Methods are usually divided into solid-based and solution-based. And the choice of methods is based on properties of the molecules. Nycrist has been focusing on the preparation of co-crystals and therefore can assist you in the discovery of a more bio-available, stable and processable form in an efficient manner. For details, please contact us!

 


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