The Effect of the Particle Size Reduction on the Biorelevant Solubility and Dissolution of Poorly Soluble Drugs with Different Acid-Base Character

Csicsák, Dóra; Szolláth, Rita; Kádár, Szabina; Ambrus, Rita; Bartos, Csilla; Balogh, Eszter; Antal, István; Köteles, István; Tőzsér, Petra; Bárdos, Vivien; Horváth, Péter; Borbás, Enikő; Takács‐Novák, Krisztina; Sinkó, Bálint; Völgyi, Gergely

doi:10.3390/pharmaceutics15010278

Cited by 10 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Wahyudiono et al reported that the injection of a greater concentration of phospholipids, comprising POPC, into a medium brings about an enhancement in liposome size and PDI [ 53 ]. Previous studies by Csicsák et al and Lee mentioned that the reduction in the size of drug particles can increase their surface area, resulting in an improvement in their dissolution and bioavailability, along with a narrow size distribution for drug particles [ 54 , 55 ]. In other words, decreasing the concentration of POPC utilized to produce liposomal CRE-SD may lead to reduced liposome size and PDI, as well as enhanced bioavailability.…”

Section: Discussionmentioning

confidence: 99%

Modified Curcuminoid-Rich Extract Liposomal CRE-SDInhibits Osteoclastogenesis via the Canonical NF-κB Signaling Pathway

Jantarawong,

Swangphon,

Lauterbach

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

Curcuminoids, namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are the major active compounds found in Curcuma longa L. (turmeric). Although their suppressive effects on bone resorption have been demonstrated, their pharmacokinetic disadvantages remain a concern. Herein, we utilized solid dispersion of a curcuminoid-rich extract (CRE), comprising such curcuminoids, to prepare CRE-SD; subsequently, we performed liposome encapsulation of the CRE-SD to yield liposomal CRE-SD. In vitro release assessment revealed that a lower cumulative mass percentage of CRE-SD was released from liposomal CRE-SD than from CRE-SD samples. After culture of murine RANKL-stimulated RAW 264.7 macrophages, our in vitro examinations confirmed that liposomal CRE-SD may impede osteoclastogenesis by suppressing p65 and IκBα phosphorylation, together with nuclear translocation and transcriptional activity of phosphorylated p65. Blind docking simulations showed the high binding affinity between curcuminoids and the IκBα/p50/p65 protein complex, along with many intermolecular interactions, which corroborated our in vitro findings. Therefore, liposomal CRE-SD can inhibit osteoclastogenesis via the canonical NF-κB signaling pathway, suggesting its pharmacological potential for treating bone diseases with excessive osteoclastogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Modified Curcuminoid-Rich Extract Liposomal CRE-SDInhibits Osteoclastogenesis via the Canonical NF-κB Signaling Pathway

Jantarawong,

Swangphon,

Lauterbach

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Существует несколько подходов, улучшающих абсорбцию вещества в ЖКТ за счет повышения растворимости и/или скорости растворения. Методы повышения растворимости делятся на химические (соли [1], сокристаллы [2] и пролекарства [3]) и физические (комплексообразование [4], создание самоэмульгирующихся композиций, липосомальные технологии [5], микронизация [6], преобразование в аморфную форму и создание твердых дисперсных систем (ТДС) на основе полимерных носителей [7]). Химические модификации имеют весьма ограниченное применение ввиду особенностей активной молекулы.…”

Section: фармацевтическая технологияunclassified

“…Уменьшение размера частиц -одна из самых распространенных технологий повышения растворимости лекарств, поскольку растворимость действующего вещества (ДВ) неразрывно связана с удельной поверхностью частиц. Данный метод широко используется в фармацевтической технологии для повышения биодоступности плохо растворимых активных фармацевтических субстанций (АФС) [6], что позволяет снизить терапевтическую дозу лекарственного вещества (ЛВ) и уменьшить количество побочных эффектов. Однако уменьшение размера частиц оказывает сравнительно небольшое влияние на растворимость ДВ, поскольку повышает не предельную растворимость АФС, а скорость его растворения за счет увеличения площади, доступной для сольватации.…”

Section: фармацевтическая технологияunclassified

Composition and Technology Development for Obtaining Amorphous Solid Dispersion of Ebastine by Hot Melt Extrusion to Increase Dissolution Rate

