STUDIES ON DISSOLUTION TESTING OF THE NIFEDIPINE GASTROINTESTINAL THERAPEUTIC SYSTEM .1. DESCRIPTION OF A 2-PHASE IN-VITRO DISSOLUTION TEST

The nifedipine gastrointestinal therapeutic system (GITS) incorporates a push-pull osmotic pump to release-in zero-order fashion-a finely-di vided suspension of nifedipine, which must then undergo dissolution in the GI tract before the drug can be absorbed. Classical, differential (ALZA) and flow-through type dissolution methods adequately character ize the in vitro nifedipine suspension release rate from the nifedipin e GITS: however, these methods fail to measure the in vitro dissolutio n rate of the suspended particles-a potentially significant shortcomin g considering that nifedipine is poorly water-soluble (less than or eq ual to 10 mu g ml(-1)). Therefore, an in vitro two-phase dissolution s ystem was developed. This system measured the rate of nifedipine 'tran sfer' from an aqueous phase (simulated intestinal fluid, USP, without pancreatin containing a nifedipine GITS tablet) into an organic phase (n-octanol), a process dependent on release of the drug suspension fro m the tablet, dissolution in the aqueous phase and partitioning in the organic phase. For the 30 mg and 60 mg nifedipine GITS formulations t ested the two-phase method indicated that about 90% of the drug was 't ransferred' within 30 h. This is in contrast to the results from singl e-phase dissolution methods showing that about 90% of drug is 'release d' within 24 h. Results obtained from the two-phase dissolution method appear to be in better agreement with published in vivo studies of th e nifedipine GITS with regard to the rate and duration of nifedipine a bsorption from the GI tract. This emphasizes the importance of differe ntiating between drug release and drug dissolution for this type of fo rmulation: but, the two-phase dissolution method may also be useful fo r other pharmaceutical formulations and poorly water-soluble drugs. (C ) 1997 Elsevier Science Ireland Ltd.