Micronization of N -acetylcysteine by supercritical fluid: Evaluation of in vitro and in vivo biological activity

Aguiar, Gean Pablo S.; Marcon, Matheus; Mocelin, Ricieri; Herrmann, Ana Paula; Chaves, Lorenzo M.P.C.; Piato, Ângelo; Lanza, Marcelo; Oliveira, J. Vladimir

doi:10.1016/j.supflu.2017.06.010

Cited by 22 publications

(23 citation statements)

References 41 publications

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“…To date, the classical approach for increasing the dissolution rate of poorly soluble drugs is to reduce particle size, in particular through micronization [ 3 ]. However, it seems that further improvement in the drug dissolution rate and thus in bioavailability demands a shifting from micronization to nanonization.…”

Section: Introductionmentioning

confidence: 99%

“…Among the advantages, there are: Possibility of administering a drug through different administration routes (oral, intravenous, intramuscular, pulmonary, ocular, dermal) [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]; Possibility of formulating a drug under different pharmaceutical dosage forms (tablets, capsules, suspensions, ointments, etc.) [ 17 , 25 , 26 , 27 , 28 , 29 ]; Higher solubility (thermodynamic or kinetic depending on the solid physical state of the drug) than conventional particles [ 8 , 17 , 22 , 23 , 30 , 31 , 32 ]; Faster dissolution rate than conventional particles [ 3 , 8 , 9 , 16 , 30 , 33 , 34 , 35 ]; Long circulating nanocrystals [ 36 , 37 , …”

Section: Introductionmentioning

confidence: 99%

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Nanocrystals of Poorly Soluble Drugs: Drug Bioavailability and Physicochemical Stability

et al. 2018

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Many approaches have been developed over time to overcome the bioavailability limitations of poorly soluble drugs. With the advances in nanotechnology in recent decades, science and industry have been approaching this issue through the formulation of drugs as nanocrystals, which consist of “pure drugs and a minimum of surface active agents required for stabilization”. They are defined as “carrier-free submicron colloidal drug delivery systems with a mean particle size in the nanometer range, typically between 10–800 nm”. The primary importance of these nanoparticles was the reduction of particle size to nanoscale dimensions, with an increase in the particle surface area in contact with the dissolution medium, and thus in bioavailability. This approach has been proven successful, as demonstrated by the number of such drug products on the market. Nonetheless, despite the definition that indicates nanocrystals as a “carrier-free” system, surface active agents are necessary to prevent colloidal particles aggregation and thus improve stability. In addition, in more recent years, nanocrystal properties and technologies have attracted the interest of researchers as a means to obtain colloidal particles with modified biological properties, and thus their interest is now also addressed to modify the drug delivery and targeting. The present work provides an overview of the achievements in improving the bioavailability of poorly soluble drugs according to their administration route, describes the methods developed to overcome physicochemical and stability-related problems, and in particular reviews different stabilizers and surface agents that are able to modify the drug delivery and targeting.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanocrystals of Poorly Soluble Drugs: Drug Bioavailability and Physicochemical Stability

et al. 2018

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“…Changes in the melting point were also observed by Aguiar et al . when studying n-acetylcysteine (NAC) micronization with the SEDS technique 15 . In that work, in vivo evaluation of the micronized versus non-micronized compounds showed that micronized NAC exhibited a similar biological activity even at a concentration 100-fold lower than the non-micronized NAC.…”

Section: Discussionmentioning

confidence: 99%

“…Drug bioavailability can be improved by micronizing the raw material by applying the supercritical carbon dioxide micronization technology 15 , 16 . Supercritical carbon dioxide is a suitable green chemistry technique to prepare and modify material properties (Fig.…”

Section: Introductionmentioning

confidence: 99%

Micronization potentiates curcumin’s anti-seizure effect and brings an important advance in epilepsy treatment

Bertoncello

Aguiar

Oliveira

et al. 2018

Sci Rep

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Epilepsy is one of the most common neurological diseases, and current antiepileptic drugs fail to suppress seizure occurrence in around one third of epileptic patients. Curcumin is a phytochemical with promising effects on epilepsy treatment. However, its application has been hindered by its low bioavailability. In order to improve curcumin’s anti-seizure properties, increasing its bioavailability, here we proposed to micronize the compound through supercritical carbon dioxide processing, a suitable green chemistry technique to prepare and modify material properties. Here we investigated the anti-seizure potential of the classical antiepileptic drug valproate, curcumin in its natural state, and micronized curcumin in a PTZ-induced seizure model in zebrafish (Danio rerio). Concerning seizure development, valproate, curcumin and micronized curcumin showed protective effects, slowing seizure development both in larvae and adult animals. Nevertheless, considering the occurrence of the tonic-clonic seizure stage, only valproate and micronized curcumin reduced it, both in larvae and adult zebrafish, unlike non-processed curcumin. Our obtained results are very promising, since micronized curcumin showed effects that are similar to a classic antiepileptic drug, reducing seizure occurrence and slowing seizure progression.

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“…Briefly, the experimental apparatus consists of a high pressure vessel used as precipitation chamber with internal volume of 600 mL and internal diameter of 8 cm; two syringe pumps for CO 2 displacement (ISCO, Model 500D), operated independently by a set of ball valves (Swagelok, Model SS-83KS4), and a digital HPLC liquid pump (Acuflow, Series III) used for organic solution delivery. A schematic diagram of the processing apparatus was recently presented by Aguiar et al (2017) and Dal Magro et al 2017.…”

Section: Solution Enhanced Dispersion By Supercritical Fluids Techniquementioning

confidence: 99%

Poly(hydroxybutyrate-Co-Hydroxyvalerate) Micronization by Solution Enhanced Dispersion by Supercritical Fluids Technique

Aguiar

Magro

Oliveira

et al. 2018

Braz. J. Chem. Eng.

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Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a biodegradable polymer used for a wide range of applications, especially in biomedical and food industry, for which bioactive compound encapsulation is noteworthy. This work aimed to micronize PHBV by Solution Enhanced Dispersion by Supercritical Fluids technique and evaluate possible changes in polymer crystallinity. A 2 3 Central Composite Design with 3 central points was used to analyze the influence of pressure, temperature and PHBV concentration on particle size produced. Micronized particles were mostly spherical with sizes from 210 to 720 nm, and free of organic solvents. PHBV crystallinity degree was approximately 20% higher when polymer was processed at 8 MPa compared to that processed at 10 and 12 MPa, as well as to the raw polymer. Results suggest versatility in PHBV application according to SEDS process parameters and the possibility of its use in drug delivery systems.

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Micronization of N -acetylcysteine by supercritical fluid: Evaluation of in vitro and in vivo biological activity

Cited by 22 publications

References 41 publications

Nanocrystals of Poorly Soluble Drugs: Drug Bioavailability and Physicochemical Stability

Nanocrystals of Poorly Soluble Drugs: Drug Bioavailability and Physicochemical Stability

Micronization potentiates curcumin’s anti-seizure effect and brings an important advance in epilepsy treatment

Poly(hydroxybutyrate-Co-Hydroxyvalerate) Micronization by Solution Enhanced Dispersion by Supercritical Fluids Technique

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