Spherical Crystallization of Drugs

Javadzadeh, Yousef; Vazifehasl, Zhila; Dizaj, Solmaz Maleki; Mokhtarpour, Masumeh

doi:10.5772/59627

Cited by 7 publications

(13 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Agglomerates formed were with optimal sphericity with AR of 0.86 and Q 15 of 68%. HPC improved dissolution despite the formation of thick plates owing to its deaggregation tendencies . Reduction in size of the agglomerates was seen when a lower amount of HPC was employed (0.1% of E3 and 0.05% of HPC).…”

Section: Resultsmentioning

confidence: 97%

“…In spherical agglomeration, the spherical morphology is obtained due to optimal mechanical force imparted for a specific period during stirring and is one of the main parameters influencing average diameter of the agglomerate crystals. Agitation speed mainly affects the crystallization tendency and the dispersion of the bridging liquid throughout the system . Higher speeds lead to production of fines while lower speeds lead to formation of the large and irregular agglomerates.…”

Section: Resultsmentioning

confidence: 99%

“…It provides a platform for the development of readily compressible materials with improved flow and dissolution aiding in development of blends for direct compression. − It produces spherical particles with improved micromeritics which consequently influence physical and mechanical properties, rendering the drugs suitable for direct tabletting . It is a simple technique which involves dissolution of the drug in good solvent (solvent in which drug has good solubility) followed by addition of poor solvent (solvent in which drug has low solubility) along with bridging liquids like chloroform, dichloromethane (DCM), hexane, and ethyl acetate under continuous stirring . Polymers are generally added to the aqueous phase.…”

Section: Introductionmentioning

confidence: 99%

“…Agglomeration of needles into spherical systems is well documented, ,,,,,− but to date no existing literature has discussed agglomeration of plates into spheroids. A systematic study was designed to overcome the problem of poor compressibility and flow properties of etodolac through spherical crystallization.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Spherical Agglomeration of Platy Crystals: Curious Case of Etodolac

Jitkar

Thipparaboina

Chavan

et al. 2016

Crystal Growth & Design

View full text Add to dashboard Cite

The present study reports an intriguing case study of agglomeration of platy crystals into spheroids. Etodolac a nonsteroidal anti-inflammatory drug is mainly used for rheumatoid arthritis, with emerging applications in management of prostate cancer and Alzheimer’s disease. It is a BCS class II drug with poor flow and compressibility issues. Recrystallization using various solvents resulted in platy crystals. Different polymers like hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and polyvinylpyrrolidone (PVP), and copolymers poly(ethylene glycol) (PEG 400), poly(vinyl alcohol) (PVA), and Poloxamer were explored at various concentrations and in different combinations to provide systematic inputs for the development of spherical agglomerates with optimal sphericity, dissolution, yield, and mechanical properties suitable for direct compression. Effects of different process parameters on agglomeration were studied. Agglomerates obtained were characterized using SEM, DSC, and P-XRD and were evaluated for enhancements in flow, compressibility, and dissolution. All the agglomerates have shown improved flow properties and compressibility. Unlike plain drug, all spherical agglomerates have shown acceptable plastic behavior during compression studies resulting in tablets at low pressures. Agglomerates developed using a unique combination of HPMC, HPC, and PEG has shown 94% drug release in 15 min. The recrystallized spherical agglomerates can be used as readily compressible material for continuous manufacturing.

show abstract

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Spherical Agglomeration of Platy Crystals: Curious Case of Etodolac

Jitkar

Thipparaboina

Chavan

et al. 2016

Crystal Growth & Design

View full text Add to dashboard Cite

show abstract

“…Simultaneously, the crystals are transformed into spherical aggregates. To date, these approaches have been widely used in the preparation of spherical organic drugs and have become an outstanding strategy for designing the desired products with improved physical and mechanical properties. − However, the formation mechanism of spherical crystals has not been fully understood, because the fast kinetics resulting from the antisolvent crystallization make the observation of the morphological evolution details difficult . Moreover, compared with organic drug molecules, only a few literature reports ,, have discussed the methods to prepare the spherical crystals of organic explosive molecules, especially for those molecules containing strong intra- and intermolecular hydrogen bonds, such as 2,4,6-trinitrobenzene-1,3,5-triamine (TATB), 3,5-dinitropyrazine-2,6-diamine-1-oxide (LLM-105), and 2,2-dinitroethylene-1,1-diamine (FOX-7).…”

Section: Introductionmentioning

confidence: 99%

A Novel Spherulitic Self-Assembly Strategy for Organic Explosives: Modifying the Hydrogen Bonds by Polymeric Additives in Emulsion Crystallization

Zhou

Zhang

et al. 2018

Crystal Growth & Design

View full text Add to dashboard Cite

A novel strategy to prepare spherical crystals of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) has been developed by introducing polymeric additives into the antisolvent emulsion crystallization. The spherical crystals are induced by modifying the intermolecular hydrogen bonds network of LLM-105. The results show that the concentration of polyvinylpyrrolidone (PVP), which acts as a polymeric additive, is a crucial factor to get quite different morphologies of LLM-105 crystal products. X-like shaped crystals have been produced in the absence of PVP. In contrast, spherical crystals have been obtained in the presence of PVP. Importantly, LLM-105 spherulites with a mean particle size of 78.0 μm can be obtained by adding a proper amount of PVP, which has a narrow size distribution (CV = 31.2). In addition, time-resolved morphological evolution processes of X-like shaped and spherical crystals have been performed. Meanwhile, 1H NMR experiments also have been conducted to understand the intermolecular hydrogen bonds between LLM-105 molecules and the polymer. Inspired by the result of the above experiments, an LLM-105 spherulitic formation mechanism has been proposed. Furthermore, LLM-105 spherulites exhibit more excellent mechanical and safety properties. It is suggested that these spherulites have a great potentiality in the military application. Therefore, this polymer-induced spherical crystallization method is significantly important for the design and fabrication of organic small molecules with spherical shapes.

show abstract

References

2023

Crystallization of Organic Compounds

View full text Add to dashboard Cite

Spherical Crystallization of Drugs

Cited by 7 publications

References 53 publications

Spherical Agglomeration of Platy Crystals: Curious Case of Etodolac

Spherical Agglomeration of Platy Crystals: Curious Case of Etodolac

A Novel Spherulitic Self-Assembly Strategy for Organic Explosives: Modifying the Hydrogen Bonds by Polymeric Additives in Emulsion Crystallization

References

Contact Info

Product

Resources

About