Polyoxyethylene-poly(methacrylic acid-co-methyl methacrylate) compounds for site-specific peroral delivery.
pH-sensitive interpolymer interactions between high molecular weight polyoxyethylene (POE) and poly(methacrylic acid-co-methyl methacrylate) (Eudragit (EUD) L100 or S100) are evidenced and exploited to prepare, from either POE-EUD coevaporates or POE+EUD physical mixtures, both in the 1:1 wt. ratio, compressed matrix tablets, potentially able to deliver the model drug, prednisolone, to sites in the GI tract characterized by specific pHs, such as the jejunum or the ileum. With these devices, drug release is inhibited at pHs lower than the threshold of EUD ionization, whereas at pHs exceeding such a threshold, the matrix undergoes a gradual erosion, which controls the release. A post-compression exposure of tablets to the vapors of appropriate solvents realizes the necessary compaction of matrices, in fact, a high compression force (3 ton) is insufficient, per se, to prevent matrix disintegration in the dissolution medium, whereas such a disintegration is prevented by the treatment with solvent vapors, even with a low compression force (0.3 ton). With the POE+EUD physical mixtures, the exposure to solvent vapors promotes the formation of a layer of POE-EUD complex at the interfaces of the POE and EUD particles in matrix, which inhibits release at pHs lower than that designed for delivery. Both POE and EUD concur to determine the properties of the POE-EUD complex relevant to drug release, indeed, EUD ionization, which elicits matrix erosion and drug release, is favored by the hydrophilic POE. In fact, matrices based on plain EUD exhibit a comparatively low release rate, more suited to an extended delivery to the colon than to a specific delivery to the ileum. Details of the release mechanism are discussed.
Carelli
V
V
Department of Bioorganic Chemistry and Biopharmaceutics, University of Pisa, Via Bonanno 33, 56126, Pisa, Italy.
Di Colo
G
G
Nannipieri
E
E
Poli
B
B
Serafini
M F
MF
D000284:Administration, Oral; D019245:Compressive Strength; D016503:Drug Delivery Systems / Q000379:methods*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011239:Prednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics; D013607:Tablets
D005938:Glucocorticoids; D011108:Polymers; D011109:Polymethacrylic Acids; D013607:Tablets; D011092:Polyethylene Glycols; D011239:Prednisolone