Gusev,

Aliev,

Generalova

et al. 2023

Razrabotka i registraciâ lekarstvennyh sredstv

View full text Add to dashboard Cite

Introduction. Ebastine is a second-generation antihistamine drug available in the form of orally disintegrating tablets and film-coated tablets. Ebastine substance exhibits high bioavailability, but low solubility in water and gastrointestinal tract media. The technology of solid dispersions based on polymer carriers by hot melt extrusion is proposed to solve the problem of ebastine low solubility.Aim. Composition development of extrudate and its production technology to create an amorphous solid dispersion of ebastine in oder to increase the recovery rate and bioavailability.Materials and methods. Ebastin micronized (JSC "Active Component", Russia); ebastin crystalline (Arevipharma GmbH, Germany); VIVAPHARM® PVP/VA 64 (JRS Pharma GMbH & Co. KG, Germany). Extrudates were obtained on a HAAKE™ miniCTW co-rotating twin-screw laboratory extruder (Thermo Fisher Scientific, Germany). Extrudates were studied by differential scanning calorimetry, synchronous thermal analysis, powder X-ray diffraction and FTIR-spectroscopy. The quantitative content of the active ingredient was determined by spectrophotometry. The content of related impurities in the amorphous solid dispersion of ebastine was determined by HPLC.Results and discussion. The technology of amorphous solid dispersion of ebastine by hot melt extrusion was developed. The pharmacokinetic properties of ebastine were significantly improved. The process of obtaining solid dispersion with 20 % of ebastine was optimized in order to reduce the content of impurities in the extrudate.Conclusion. The maximum concentration of ebastine for proper quality amorphous solid dispersion based on PVP/VA64 amounted to 20 %. Obtaining a solid dispersion by hot melt extrusion with ebastine content in PVP/VA64 higher than 30 % is impossible because the melt does not possess the glass transition property.

show abstract

“…Over 50 years ago, crystal engineering was applied to a wide range of crystalline powders in order to modulate the performance of Class II and IV raw materials [2][3][4]. Since then, the process of reducing particle size to increase the surface area [5][6][7], as well as obtaining salts [4,8,9], nanocrystals [10,11], cocrystals [12,13], and eutectic mixtures [14][15][16] were some of the approaches that have been explored. Saquinavir base (SQV) (Figure 1) is an anti-HIV drug which belongs to Class II in the BCS.…”

Section: Introductionmentioning

confidence: 99%

Saquinavir-Piperine Eutectic Mixture: Preparation, Characterization, and Dissolution Profile

Fandaruff,

Quirós-Fallas,

Vega-Baudrit

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

The dissolution rate of the anti-HIV drug saquinavir base (SQV), a poorly water-soluble and extremely low absolute bioavailability drug, was improved through a eutectic mixture formation approach. A screening based on a liquid-assisted grinding technique was performed using a 1:1 molar ratio of the drug and the coformers sodium saccharinate, theobromine, nicotinic acid, nicotinamide, vanillin, vanillic acid, and piperine (PIP), followed by differential scanning calorimetry (DSC). Given that SQV-PIP was the only resulting eutectic system from the screening, both the binary phase and the Tammann diagrams were adapted to this system using DSC data of mixtures prepared from 0.1 to 1.0 molar ratios in order to determine the exact eutectic composition. The SQV-PIP system formed a eutectic at a composition of 0.6 and 0.40, respectively. Then, a solid-state characterization through DSC, powder X-ray diffraction (PXRD), including small-angle X-ray scattering (SAXS) measurements to explore the small-angle region in detail, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a powder dissolution test were performed. The conventional PXRD analyses suggested that the eutectic mixture did not exhibit structural changes; however, the small-angle region explored through the SAXS instrument revealed a change in the crystal structure of one of their components. FT-IR spectra showed no molecular interaction in the solid state. Finally, the dissolution profile of SQV in the eutectic mixture was different from the dissolution of pure SQV. After 45 min, approximately 55% of the drug in the eutectic mixture was dissolved, while, for pure SQV, 42% dissolved within this time. Hence, this study concludes that the dissolution rate of SQV can be effectively improved through the approach of using PIP as a coformer.

show abstract

The Effect of the Particle Size Reduction on the Biorelevant Solubility and Dissolution of Poorly Soluble Drugs with Different Acid-Base Character

Cited by 10 publications

References 30 publications

Modified Curcuminoid-Rich Extract Liposomal CRE-SDInhibits Osteoclastogenesis via the Canonical NF-κB Signaling Pathway

Modified Curcuminoid-Rich Extract Liposomal CRE-SDInhibits Osteoclastogenesis via the Canonical NF-κB Signaling Pathway

Composition and Technology Development for Obtaining Amorphous Solid Dispersion of Ebastine by Hot Melt Extrusion to Increase Dissolution Rate

Saquinavir-Piperine Eutectic Mixture: Preparation, Characterization, and Dissolution Profile

Contact Info

Product

Resources

About