Solution Cocrystallization: A Scalable Approach for Cocrystal Production

Pawar, Nitin; Saha, Anindita; Nandan, Neelesh; Parambil, Jose V.

doi:10.3390/cryst11030303

Cited by 47 publications

(54 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As was shown with concentration courses at position m = M in diagrams (d) of Figures 3-7, desupersaturation measurements at a single point are performable in reasonable time-scales even for diffusion limited growth processes, which represent the fastest possible growth process. Hence, it is possible to retrieve the two unknown variables k g,i and g in mass transfer kinetic equations , e.g., Equation (22), from desupersaturation measurements.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Multi-Component Diffusion in the Vicinity of a Growing Crystal

Helfenritter

Kind

2022

Crystals

View full text Add to dashboard Cite

Co-crystallization from multi-component solutions occurs in many solids formation processes. The measurement or simulative description of concentration courses in the fluid vicinity of a growing crystalline substrate is difficult for such systems. These are relevant with respect to developing concentrations of crystallizing components at the solid-liquid interface due to diffusion fluxes in the solution. Concentrations may change such that unintended crystalline states can develop. With Fickian multi-component diffusion modeling we are able to simulate the timely evolution of the concentrations in the diffusion boundary layer during crystallization of various solid entities. Not only single solvate crystallization is modeled but also co-crystallization from multi-component solutions with different solvate states. The simulations are run with the assumption that diffusion limitation dominates. However, the model can be easily adapted to integration limitation. The interdependence of two diffusing components is taken into account in Fick’s multicomponent diffusion with a diffusion coefficient between these two components. We show that the consideration of so called cross-diffusion effects between dissolved materials can be neglected during crystallization of single decahydrates and during co-crystallization of anhydrous electrolytes. The presented model is also capable of fitting crystal growth kinetics with single point desupersaturation measurements in a thin film. In addition to the study of the kinetic parameters, the simulation allows the determination of the spatial concentration evolution from the single point concentration measurements.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Since crystal growth processes always involve diffusion steps, concentration profiles in the vicinity of growing crystals are transient [20]. Hence, the kinetics of co-crystal growth are of interest, respectively [21,22]. Of particular interest are the prevailing concentrations at the solid-liquid interface in the liquid phase.…”

Section: Introductionmentioning

confidence: 99%

Multi-Component Diffusion in the Vicinity of a Growing Crystal

Helfenritter

Kind

2022

Crystals

View full text Add to dashboard Cite

show abstract

“…Like other solution-based methods, the RCM has the disadvantage of needing to separate the formed cocrystals from the solvent [ 49 ]. It can also generate undesirable solvated or hydrated cocrystals, in addition to generating waste if non-environmentally friendly solvents are used.…”

Section: Techniques For Obtaining Cocrystalsmentioning

confidence: 99%

Obtaining Cocrystals by Reaction Crystallization Method: Pharmaceutical Applications

et al. 2021

View full text Add to dashboard Cite

Cocrystals have gained attention in the pharmaceutical industry due to their ability to improve solubility, stability, in vitro dissolution rate, and bioavailability of poorly soluble drugs. Conceptually, cocrystals are multicomponent solids that contain two or more neutral molecules in stoichiometric amounts within the same crystal lattice. There are several techniques for obtaining cocrystals described in the literature; however, the focus of this article is the Reaction Crystallization Method (RCM). This method is based on the generation of a supersaturated solution with respect to the cocrystal, while this same solution is saturated or unsaturated with respect to the components of the cocrystal individually. The advantages of the RCM compared with other cocrystallization techniques include the ability to form cocrystals without crystallization of individual components, applicability to the development of in situ techniques for the screening of high quality cocrystals, possibility of large-scale production, and lower cost in both time and materials. An increasing number of scientific studies have demonstrated the use of RCM to synthesize cocrystals, mainly for drugs belonging to class II of the Biopharmaceutics Classification System. The promising results obtained by RCM have demonstrated the applicability of the method for obtaining pharmaceutical cocrystals that improve the biopharmaceutical characteristics of drugs.

show abstract

“…[11][12][13] Moreover, each method has its own limitations. 14 Mechanochemical methods can lead to an undesirable transition of a mixture to an amorphous state. 15 The nature of the solvent used determines (among other equally important factors) the final product formed and affects the results of screening by slow crystallization or LAG methods.…”

Section: Introductionmentioning

confidence: 99%