Experimental design approach for development of cocrystals and immediate release cocrystal tablet of atorvastatin calcium for enhancement of solubility and dissolution

Trivedi, Hemangi R.; Borkar, Dhananajay S.; Puranik, P. K.

doi:10.35333/jrp.2020.226

Cited by 3 publications

(2 citation statements)

References 23 publications

(36 reference statements)

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“…Additionally, these agglomerate particles still existed after 10 h, and it can be inferred that this part of ATC will not be absorbed by the body, thus causing the loss of the API. Surprisingly, this dissolution rate of the ATC crystals of the most uniform form I was also the fastest rate among the rates in the present literature, which included ATC powders made by milling, , spray-drying, , cocrystallizing, , intensifying, coagglomerating, and so on. This result indicated that the crystal products prepared by bistream AC had the potential to produce the best medicines of ATC.…”

Section: Resultsmentioning

confidence: 55%

Crystal Agglomeration and Microscopic Molecular Exchange Mechanism in Antisolvent Crystallization

Qin,

Yang

2024

Crystal Growth & Design

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Agglomeration is a significant challenge in antisolvent crystallization, especially when it comes to crystallizing insoluble drugs. This study aimed to address this issue by taking a unique, dynamic molecular perspective and proposing a solution based on microscopic molecular exchange. Atorvastatin calcium, a widely prescribed medication for lowering blood lipids, was used as a case for antisolvent crystallization, which is also prone to agglomeration. Kinetic experiments revealed the rapid exchange between solvent and antisolvent, leading to precipitation occurring within a mere 0.0333 s. Thermodynamic investigations further showed that each droplet had the potential to generate an astonishing equivalent nucleation rate of up to 5 billion nuclei per second. The rapid precipitation and small nucleation region, coupled with a large number of nuclei, worsened the crystal agglomeration problem. However, it was found that this molecular exchange process can be slowed by the solvent composition. Specifically, when the methanol mole fraction in the crystallization system reached approximately 50%, the equivalent nucleation rate decreased significantly to about 100 million per second. Armed with this crucial finding, a strategy was devised to overcome agglomeration by simultaneously adding the solution and antisolvent to maintain a lower exchange rate, which effectively avoided agglomeration and promoted the purification of atorvastatin calcium.

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Section: Resultsmentioning

confidence: 55%

Crystal Agglomeration and Microscopic Molecular Exchange Mechanism in Antisolvent Crystallization

Qin,

Yang

2024

Crystal Growth & Design

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“…HSP is used as an indicator of the miscibility between the component molecules to predict the likelihood of cocrystal formation. ,, In this model, the total force of various interactions can be divided into several partial solubility parameters, namely, dispersion (δ d ), polarity (δ p ), and hydrogen bonding (δ h ). , Each partial solubility parameter corresponds to the possibility of intermolecular interactions between molecules. Total solubility parameter (δ t ) is defined as The miscibility of compound molecules is estimated by various criterions, and all of them are based on the principle of “like dissolves like”.…”

Section: Methodsmentioning

confidence: 99%

Evaluation on Cocrystal Screening Methods and Synthesis of Multicomponent Crystals: A Case Study

Zhang

Yao

et al. 2021

Crystal Growth & Design

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Screening of suitable coformers is a major challenge during the development of cocrystals. To guide and simplify the cocrystal synthesis process, we evaluated three different predictive methods as well as their combinations during the cocrystallization of 2-amino-4,6-dimethoxypyrimidine (MOP) with 63 components. The conductor-like screening model for the real solvents (COSMO-RS) approach offered the best predictive results among three methods with an overall success rate of 84.1%. When combined with molecular complementarity (MC) analysis, the success rate was up to 85.7%. The Hansen solubility parameters (HSP) method did not deliver a satisfying outcome no matter if used individually or in combination for the MOP system. In addition, based on the screened results, 21 new solid phases of MOP were experimentally observed. Among them, the crystal structures of 10 multicomponent crystals (cocrystals and salts) were revealed by single crystal X-ray diffraction analysis (SCXRD), and their thermodynamic and spectroscopy properties were also characterized. The Hirshfeld surface analysis and the molecular electrostatic potential (MEP) surface analysis were conducted to explore the interactions in multicomponent crystals and the origin for salts and cocrystals. The cases in this study not only enriched the solid forms of MOP, evidenced the feasibility of the combined screening method, but also set an effective example for choosing potential coformers to prepare multicomponent crystals.

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Cocrystals and Drug–Drug Cocrystals of Anticancer Drugs: A Perception towards Screening Techniques, Preparation, and Enhancement of Drug Properties

Kara

Rathnanand

2022

Crystals

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The most favored approach for drug administration is the oral route. Several anticancer drugs come under this category and mostly lack solubility and oral bioavailability, which are the most common causes of inadequate clinical efficiency. Enhancing oral absorption of anticancer drugs with low aqueous solubility and drug impermeability is currently an effective area of research. Many scientists have looked into pharmaceutical cocrystals as a way to improve the physicochemical properties of several anticancer drugs. Benefits of pharmaceutical cocrystals over other solid forms may include improved solubility, bioavailability, and a reduced susceptibility for phase transition. Cocrystal strategy also stands as a green synthesis tool by using very limited organic solvents during its formulation. Having so many advantages, to date, the reported cocrystals and drug–drug cocrystals of anticancer drugs are limited. Here we review the pharmaceutical cocrystals and drug–drug cocrystals of the anticancer drugs reported in the last decade and their future in imaging, and also shed light on the opportunities and challenges for the development of anticancer drug cocrystals.

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Experimental design approach for development of cocrystals and immediate release cocrystal tablet of atorvastatin calcium for enhancement of solubility and dissolution

Cited by 3 publications

References 23 publications

Crystal Agglomeration and Microscopic Molecular Exchange Mechanism in Antisolvent Crystallization

Crystal Agglomeration and Microscopic Molecular Exchange Mechanism in Antisolvent Crystallization

Evaluation on Cocrystal Screening Methods and Synthesis of Multicomponent Crystals: A Case Study

Cocrystals and Drug–Drug Cocrystals of Anticancer Drugs: A Perception towards Screening Techniques, Preparation, and Enhancement of Drug Properties

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