Improved drug delivery to the lower intestinal tract with tablets compression-coated with enteric/nonenteric polymer powder blends.
The objective of this study was to develop pH-erosion-controlled compression-coated tablets for potential colonic drug delivery with improved gastric resistance and pulsatile release based on compression-coatings of powder blends of the enteric polymer Eudragit® L100-55 and the extended release polymer ethylcellulose. Tablet cores containing model drugs of varying solubilities (acetaminophen, carbamazepine and chlorpheniramine maleate) were compression-coated with different ratios of Eudragit® L100-55:ethylcellulose 10cP FP at different compression forces and tablet core:compression-coat ratios. The compression-coated tablets were characterized by drug release, media uptake, erosion behaviour and wettability. All drugs were released in a pulsatile fashion in higher pH-media after a lag time, which was controlled by the erosion properties of the Eudragit L:ethylcellulose compression-coating. The addition of ethylcellulose avoided premature drug release in lower pH-media and significantly increased the lag time in higher pH-media because of a reduction in wettability, media uptake and erosion of the compression-coatings. Importantly, ethylcellulose also reduced the pH-dependency of the erosion process between pH 5.5 and 7.4. The lag time could also be increased by increasing the compression force and decreasing the core:compression-coat ratio. In conclusion, tablets compression-coated with blends of Eudragit L and ethylcellulose resulted in excellent release properties for potential targeting to the lower intestinal tract with no release in lower pH-media and rapid release after a controllable lag time in higher pH-media.
Rujivipat
Soravoot
S
College of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Bodmeier
Roland
R
D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003106:Colon / Q000378:metabolism; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D010599:Pharmacokinetics; D011108:Polymers; D011109:Polymethacrylic Acids / Q000737:chemistry; D011208:Powders; D012995:Solubility; D013607:Tablets / Q000737:chemistry*
D005079:Excipients; D004364:Pharmaceutical Preparations; D011108:Polymers; D011109:Polymethacrylic Acids; D011208:Powders; D013607:Tablets; C038300:methylmethacrylate-methacrylic acid copolymer; C013517:ethyl cellulose; D002482:Cellulose