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Molecular dynamics and aggregation behaviour in aqueous polymer-drug model systems
-
- Evertsson, Hans (författare)
- Uppsala universitet,Institutionen för farmaceutisk kemi
- (creator_code:org_t)
- ISBN 9155444709
- Uppsala : Acta Universitatis Upsaliensis, 1999
- Engelska 39 s.
- Serie: Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 0282-7484 ; 205
- Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract
Ämnesord
Stäng
- Pharmaceutical formulations often contain polymers used as binders, swelling agents, etc., to give the formulation mechanical stability or specific drug release features. Many drug substances, as well as polymers, are amphiphilic which will give an associative polymer-drug interaction, affecting the dissolution rate and drug release. This thesis focuses on the molecular dynamics of model nonionic polymer-anionic drug complexesformed in aqueous solution. Two low molecular weight amphiphiles with different surface activities are used; the surfactant sodium dodecyl sulfate (SDS) and the sodium salt of ibuprofen. The polymers studied are a set of cellulose ethers of different hydrophobicity, with special emphasis on ethyl(hydroxyethyl)cellulose (EHEC).Fluorescence probe techniques and nuclear magnetic resonance (NMR) are the main methods used. The molecular dynamics of the EHEC/SDS system is strongly composition dependent. Mixed EHEC/SDS micelles with low SDS aggregation numbers and a high relative content of EHEC is more than three times as rigid as mixed micelles with a high relative content of SDS, as monitored by the fluorescent probe 1,3-di(1-pyrenyl)propane(P3P) and 1H NMR transverse relaxation.The microviscosities as monitored by P3P of a set of ten cellulose ethers with different hydrophobicity, interacting with SDS, are compared. A correlation between the microviscosity and the polymer-SDS interaction energy, as qualitatively estimated from the SDS concentration at onset of polymer-SDS association, is found. This correlation is further described by principal component analysis for a subset of six EHEC samples. The microviscosity of mixed polymer-SDS micelles as monitored by P3P is found to be a valuable parameter for the characterization of polymer samples, and can be used to predict the surface tension of the polymer.The interaction between EHEC and the sodium salt of ibuprofen resembles the normally accepted model for polymer-surfactant interaction, but is more complex. Fluorescence probe- and pulsed gradient spin echo self diffusion NMR- (PGSE-NMR) measurements indicate that premicellar aggregates of ibuprofen adsorb onto EHEC below the onset of cooperative adsorption with respect to the ibuprofen concentration. The thesis shows theimportance of detailed knowledge of the molecular dynamics for design of controlled release preparations.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Nyckelord
- Pharmaceutical chemistry
- Farmaceutisk kemi
- Pharmaceutical chemistry
- Farmaceutisk kemi
- Physical and Inorganic Pharmaceutical Chemistry
- fysikalisk och oorganisk farmaceutisk kemi
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
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