Purpose: To evaluate a previously proposed multiple-unit pulsatile delivery formulation, based on a swellable hydroxypropyl methylcellulose (HPMC) inner layer and a poly(ethylacrylate, methylmethacrylate) (Eudragit®NE)/sodium starch glycolate (Explotab®V17) (5:1) outer film, as a carrier for colonic release of insulin and the absorption enhancer sodium glycocholate (NaGly). Methods: Minitablets containing insulin and NaGly (1:10) were coated in a fluid bed with aqueous formulations of HPMC and Eudragit®NE/Explotab®V17, respectively. The latter coat was intended to slow down water penetration into the underlying HPMC one thus improving its effectiveness in delaying drug release. To overcome gastric emptying variability and enable time-based colon delivery, an external enteric film was applied employing a hydro-alcoholic hydroxypropyl methylcellulose acetate succinate (Aqoat®AS) solution. In vitro release (2h HCl 0.1M, 4h pH 6.8) and, preliminarily, physical stability (4°C, 3 months) were evaluated. Results: Gastroresistant formulations showed no drug liberation in the acidic fluid, whereas a concomitant pulsatile release of insulin and NaGly was observed in simulated intestinal conditions after reprdoucible lag phases. Insulin t10% (i.e. the time for 10% release) was unchanged with respect to a non-gastroresistant reference system suggesting that no major influence would be exerted by the enteric coating on the performance of the functional layers. Moreover, t10% values remained practically unchanged (p>0.05) for both the protein and the absorption enhancer after three-month storage at 4°C. Conclusion: A previous multiple-unit oral pulsatile delivery system was adapted for colonic delivery of insulin. Enteric formulations showed the desired release behaviour, which was not altered following storage under refrigerated conditions.
|Titolo:||Preparation and in vitro evaluation of a multiple-unit formulation for oral colonic delivery of insulin|
|Settore Scientifico Disciplinare:||Settore CHIM/09 - Farmaceutico Tecnologico Applicativo|
|Data di pubblicazione:||set-2013|
|Tipologia:||Book Part (author)|
|Appare nelle tipologie:||03 - Contributo in volume|