Studies on dissolution testing of the nifedipine gastrointestinal therapeutic system. I. Description of a two-phase in vitro dissolution test

• Published in: Journal of controlled release Vol. 48; no. 1; pp. 1 - 8
• Main Authors: Grundy, John S, Anderson, Keith E, Rogers, James A, Foster, Robert T
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 22.09.1997; Elsevier
• Subjects: Biological and medical sciences; Dissolution testing; Gastrointestinal therapeutic system; General pharmacology; In vitro release profile; Medical sciences; Nifedipine; Octanol; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Sink conditions; Gastrointestinal therapeutic system; Dissolution testing; In vitro release profile; Octanol; Sink conditions; Nifedipine; Pharmaceutical technology; Calcium antagonist; Intestinal juice; Oral administration; Gastrointestinal; Dissolution; In vitro; Biphasic system; Dosage form; Active ingredient; Tablet; Dihydropyridine derivatives; Release; Physicochemical properties
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(97)00064-3

The nifedipine gastrointestinal therapeutic system (GITS) incorporates a push–pull osmotic pump to release–in zero-order fashion–a finely-divided 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 characterize the in vitro nifedipine suspension release rate from the nifedipine GITS: however, these methods fail to measure the in vitro dissolution rate of the suspended particles–a potentially significant shortcoming considering that nifedipine is poorly water-soluble (≤10 μg ml − 1). Therefore, an in vitro two-phase dissolution system was developed. This system measured the rate of nifedipine `transfer' 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 from the tablet, dissolution in the aqueous phase and partitioning in the organic phase. For the 30 mg and 60 mg nifedipine GITS formulations tested the two-phase method indicated that about 90% of the drug was `transferred' within 30 h. This is in contrast to the results from single-phase dissolution methods showing that about 90% of drug is `released' within 24 h. Results obtained from the two-phase dissolution method appear to be in better agreement with published in vivo studies of the nifedipine GITS with regard to the rate and duration of nifedipine absorption from the GI tract. This emphasizes the importance of differentiating between drug release and drug dissolution for this type of formulation: but, the two-phase dissolution method may also be useful for other pharmaceutical formulations and poorly water-soluble drugs.