Drug delivery to nasal or ocular mucosa for either local or systemic action faces many obstacles – these routes are protected by effective mechanisms. Gel formulations with suitable rheological and mucoadhesive properties increase the contact time at the site of absorption. However, drug release from the gel must be sustained if benefits are to be gained from the prolonged contact time.The work presented here is the characterization of gels and the determination of the mucoadhesive properties of polymers using rheology. Gelrite gels were formed in simulated tear fluid at concentrations of polymer as low as 0.1%, and it was shown that sodium was the most important gel-promoting ion in vivo. Rheology, although it may be a questionable technique for evaluating mucoadhesive properties of polymers, showed that interactions between mucin and polymers were most likely to be seen with weak gels.It was possible to control the release of uncharged drug substances by including surfactants that form micelles in the gel. This release depended on lipophilic interactions between the drug and the polymer and/or the micelles. Controlled-release formulations of charged drugs could be designed by mixing the drugs with oppositely charged surfactants in certain ratios. In this way, vesicles in which the drug and surfactant constituted the bilayer formed spontaneously. The vesicle formation was affected by the presence of polymer, and very small vesicles that gave a slow release rate were formed when a lipophilically modified polymer was used.The gels were also evaluated in the Using chamber using porcine nasal mucosa…
Contents
1. INTRODUCTION
2. AIMS
3. MATERIALS AND METHODS
3.1 Materials
3.1.1 Drugs, model substances and radiolabelled markers 12
3.1.2 Polymers
3.1.3 Surfactants
3.1.4 Other chemicals
3.2 Preparation of samples
3.2.1 Preparation of Carbopol gels
3.2.2 Preparation of Gelrite gels
3.2.3 Mucin mixtures
3.3 Rheology
3.3.1 Temperature scans
3.3.2 Evaluation of mucoadhesion
3.4 Determination of micellar partition coefficient
3.5 Drug release measurements and diffusion coefficient calculation 16
3.6 Cryo-TEM and surface tension measurements
3.7 The horizontal Ussing chamber
3.7.1 Tissue preparation
3.7.2 Viability measurement
3.7.3 Drug transport
3.7.4 Histology
3.8 Statistical analysis
4. GELATION OF GELRITE GELS
4.1 Effect of ionic content
4.2 Temperature scans
5. MUCOADHESION
5.1 Mechanism and theory of bioadhesion
5.2 Methods of characterizing mucoadhesion
5.3 Mucin interactions with Carbopol 934 and Gelrite
6. INTERACTIONS BETWEEN POLYMER AND DRUG
6.1 Polymers used in the formulations
6.2 Effects on gel strength
6.3 Effects on drug release
7. INTERACTIONS BETWEEN POLYMER, DRUG AND NON-IONIC SURFACTANTS
7.1 Interactions between drug and surfactant
7.2 Effects on drug release
8. INTERACTIONS BETWEEN POLYMER, DRUG AND IONIC SURFACTANTS
8.1 Interaction between drug and surfactant
8.2 Effects on drug release
9. EVALUATION OF GELS IN THE USSING CHAMBER
9.1 The evaluated formulations
9.2 Transport over porcine nasal mucosa
10. CONCLUSIONS
ACKNOWLEDGEMENTS
REFERENCES
Author: Paulsson, Mattias
Source: Uppsala University Library
Download URL 2: Visit Now