Investigation of the kinetic rate of dilept dissolution from pH-independent polymer matrices
Dilept, a tripeptide neurotensin analogue, a peptide drug, may be used as part of combination therapy for schizophrenia. The absorption of dilept occurs in the small bowel. Peptides are disintegrated by gastrointestinal tract (GIT) peptides. So it is important to choose a formulation that ensures the release of dilept in the small bowel. Polymer matrices provide the decelerated or delayed release of the drug, which can deliver dilept to that portion of GIT where its absorption will occur. The derivatives of cellulose [hydroxypropyl methylcellulose (hypromellose) - (Methocel® A15, E6, К4М, K-100-LV, K-100-M, and Walocel® 100000-PA, HM-15-PA)] and those of acrylic acid (Carbopol® 71G and Kollidon® SR) are employed as polymer matrices. The kinetic rate of dilept dissolution from pH-independent polymer matrices was investigated. Evaluation was made using the results of the dissolution test of polymer matrix tablets of dilept in accordance with the procedure described in the draft manufacturer's pharmacopoeia article (test time, 8 hours; device, a paddle stirrer; dissolution medium, isopropyl alcohol and water (1:8). The medium volume was 500 ml; the paddle rotational rate was 50 rpm. The time points for sampling were 1, 2, 3, 4, 5, 6, 7, and 8 hours, by compensating for the dissolution medium. The results were statistically processed using the Statistica 8.0 program. Investigation of the kinetic rate of dilept dissolution from pH-independent polymer matrices identified 2 types of release profiles (delayed and prolonged) that were also divided by the dissolution rate: zero- and first-order. According to the results of a dissolution test, Methocel® K4M Premium CR is more preferably used as a matrix to prepare long-acting tablets of dilept, which is associated with its release kinetics close to a zero-order one in vitro, and with the duration of release, which was close to that of GIT tablet passage (8 hours).