Microstructured ternary solid dispersions to improve carbamazepine solubility

Martins, Ronei Ximenes; Siqueira, Sílvia Regina Dowgan Tesseroli de; Tacon, Luciana A.; Freitas, Luís Alexandre Pedro de

doi:10.1016/j.powtec.2011.09.041

Cited by 35 publications

(20 citation statements)

References 40 publications

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“…CBZ is traditionally given as a solid dosage or suspensions form by oral administration, but due to its poor solubility in water (120 µg/mL, 500 µM, at 25 °C) (Brewster et al, 1990;Hemenway et al, 2009;Martins et al, 2012), it has a slow and irregular gastrointestinal absorption, leading to an incomplete drug bioavailability (El-Zein et al, 1998;Gavini et al, 2006;Kobayashi et al, 2000). In addition, this reduced solubility does not allow its incorporation in therapeutic dosages in aqueous solutions for intravenous injection (Serralheiro et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Igartúa

Martínez

Temprana

et al. 2018

International Journal of Pharmaceutics

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Carbamazepine (CBZ) is an antiepileptic drug, which also could be used in the treatment of neurodegenerative diseases, such as the Alzheimer's disease. However, its use has been limited due to its low solubility, inefficient pharmacokinetic profiles, and multiple side effects. PAMAM dendrimers, ethylenediamine core, generation 4.0 (amine terminal groups) and 4.5 (carboxylate terminal groups) (DG4.0 and DG4.5 respectively) are polymers that can increase drug solubility through complexation. Thus, the aim of this work was to obtain and characterize complexes between CBZ and dendrimers. Both DG4.0 and DG4.5 allowed the incorporation of ∼20 molecules of CBZ per dendrimer, into their hydrophobic pockets. DG4.0-CBZ and DG4.5-CBZ complexes were found to be stable for 90 days at 37 °C and resistant to a lyophilization process, presenting controlled drug release. Also, the complexes nanotoxicity was tested ex vivo (human red blood cells), in vitro (N2a cell line), and in vivo (zebrafish). No hemolytic effect was observed in the ex vivo model. As regards in vitro toxicity, the DG4.5-CBZ complexes significantly reduced the toxicity caused by the free drug. Moreover, the DG4.5-CBZ did not cause neurotoxicity or cardiotoxicity in zebrafish larvae. In conclusion, a stable and biocompatible drug delivery system based on the DG4.5 capable of complex the CBZ has been developed. This achievement highlights the advantages of using negatively charged dendrimers for nanomedicine.

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Section: Introductionmentioning

confidence: 99%

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Igartúa

Martínez

Temprana

et al. 2018

International Journal of Pharmaceutics

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“…Nowadays, all of the generic drug manufacturers are competing in the increasingly sophisticated market. The improvement of the drug solubility will dramatically draw their attention as this can make profit towards their business [8]. Hence, the crystal form of APIs is selected to fulfill the requirement.…”

Section: Introductionmentioning

confidence: 99%

Carbamazepine-Fumaric Acid and Carbamazepine-Succinic Acid Co-crystal Screening Using Solution Based Method

Rahman¹,

Rahim²,

Chou³

et al. 2017

IJCEA

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Abstract-Co-crystal plays a critical role in the pharmaceutical industry and becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ) and co-crystal former (CCF) of fumaric acid (FUM) and succinic acid (SA) using non-stoichiometric method (addition of CBZ to CCF saturated solution) and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF) in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared (FT-IR). The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method for CBZ-FUM system and in all methods for CBZ-SA system. The findings from this analysis revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvents systems. DSC analysis had shown that the melting point of CBZ-FUM and CBZ-SA co-crystals were in the range similar to the previous study. The characterization using FT-IR indicated that the functional groups which include amides and carboxylic acids were presented in the co-crystal produced. Further study on the co-crystal solubility and dissolution rate is needed in order to access the efficacy of the co-crystal since the screening methods have been successfully confirmed the formation of the co-crystal.

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“…Increased agglomeration at higher inlet temperature has also been hypothesized to cause an increase in particle size. A higher drying temperature leads to a quicker drying due to more heat transfer into the drying droplet 55 . This has two effects on the fate of the droplet.…”

Section: Inlet and Outlet Temperaturesmentioning

confidence: 99%

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2017

IJPSR

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ABSTRACT:As time passes more and more poorly water soluble drug are being discovered. Formulating these drugs in to amorphous solid dispersion is an effective strategy to deliver poorly water soluble drugs. Spray drying is one of common and a well-established manufacturing technique which can be used to formulate amorphous solid dispersions (ASDs). However, the spray drying is complex phenomenon and the spray drying process parameters yield the ASD with specific characteristics. Various diverse factors interact in an inter-dependent manner to determine the final product properties. This review discusses the basic background of spray drying, and various aspects of spray drying such as instrumentation, thermodynamics, drying kinetics, particle formation process and scale-up challenges are included. Recent advances in the spray-based drying techniques are mentioned along with some future avenues where major research is needed.

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Microstructured ternary solid dispersions to improve carbamazepine solubility

Cited by 35 publications

References 40 publications

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Carbamazepine-Fumaric Acid and Carbamazepine-Succinic Acid Co-crystal Screening Using Solution Based Method

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