Gastroretentive delivery systems: hollow beads.
The objective of this study was to develop a floatable multiparticulate system with potential for intragastric sustained drug delivery. Cross-linked beads were made by using calcium and low methoxylated pectin (LMP), which is an anionic polysaccharide, and calcium, LMP, and sodium alginate. Beads were dried separately in an air convection type oven at 40 degrees C for 6 hours and in a freeze dryer to evaluate the changes in bead characteristics due to process variability. Riboflavin (B-2), tetracycline (TCN), and Methotrexate (MTX) were used as model drugs for encapsulation. Ionic and nonionic excipients were added to study their effects on the release profiles of the beads. The presence of noncross linking agents in low amounts (less than 2%) did not significantly interfere with release kinetics. For an amphoteric drug like TCN, which has pH dependent solubility, three different pHs (1.5, 5.0, and 8.0) of cross-linking media were used to evaluate the effects of pH on the drug entrapment capacity of the beads. As anticipated, highest entrapment was possible when cross-linking media pH coincided with least drug solubility. Evaluation of the drying process demonstrated that the freeze-dried beads remained buoyant over 12 hours in United States Pharmacopeia (USP) hydrochloride buffer at pH 1.5, whereas the air-dried beads remained submerged throughout the release study. Confocal laser microscopy revealed the presence of air-filled hollow spaces inside the freeze dried beads, which was responsible for the flotation property of the beads. However, the release kinetics from freeze dried beads was independent of hydrodynamic conditions. Calcium-pectinate-alginate beads released their contents at much faster rates than did calcium-pectinate beads (100% in 10 hours vs. 50% in 10 hours). It appears that the nature of cross-linking, drying method, drug solubility, and production approach are all important and provide the opportunity and potential for development of a gastroretentive drug delivery system.
Talukder
R
R
Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140, USA.
Fassihi
R
R
D000464:Alginates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005079:Excipients; D005772:Gastrointestinal Transit / Q000502:physiology*; D020723:Glucuronic Acid / Q000737:chemistry*; D006603:Hexuronic Acids / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008727:Methotrexate / Q000737:chemistry; D010368:Pectins / Q000737:chemistry*; D012256:Riboflavin / Q000737:chemistry
D000464:Alginates; D003692:Delayed-Action Preparations; D005079:Excipients; D006603:Hexuronic Acids; D010368:Pectins; D020723:Glucuronic Acid; D012256:Riboflavin; C003181:polygalacturonic acid; D008727:Methotrexate