Interaction of Native Cyclodextrins and Their Hydroxypropylated Derivatives with Carbamazepine in Aqueous Solution. Evaluation of Inclusion Complexes and Aggregates Formation

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2019 Aug 29

PMID 31459413

Citations 6

Authors

Andre Rodrigues Sa Couto

Alexey Ryzhakov

Kim Lambertsen Larsen

Thorsteinn Loftsson

Affiliations

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Abstract

A detailed comprehensive study on how the formation of soluble and insoluble carbamazepine/cyclodextrins (CBZ/CD) complexes (with consequent changes in the solid-phase composition) depends on the CD structure is not yet available. Moreover, the study of possible influence of this drug on the tendency of CDs and their complexes to self-aggregate is still lacking. Phase-solubility studies demonstrated that CDs and CBZ form a range of soluble (A-type: αCD, βCD, and hydroxypropylated CDs) and insoluble (B-type: γCD) complexes depending on CD used. HPβCD proved to be the best CD solubilizer for CBZ forming the most stable complex with highest apparent solubility, whereas γCD was shown to be the best native CD. For the native CDs, CBZ solubilization increases with increasing CD cavity diameter (αCD ≪ βCD < γCD). Solid phases collected from phase-solubility studies were characterized by Fourier-transformed infrared spectroscopy, differential scanning calorimetry, and X-ray powder diffraction to elucidate their composition and crystalline structure. They provided similar conclusions being overall supportive of phase-solubility, osmolality, and permeation studies results. Solid CBZ was the only detected component for A-type profiles over the CD concentration range studied, whereas precipitation of poorly soluble CBZ/γCD complexes (B-type) was observed (i.e., at and beyond plateau region). Osmometry and permeation studies were applied to evaluate the effect of CBZ on the aggregate formation and also to elucidate their influence on CD complex solubility and permeation profile. Permeation method was shown to be the most effective method to detect and evaluate aggregate formation in aqueous γCD and HPβCD solutions containing CBZ. CBZ did not affect the HPβCD tendency to self-aggregate but CBZ did modify the aggregation behavior of γCD decreasing the apparent critical aggregation concentration value from 4.2% (w/v) (in pure aqueous γCD solution) to 2.5% (w/v) (when CBZ was present).

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References

Rustichelli C, Gamberini G, Ferioli V, Gamberini M, Ficarra R, Tommasini S . Solid-state study of polymorphic drugs: carbamazepine. J Pharm Biomed Anal. 2000; 23(1):41-54. DOI: 10.1016/s0731-7085(00)00262-4. View

Loftsson T, Magnusdottir A, Masson M, Sigurjonsdottir J . Self-association and cyclodextrin solubilization of drugs. J Pharm Sci. 2002; 91(11):2307-16. DOI: 10.1002/jps.10226. View

Koester L, Xavier C, Mayorga P, Bassani V . Influence of beta-cyclodextrin complexation on carbamazepine release from hydroxypropyl methylcellulose matrix tablets. Eur J Pharm Biopharm. 2003; 55(1):85-91. DOI: 10.1016/s0939-6411(02)00127-3. View

Koester L, Mayorga P, Pereira V, Petzhold C, Bassani V . Carbamazepine/betaCD/HPMC solid dispersions. II. Physical characterization. Drug Dev Ind Pharm. 2003; 29(2):145-54. DOI: 10.1081/ddc-120016722. View

Loftsson T, Masson M, Brewster M . Self-association of cyclodextrins and cyclodextrin complexes. J Pharm Sci. 2004; 93(5):1091-9. DOI: 10.1002/jps.20047. View

Smith J, Macrae R, Snowden M . Effect of SBE7-beta-cyclodextrin complexation on carbamazepine release from sustained release beads. Eur J Pharm Biopharm. 2005; 60(1):73-80. DOI: 10.1016/j.ejpb.2004.12.001. View

Loftsson T, Hreinsdottir D, Masson M . Evaluation of cyclodextrin solubilization of drugs. Int J Pharm. 2005; 302(1-2):18-28. DOI: 10.1016/j.ijpharm.2005.05.042. View

Loftsson T, Jarho P, Masson M, Jarvinen T . Cyclodextrins in drug delivery. Expert Opin Drug Deliv. 2005; 2(2):335-51. DOI: 10.1517/17425247.2.1.335. View

Wu A, Shen X, He Y . Investigation on gamma-cyclodextrin nanotube induced by N,N'-diphenylbenzidine molecule. J Colloid Interface Sci. 2005; 297(2):525-33. DOI: 10.1016/j.jcis.2005.11.014. View

10.

Loftsson T, Duchene D . Cyclodextrins and their pharmaceutical applications. Int J Pharm. 2006; 329(1-2):1-11. DOI: 10.1016/j.ijpharm.2006.10.044. View

11.

Brewster M, Loftsson T . Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007; 59(7):645-66. DOI: 10.1016/j.addr.2007.05.012. View

12.

Brewster M, Anderson W, Estes K, Bodor N . Development of aqueous parenteral formulations for carbamazepine through the use of modified cyclodextrins. J Pharm Sci. 1991; 80(4):380-3. DOI: 10.1002/jps.2600800420. View

13.

Kou W, Cai C, Xu S, Wang H, Liu J, Yang D . In vitro and in vivo evaluation of novel immediate release carbamazepine tablets: complexation with hydroxypropyl-β-cyclodextrin in the presence of HPMC. Int J Pharm. 2011; 409(1-2):75-80. DOI: 10.1016/j.ijpharm.2011.02.042. View

14.

Jain A, Date A, Pissurlenkar R, Coutinho E, Nagarsenker M . Sulfobutyl ether(7) β-cyclodextrin (SBE(7) β-CD) carbamazepine complex: preparation, characterization, molecular modeling, and evaluation of in vivo anti-epileptic activity. AAPS PharmSciTech. 2011; 12(4):1163-75. PMC: 3225538. DOI: 10.1208/s12249-011-9685-z. View

15.

Crini G . Review: a history of cyclodextrins. Chem Rev. 2014; 114(21):10940-75. DOI: 10.1021/cr500081p. View

16.

Medarevic D, Kachrimanis K, Djuric Z, Ibric S . Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-β-cyclodextrin. Eur J Pharm Sci. 2015; 78:273-85. DOI: 10.1016/j.ejps.2015.08.001. View

17.

Ryzhakov A, Do Thi T, Stappaerts J, Bertoletti L, Kimpe K, Rodrigues Sa Couto A . Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions. J Pharm Sci. 2016; 105(9):2556-2569. DOI: 10.1016/j.xphs.2016.01.019. View

18.

Stappaerts J, Do Thi T, Dominguez-Vega E, Somsen G, Van den Mooter G, Augustijns P . The impact of guest compounds on cyclodextrin aggregation behavior: A series of structurally related parabens. Int J Pharm. 2017; 529(1-2):442-450. DOI: 10.1016/j.ijpharm.2017.07.026. View

19.

Jansook P, Ogawa N, Loftsson T . Cyclodextrins: structure, physicochemical properties and pharmaceutical applications. Int J Pharm. 2017; 535(1-2):272-284. DOI: 10.1016/j.ijpharm.2017.11.018. View

20.

Rodrigues Sa Couto A, Ryzhakov A, Loftsson T . Self-Assembly of α-Cyclodextrin and β-Cyclodextrin: Identification and Development of Analytical Techniques. J Pharm Sci. 2018; 107(8):2208-2215. DOI: 10.1016/j.xphs.2018.03.028. View