ABSTRACT
Aim of this work was the evaluation of an oral system (Chronotopic) designed to achieve time and/or site-specific release. The system consists in a drug-containing core, coated by a hydrophilic swellable polymer which is responsible for a lag phase in the onset of release. In addition, through the application of an outer gastroresistant film, the variability in gastric emptying time can be overcome and a colon-specific release can be sought relying on the relative reproducibility of small intestinal transit time. For this study, cores containing antipyrine as the model drug were prepared by tableting and both the retarding and enteric coatings were applied in fluid bed. The release tests were carried out in a USP 24 paddle apparatus. The in vivo testing, performed on healthy volunteers, envisaged the HPLC determination of antipyrine salivary concentration and a gamma-scintigraphic investigation. The in vitro release curves presented a lag phase preceding drug release and the in vivo pharmacokinetic data showed a lag time prior to the detection of model drug in saliva. Both in vitro and in vivo lag times correlate well with the applied amount of the hydrophilic retarding polymer. The gamma-scintigraphic study pointed out that the break-up of the units occurred in the colon. The obtained results showed the capability of the system in delaying drug release for a programmable period of time and the possibility of exploiting such delay to attain colon-targeted delivery according to a time-dependent approach.
Subject(s)
Drug Delivery Systems , Lactose/analogs & derivatives , Methylcellulose/analogs & derivatives , Administration, Oral , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Antipyrine/administration & dosage , Antipyrine/chemistry , Antipyrine/pharmacokinetics , Colon/metabolism , Drug Carriers , Humans , Male , Middle Aged , Oxazines , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/pharmacokinetics , Technetium Tc 99m Pentetate/administration & dosage , Technetium Tc 99m Pentetate/pharmacokineticsABSTRACT
This paper reports the in vivo and in vitro evaluation of an oral system for time and/or site specific drug delivery prepared according to Chronotopic technology. The proposed device consists of a drug containing core coated by a hydrophilic polymeric layer, which determines the delay in release onset. By applying an outer gastroresistant film, and by properly modulating the delay duration, a colon-specific release can be achieved. The obtained results show that the proposed delivery system is capable of releasing drug after a programmed time (time-specific release) and of targeting the colon (site-specific release) when an external gastroresistant film is applied on units coated with an appropriate amount of a hydrophilic retarding polymer.
