Average Disintegration Time Research Articles

Enteric Coatings V : pH Dependence and Stability

Evidence is presented that the terms “stable in acid solutions” and “soluble in alkaline solutions” should not be applied to enteric coatings. The enteric substances studied dissolve in buffers of pH less than 7 and tablets coated with these substances disintegrate in fluids having a pH less than 7. It was demonstrated that the critical pH range in which tablets coated with styrene-maleic acid copolymer show a progressive decrease in disintegration time corresponds to a narrow pH range on either side of the pK1 of the copolymer. It is in this region that the greatest change in per cent ionization of the copolymer occurs. Relating these in vitro data with in vivo data, formerly reported, will require adjustment of current concepts of enteric coatings. It was shown that the disintegration times of tablets coated with styrenemaleic acid copolymer, dibutyl phthalate, and talc in artificial intestinal fluid, pH 6.9, changed very little after storage of the coated tablets for prolonged periods at 4°, room temperature, 40°, and 47°. Tablets coated with the other enteric compositions exhibited either decreased resistance to simulated gastric fluid or markedly increased disintegration times in artificial intestinal fluids after prolonged storage. It was demonstrated that the average disintegration time observed after storage of enteric coated tablets for one month at 47° yields an excellent prediction of the average disintegration time of the tablets after storage for two years at room temperature.

Correlation of in vivo with in vitro Disintegration Times of Enteric Coated Tablets

The stomach retention and intestinal disintegration times of six lots of enteric coated tablets were determined roentgenographically in the dog. The resistance of the coatings to simulated gastric fluid U. S. P. and disintegration times of the whole enteric coated tablets and of the subcoated tablets in artificial intestinal fluid, pH 6.9, were determined. Graphs and equations are presented which express the observed relationship between the average intestinal disintegration time in the dog and the average disintegration time of the whole enteric coated tablet or of the enteric coating only in artificial intestinal fluid. All data were analyzed statistically.