Effect of Excipient Gelucire 44/14 on the Intestinal Transport of Diltiazem Hydrochloride in Male Wistar Rat
Excipients play a crucial role in drug disintegration, dissolution, absorption, distribution and transport. They are used in pharmaceutical formulations to modulate drug transport by multiple mechanisms including inhibition of intestinal P-gp. The main aim of this work was to investigate the effects of Gelucire 44/14 on the P-gp-mediated transport of Diltiazem a CYP3A4 substrate across the rat intestine.Diltiazem is mainly used in the treatment of hypertension and angina pectoris. It is mainly metabolized to desacetyl-Diltiazem and desacetyl-N-demethyl-Diltiazem in which CYP3A mediates this N-demethylation and desacetylation. Everted and non-everted sac methods were used to study the transport of Diltiazem across the rat intestine (duodenum, jejunum and ileum). The rats were treated with Gelucire 44/14 using different concentrations (0.5%, 1%).The rats were sacrificed by using anesthetic ether. The intestinal segments were isolated and used for the studies. The probe drug (Diltiazem) solution 10 mg/mL was placed in the isolated intestinal sac and placed in buffer (Dulbecco’s). Samples were collected periodically. The drug content was estimated using high performance liquid chromatography method (HPLC).Control experiments were also performed. The transport of Diltiazem increased in case of non everted studies and exsorptionvalues were found to decrease compared to control incase of everted studies. Results reveal that gelucire 44/14 at 1% concentration inhibit P-gp action effectively when compared to gelucire 44/14 at 0.5% concentration.