Cyclodextrins: efficient biocompatible solubilizing excipients for bromhexine liquid and semi-solid drug delivery systems

Research output: Contribution to journalJournal articlepeer-review

Standard

Cyclodextrins : efficient biocompatible solubilizing excipients for bromhexine liquid and semi-solid drug delivery systems. / Stojanov, Mladen; Nielsen, Hanne Mørck; Larsen, Kim Lambertsen.

In: International Journal of Pharmaceutics, Vol. 422, No. 1-2, 2012, p. 349-355.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Stojanov, M, Nielsen, HM & Larsen, KL 2012, 'Cyclodextrins: efficient biocompatible solubilizing excipients for bromhexine liquid and semi-solid drug delivery systems', International Journal of Pharmaceutics, vol. 422, no. 1-2, pp. 349-355. https://doi.org/10.1016/j.ijpharm.2011.10.023

APA

Stojanov, M., Nielsen, H. M., & Larsen, K. L. (2012). Cyclodextrins: efficient biocompatible solubilizing excipients for bromhexine liquid and semi-solid drug delivery systems. International Journal of Pharmaceutics, 422(1-2), 349-355. https://doi.org/10.1016/j.ijpharm.2011.10.023

Vancouver

Stojanov M, Nielsen HM, Larsen KL. Cyclodextrins: efficient biocompatible solubilizing excipients for bromhexine liquid and semi-solid drug delivery systems. International Journal of Pharmaceutics. 2012;422(1-2):349-355. https://doi.org/10.1016/j.ijpharm.2011.10.023

Author

Stojanov, Mladen ; Nielsen, Hanne Mørck ; Larsen, Kim Lambertsen. / Cyclodextrins : efficient biocompatible solubilizing excipients for bromhexine liquid and semi-solid drug delivery systems. In: International Journal of Pharmaceutics. 2012 ; Vol. 422, No. 1-2. pp. 349-355.

Bibtex

@article{b2a9e5632ca543e6827b2ac97e8a0dc8,
title = "Cyclodextrins: efficient biocompatible solubilizing excipients for bromhexine liquid and semi-solid drug delivery systems",
abstract = "Bromhexine hydrochloride (bromhexine) is a mucolytic agent with very low aqueous solubility. However, with addition of cyclodextrins (CD) to the formulation, this disadvantage may be limited and therapeutic doses of bromhexine in solution can be achieved.The interaction of bromhexine with α-, β-, γ- and sulfobutylether (SBE)-β-CD, respectively, was elucidated by means of phase solubility diagrams and calorimetric analysis. The complexes were further characterized by size, and the effect of the CD concentrations used was evaluated in a viability assay.From phase solubility diagrams with α-, β-, γ- and SBE-β-CD and bromhexine, it was determined that the solubility of bromhexine significantly increased with addition of CDs, showing an AL type solubility curve for bromhexine/α- and β-CD, and an AN type for bromhexine/γ- and SBE-β-CD. The highest soluble concentrations of bromhexine were achieved with α- and SBE-β-CD, i.e. when using a 100 mM α- or SBE-β-CD solution, 4 and 5.5 times more bromhexine was solubilized, respectively, compared to pure aqueous solubilization of bromhexine. The apparent association constants determined from the phase solubility studies showed very low values of 34, 17, 8 and 156 M−1 for bromhexine/α-, β-, γ- and SBE-β-CD, respectively, as compared to the association constants determined by ITC which exhibited values of 89, 307 and 1680 M−1 for bromhexine/α-, β- and SBE-β-CD, respectively. The formation of aggregates aided solubilization of bromhexine in the phase solubility studies explaining the difference in the association constants between the two methods. Due to very low signal to noise ratio, no information was extracted for bromhexine/γ-CD solutions from the ITC measurements. The effect on cellular viability of the CDs ranked β- > α- > SBE-β- > γ-CD. In conclusion, the results altogether demonstrated that SBE-β-CD is the most suitable CD for future drug delivery systems from the aspect of high amounts of solubilized bromhexine and high safety of the SBE-β-CD.",
author = "Mladen Stojanov and Nielsen, {Hanne M{\o}rck} and Larsen, {Kim Lambertsen}",
year = "2012",
doi = "10.1016/j.ijpharm.2011.10.023",
language = "English",
volume = "422",
pages = "349--355",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1-2",

