Change search
ReferencesLink to record
Permanent link

Direct link
Effect of DMSO on micellization, gelation and drug release profile of poloxamer 407
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
2010 (English)In: Internation Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 394, no 1-2, 92-98 p.Article in journal (Refereed) Published
Abstract [en]

The application of many recently developed or approved drugs and pharmaceuticals is seriously hampered by their low solubility in aqueous media. Hence, numerous promising pharmaceutical delivery systems (including novel "smart" systems based on poloxamer gels, which have highly advantageous thermo-reversible characteristics and low toxicity) cannot solubilize required doses of various drugs without additives such as co-solvents or salts. Therefore, we have studied the effects of dimethyl sulphoxide (DMSO)-a commonly used co-solvent during drug development stages-on the micellization, gelation and dissolution properties of aqueous poloxamer solutions. Differential scanning calorimetry and tube inversion experiments clearly showed that DMSO induces reductions in the critical micellization and gelation temperatures of poloxamer systems. In addition, high resolution solid state 1H Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) analyses provided indications of the specific chemical groups in the poloxamer affected by DMSO, and the molecular mechanism involved. The presence of DMSO accelerated dissolution of the pure gel in water and the release of a hydrophobic drug (flufenamic acid) from poloxamer gel, while it reduced the release of a hydrophilic drug (metoprolol tartrate).

Place, publisher, year, edition, pages
Elsevier B.V. , 2010. Vol. 394, no 1-2, 92-98 p.
Keyword [en]
Poloxamer, Drug delivery, Micellization, DMSO, Calorimetry, NMR
URN: urn:nbn:se:umu:diva-34638DOI: 10.1016/j.ijpharm.2010.05.012ISI: 000279720400011PubMedID: 20472044OAI: diva2:323277
Available from: 2010-06-10 Created: 2010-06-10 Last updated: 2011-04-08Bibliographically approved
In thesis
1. Controlled release gel formulations and preclinical screening of drug candidates
Open this publication in new window or tab >>Controlled release gel formulations and preclinical screening of drug candidates
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Simple gel formulations may be applied to enhance the systemic and local exposure of potential compounds. The aim of this thesis is the development and characterization of controlled release formulations based on thermo-reversible poloxamer gels, which are suitable for novel drug delivery applications.  In particular co-solvents (DMSO, ethanol), mucoadhesive polymers (chitosan, alginate) and salts (sodium tripolyphosphate, CaCl2) have been used to enhance the applications of poloxamer 407 (P407) formulations in preclinical animal studies. The impact of these additives on the micellization and gelation properties of P407 aqueous solutions was studied by calorimetric methods, nuclear magnetic resonance spectroscopy (NMR) and “tube inversion” experiments. The drug release behavior of hydrophobic and hydrophilic drugs was characterized by using a membrane/membrane-free experimental setup. Finally, preliminary pharmacokinetic studies using a mouse model were conducted for screening of selected inhibitors of bacterial type III secretion and for evaluation of different formulations including P407 gel. All additives, used here, reduced the CMTs (critical micelle temperature) of dilute P407 solutions, with the exception of ethanol. The gelation temperature of concentrated P407 solutions was lowered in the presence of CaCl2, DMSO, TPP and alginate. 1H MAS (Magic Angle Spinning) NMR studies revealed that DMSO influences the hydrophobicity of the PPO segment of P407 polymers. Low concentrations of DMSO did not show any major effect on the drug release from P407 gels and may be used to improve the exposure of lead compounds in poloxamer gels. A newly developed in situ ionotropic gelation of chitosan in combination with TPP in P407 gels showed an enhanced resistance to water and reduced the release rates of model drugs. From preliminary pharmacokinetic studies in mice it was revealed that poloxamer formulations resulted in an increased plasma half-life of the lead compound.

Place, publisher, year, edition, pages
Umeå: Department of Chemistry, 2011. 51 p.
poloxamer, drug delivery, micellization, DMSO, calorimetry, NMR. in situ gelation, chitosan, preclinical pharmacokinetics, type III secretion inhibitors
National Category
Physical Chemistry
Research subject
urn:nbn:se:umu:diva-40489 (URN)978-91-7459-161-3 (ISBN)
Public defence
2011-03-22, KBC-huset, KB3A9, Umeå universitet, Umeå, 10:00 (English)
Available from: 2011-03-01 Created: 2011-02-23 Last updated: 2011-03-01Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Ur-Rehman, TofeeqTavelin, StaffanGröbner, Gerhard
By organisation
Department of ChemistryClinical Pharmacology
In the same journal
Internation Journal of Pharmaceutics

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 161 hits
ReferencesLink to record
Permanent link

Direct link