Peroral sustained-release film-coated pellets as a means to overcome physicochemical and biological drug-related problems. I. In vitro development and evaluation.
In vitro preformulation testing has shown that the solubility and dissolution rate of the model drug compound ucb 11056 are highly pH dependent. Considering this, different sustained-release (SR) oral dosage forms of ucb 11056 were developed aiming to obtain the most constant and complete release of the drug during transit in the gastrointestinal (GI) tract. Classical approaches based on the use of SR formulations such as hydrophilic matrix tablets or pellets coated with one film-forming polymer (Eudragit NE30D or L30D-55) did not fulfill all expectations on the basis of their in vitro evaluation, i.e., the drug release and pattern remained highly dependent on the pH of the dissolution medium. Therefore, taking advantage of the flexibility of release adjustment obtainable from coating of pellets with different kinds of pH-sensitive film layers, a quite satisfactory pH independence of the release characteristics was obtained using formulation blends of neutral and anionic acrylic polymers. For the selected SR pellets batch 15 coated with NE30D/L30D-55 (7:3), the tridimensional topographic representation of the drug release versus time and pH showed that, notwithstanding the pH-dependent aqueous solubility of the drug, the release profiles were relatively homogeneous for any pH value ranging between 1 and 7.
Amighi
K
K
Laboratoire de Pharmacie Galénique et de Biopharmacie, Université Libre de Bruxelles, Belgium.
Timmermans
J
J
Puigdevall
J
J
Baltes
E
E
Moës
A J
AJ
D000180:Acrylic Resins; D000284:Administration, Oral; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003692:Delayed-Action Preparations; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D008956:Models, Chemical; D009025:Morpholines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids; D012995:Solubility; D014227:Triazines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D009025:Morpholines; D011109:Polymethacrylic Acids; D014227:Triazines; C084361:2-(4-morpholino-6-propyl-1,3,5-triazin-2-yl)aminoethanol; C038300:methylmethacrylate-methacrylic acid copolymer