}

RIS

TY - JOUR

T1 - Cyclodextrins

T2 - efficient biocompatible solubilizing excipients for bromhexine liquid and semi-solid drug delivery systems

AU - Stojanov, Mladen

AU - Nielsen, Hanne Mørck

AU - Larsen, Kim Lambertsen

PY - 2012

Y1 - 2012

N2 - Bromhexine hydrochloride (bromhexine) is a mucolytic agent with very low aqueous solubility. However, with addition of cyclodextrins (CD) to the formulation, this disadvantage may be limited and therapeutic doses of bromhexine in solution can be achieved.The interaction of bromhexine with α-, β-, γ- and sulfobutylether (SBE)-β-CD, respectively, was elucidated by means of phase solubility diagrams and calorimetric analysis. The complexes were further characterized by size, and the effect of the CD concentrations used was evaluated in a viability assay.From phase solubility diagrams with α-, β-, γ- and SBE-β-CD and bromhexine, it was determined that the solubility of bromhexine significantly increased with addition of CDs, showing an AL type solubility curve for bromhexine/α- and β-CD, and an AN type for bromhexine/γ- and SBE-β-CD. The highest soluble concentrations of bromhexine were achieved with α- and SBE-β-CD, i.e. when using a 100 mM α- or SBE-β-CD solution, 4 and 5.5 times more bromhexine was solubilized, respectively, compared to pure aqueous solubilization of bromhexine. The apparent association constants determined from the phase solubility studies showed very low values of 34, 17, 8 and 156 M−1 for bromhexine/α-, β-, γ- and SBE-β-CD, respectively, as compared to the association constants determined by ITC which exhibited values of 89, 307 and 1680 M−1 for bromhexine/α-, β- and SBE-β-CD, respectively. The formation of aggregates aided solubilization of bromhexine in the phase solubility studies explaining the difference in the association constants between the two methods. Due to very low signal to noise ratio, no information was extracted for bromhexine/γ-CD solutions from the ITC measurements. The effect on cellular viability of the CDs ranked β- > α- > SBE-β- > γ-CD. In conclusion, the results altogether demonstrated that SBE-β-CD is the most suitable CD for future drug delivery systems from the aspect of high amounts of solubilized bromhexine and high safety of the SBE-β-CD.

AB - Bromhexine hydrochloride (bromhexine) is a mucolytic agent with very low aqueous solubility. However, with addition of cyclodextrins (CD) to the formulation, this disadvantage may be limited and therapeutic doses of bromhexine in solution can be achieved.The interaction of bromhexine with α-, β-, γ- and sulfobutylether (SBE)-β-CD, respectively, was elucidated by means of phase solubility diagrams and calorimetric analysis. The complexes were further characterized by size, and the effect of the CD concentrations used was evaluated in a viability assay.From phase solubility diagrams with α-, β-, γ- and SBE-β-CD and bromhexine, it was determined that the solubility of bromhexine significantly increased with addition of CDs, showing an AL type solubility curve for bromhexine/α- and β-CD, and an AN type for bromhexine/γ- and SBE-β-CD. The highest soluble concentrations of bromhexine were achieved with α- and SBE-β-CD, i.e. when using a 100 mM α- or SBE-β-CD solution, 4 and 5.5 times more bromhexine was solubilized, respectively, compared to pure aqueous solubilization of bromhexine. The apparent association constants determined from the phase solubility studies showed very low values of 34, 17, 8 and 156 M−1 for bromhexine/α-, β-, γ- and SBE-β-CD, respectively, as compared to the association constants determined by ITC which exhibited values of 89, 307 and 1680 M−1 for bromhexine/α-, β- and SBE-β-CD, respectively. The formation of aggregates aided solubilization of bromhexine in the phase solubility studies explaining the difference in the association constants between the two methods. Due to very low signal to noise ratio, no information was extracted for bromhexine/γ-CD solutions from the ITC measurements. The effect on cellular viability of the CDs ranked β- > α- > SBE-β- > γ-CD. In conclusion, the results altogether demonstrated that SBE-β-CD is the most suitable CD for future drug delivery systems from the aspect of high amounts of solubilized bromhexine and high safety of the SBE-β-CD.

U2 - 10.1016/j.ijpharm.2011.10.023

DO - 10.1016/j.ijpharm.2011.10.023

M3 - Journal article

VL - 422

SP - 349

EP - 355

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -

ID: 36144754