Acta Pharm. 50 (2000) 315-328
Double layer (D.L.) suppositories specially designed for fast release performance were formulated with theophylline (TH). All the prepared suppositories passed the quality control tests. In these D.L. suppositories, the total drug dose is present in the outer layer and the core acts as its blank support. Among the different formulations tested, the one consisting of polyethylene glycol (PEG) blend in the outer layer and of the fatty base Suppocire (Supp.) NA10 in the core was selected for the best release properties. In all cases, the D.L. suppositories exhibited much higher release rates than either conventional or marketed suppositories. The apparatus used for release testing was the USP dissolution apparatus with a specially designed basket. Its suitability was confirmed by comparison with a membrane method. A selected D.L. formulation was stored at 30 °C, room temperature (6-30 °C), and 4 °C. The release rate for this selected formulation, as well as its drug content, during and at the end of the storage period of one year, showed no appreciable changes. However, slight changes were observed in disintegration times. It was also noticed that storage of a marketed suppository at 4 °C resulted in great enhancement of its release properties. The pharmacokinetics and bioavailability of TH from a conventional commercial fatty suppository and the selected fast release D.L. suppository were compared in 6 healthy male volunteers. Using a crossover design, saliva samples were collected at different time intervals over a period of 12 hours and assayed for TH by HPLC. Statistically significant differences existed between the D.L. and the commercial suppositories with respect to cmax, AUC0-12 and saliva TH-concentration at different time intervals. These findings were in favour of the D.L. suppository. A linear relationship was also established between the in vitro AUC0-t and AUC0-t obtained from the saliva concentration-time profiles.
Keywords: double layer theophylline suppositories, fast release, membrane method, storage, marketed product, bioavailability, human saliva