Formulation and in-vivo evaluation of verapamil HCI suppositories

Verapamil-HCl (V-HCl) was formulated in the form of rectal suppositories in an attempt to obviate the first-pass effect. Two formulations (F1 and F2), each containing 60 mg of V-HCl, were selected for the in-vivo evaluation in 6 healthy male subjects, using two (V-HCl) tablets (Isoptin®, 80 mg each) as a reference. F1 contains a water-soluble base (PEG-1500 :PEG-6000 :H 2 O, 65 :28 :7). F2 contains a mixture of Witepsols® as a fatty base (H15 :E75 :H 2 O, 72 :24 :4). A third formula (F2-C) was prepared by incorporating 5% camphor in F2, which is expected to increase blood circulation in the rectal compartment, and was given to one subject. The plasma concentration of the drug was determined by an HPLC method using fluorimetric detector. The prepared suppositories exhibited superior rate and extent of absorption. Statistical analysis of the results using paired t-test proved that rectal administration of V-HCl has significantly improved the pharmacokinetic parameters of the drug regarding onset of action, extent of absorption and duration of therapeutic activity. The observced T max values for F1, F2, F2-C and the reference were 1.08, 0.33, 1.25 h and 2.1 h, respectively. The calculated percent bioavailability, based on AUC 0-8 h, relative to the reference tablets were 237, 134 and 227% for F1, F2 and F2-C, respectively. The corresponding values from AUC 0-α were 195, 281 and 960% for F1, F2 and F2-C, respectively.