pH-sensitive film coatings: towards a better understanding and facilitated optimization.
The major aims of this study were: (i) to prepare and characterize polymeric film coatings with pH-dependent properties for oral administration; and (ii) to better understand the underlying mass transport mechanisms upon exposure to simulated gastric and intestinal fluids. Propylene glycol alginate (containing free carboxylic groups) was chosen as a pH-sensitive film former, which was blended with different amounts of ethylcellulose (being water-insoluble throughout the gastro-intestinal tract). The water uptake kinetics of thin free films in 0.1M HCl and phosphate buffer pH 7.4 were monitored gravimetrically and quantitatively described using an appropriate analytical solution of Fick's law of diffusion. Interestingly, the addition of only a low percentage (2.5-10%) of propylene glycol alginate to ethylcellulose significantly increased both, the rate and extent of the films' water uptake, irrespective of the pH of the release medium. Importantly, diffusion was found to be the pre-dominant mass transport mechanism for all system compositions and types of release media. The apparent water diffusivity in the polymeric films could quantitatively be determined as a function of the polymer blend ratio. It significantly increased with increasing pH of the release medium, due to the presence of the free carboxylic groups in propylene glycol alginate. Also the dry mass loss of the polymer networks was much more pronounced at high compared to low pH. The differences in both water uptake as well as dry mass loss resulted in a clear pH-dependence of the drug release kinetics from coated pellets. Importantly, desired pH-sensitive release rates can easily be adjusted by varying the propylene glycol alginate content.
Siepmann
F
F
College of Pharmacy, University of Lille, 3 Rue du Professeur Laguesse, Lille, France.
Wahle
C
C
Leclercq
B
B
Carlin
B
B
Siepmann
J
J
D000464:Alginates / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D005750:Gastric Juice / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000378:metabolism; D007700:Kinetics; D013806:Theophylline / Q000737:chemistry; D014867:Water / Q000378:metabolism
D000464:Alginates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D014867:Water; C038550:propylene glycol alginate ester; C013517:ethyl cellulose; D002482:Cellulose; D013806:Theophylline