On the mechanisms of formation of spherical agglomerates

Thati, Jyothi; Rasmuson, Åke C.

doi:10.1016/j.ejps.2011.01.001

Cited by 57 publications

(60 citation statements)

References 17 publications

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“…However, the agglomeration process may be complex in the former way since some bridging liquid may act as emulsifier. The droplets of drug solution added into the poor solvent may have a certain life time as reported by Thati and Rasmuson 6.…”

Section: Introductionmentioning

confidence: 79%

Size Control of Atorvastatin Calcium Particles Based on Spherical Agglomeration

Zhang

et al. 2015

Chem Eng & Technol

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Atorvastatin calcium (AC) spherical crystals were prepared by spherical agglomeration. CH 2 Cl 2 acting as bridging liquid was added together with the drug solution or after the antisolvent precipitation process. Polymorph transformation in antisolvent crystallization and agglomeration processes was observed by focusedbeam reflectance measurement (FBRM). The results suggested the occurrence of an immediate agglomeration when CH 2 Cl 2 was added together with the drug solution. Size-controllable AC spherical crystals with improved flowability and compressibility can be obtained by adjusting the amount of CH 2 Cl 2 and the stirring speed. The improved compaction behavior of the AC particles can be applied for direct tableting. A higher stirring speed can reduce the amount of bridging liquid which is required for effective agglomeration. It was a prerequisite for fine particles to be wetted by the bridging liquid in the spherical agglomeration process.

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Section: Introductionmentioning

confidence: 79%

Size Control of Atorvastatin Calcium Particles Based on Spherical Agglomeration

Zhang

et al. 2015

Chem Eng & Technol

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“…Katta and coworkers (30) noticed no change in the particle size of agglomerated benzoic acid with an increased volume of bridging liquid. However, it can be concluded from other studies that if the quantity of bridging liquid is too small, there is no significant agglomeration and when too much bridging liquid is used, the agglomerates become soft and pasty (18,28,31). Some authors emphasize the importance of the choice of bridging liquid and suggest how to determine the optimal one for spherical agglomeration.…”

Section: Spherical Agglomerationmentioning

confidence: 99%

“…Some researchers report on the enlargement of agglomerates with increasing amounts of bridging liquid (19,28), whereas in another study of the spherical agglomeration process the addition of a smaller amount of bridging liquid produced larger particles of acebutolol (up to 1,000 mm) and vice versa a larger amount of bridging liquid produced smaller particles (around 600 mm) (29). Katta and coworkers (30) noticed no change in the particle size of agglomerated benzoic acid with an increased volume of bridging liquid.…”

Section: Spherical Agglomerationmentioning

confidence: 99%

Spherical crystallization of drugs

Kovačič¹,

Vrečer²,

Planinšek³

2012

Acta Pharmaceutica

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The solid state properties of pharmaceutical compounds have a decisive impact on dosage form development, stability, and in vivo performance of the drug. Many pharmaceutical drugs are problematic per se due to their inappropriate physical and mechanical properties and poor aqueous solubility. The micromeritic properties of drug particles, such as shape and size, are of essential importance for the formulation of solid high--dose units (1). The particle size of poorly soluble drugs is always an issue due to its impact on dissolution properties. Micronized drug particles (smaller than 10 mm) have a large specific area and provide a way to improve the dissolution rate (2), but high energy input during the micronization process gives rise to increased free surface energy, electrostatic tendencies, and thus poor flowability and/or compressibility of powders and low bulk density (3), which makes them difficult to use in downstream processing in the pharmaceutical industry such as direct tablet-making or capsule-filling processes. In addition, micronized drug substances tend to agglomerate and the increase in surface area is not always reflected in improved dissolution (4). Spherical crystallization of drugs is the process of obtaining larger particles by agglomeration during crystallization. The most common techniques used to obtain such particles are spherical agglomeration and quasi-emulsion solvent diffusion. Ammonia diffusion systems and crystallo-co-agglomeration are extensions of these techniques. By controlling process parameters during crystallization, such as temperature, stirring rate, type and amount of solvents, or excipient selection, it is possible to control the formation of agglomerates and obtain spherical particles of the desired size, porosity, or hardness. Researchers have reported that the particles produced have improved micromeritic, physical, and mechanical properties, which make them suitable for direct compression. In some cases, when additional excipients are incorporated during spherical crystallization, biopharmaceutical parameters including the bioavailability of drugs can also be tailored.

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“…The dissolution medium used was 900 mL of gastric simulating fluid without enzymes (pH 1.2). Five milliliters of sample solution were withdrawn at predetermined time intervals (10,20,30,40,50, and 60 min) and then filtered through Whatman filter paper No: 40 and the same amount was replaced in the dissolution flask to maintain sink conditions. The amount of dissolved ibuprofen was analyzed spectrophotometrically at 221 nm.…”

Section: In Vitro Dissolution Studiesmentioning

confidence: 99%

“…The bridging liquid should be immiscible in the suspending medium, but capable of cementing the particles to be agglomerated. 10 This technique can also be exploited to increase solubility, dissolution, and hence bioavailability of poorly soluble drugs. 11 These modifications allow for the practice of more efficient manufacturing methods that could save time and reduce economic risk.…”

Section: Introductionmentioning

confidence: 99%

Preparation and in vitro evaluation of ibuprofen spherical agglomerates

Nagaraju

Penjuri

Saritha³

et al. 2018

tjps

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Bir anti-inflamatuvar ilaç olan ibuprofen, zayıf suda çözünürlüğü ile karakterize olup, farmakolojik etkileri sınırlar. Bu çalışmada aglomerasyonun mikromeritik özellikler ve çözünme üzerindeki etkilerinin incelenmesi amaçlanmıştır. Gereç ve Yöntemler: İbuprofen aglomeraları, su, diklorometan ve zayıf solvent olarak sırasıyla 57.5:12.5:30 oranında sıvı ve iyi çözücü köprü halindeki dimetil sülfoksit kullanılarak çözücü değiştirme yöntemi ile hazırlandı. Köprü sıvısı miktarı, ilave modu, sıcaklık ve karıştırma oranı gibi proses değişkenleri optimize edildi. Bulgular: Taramalı elektron mikroskobu çalışmaları, üretilen aglomeraların küresel olduğunu ve düzensiz şekli olduğunu göstermektedir. X-Işın Pudrası Difraksiyon spektrumu polimorfizm yokluğunu ortaya koydu. Diferansiyel tarama kalorimetrisi spektrumu, erime noktasında kristal modifikasyonun yokluğunu gösteren herhangi bir değişiklik göstermedi. Aglomeralar, saf ilaca kıyasla gelişmiş çözünürlük, çözünme hızı ve mikromeritik özellikler sergiledi. Sonuç: Anti-inflamatuvar çalışmalar Wistar suşu erkek albino sıçanlarında yürütülmüş ve ibuprofen aglomeraları saf ilaca göre daha iyi bir absorpsiyona bağlı olarak daha belirgin bir aktivite gösterdi. Saf ibuprofen ve aglomera için ülserojenik potansiyel çalışması gerçekleştirildi. İbuprofen aglomeraları ile tedavi edilen sıçanlarda daha iyi ülserojenik potansiyel gözlenmiştir. Anahtar kelimeler: İbuprofen, küresel toplanma, anti-inflamatuvar aktivite, ülserojenik potansiyel Objectives: Ibuprofen, an anti-inflammatory drug, is characterized by poor water solubility, which limits its pharmacologic effects. The present work aimed to the study the effect of agglomeration on the micromeritic properties and dissolution of ibuprofen. Materials and Methods: Ibuprofen agglomerates were prepared by solvent change method using water, dichloromethane and DMSO as poor solvent, bridging liquid and good solvent respectively in the ratio of 57.5:12.5:30. Process variables such as amount of bridging liquid, mode of addition, temperature and stirring rate were optimized. Results: SEM studies indicate that agglomerates produced were spherical and exhibit irregular shape. X-Ray Powder Diffraction spectra revealed the absence of polymorphism. DSC spectra showed no change in melting point indicating absence of crystal modification. The agglomerates exhibited improved solubility, dissolution rate and micromeritic properties compared to pure drug. Conclusion: Anti-inflammatory studies were conducted in Wistar strain male albino rats and ibuprofen agglomerates showed more significant activity than the pure drug which may be due to better absorption. Ulcerogenic potential study was carried out for pure ibuprofen and agglomerates. Better ulcerogenic potential was observed in ibuprofen agglomerates treated rats.

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On the mechanisms of formation of spherical agglomerates

Cited by 57 publications

References 17 publications

Size Control of Atorvastatin Calcium Particles Based on Spherical Agglomeration

Size Control of Atorvastatin Calcium Particles Based on Spherical Agglomeration

Spherical crystallization of drugs

Preparation and in vitro evaluation of ibuprofen spherical agglomerates

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