Experimental study of the bioaccessibility of phenotropyl tablets in vivo and in vitro

Abstract

Phenotropyl (N-carbamoylmethyl-4-phenyl-2-pyrrolidone) is a phenyl derivative of pyracetam patented as a drug possessing significant nootropic activity [1]. This study was aimed at experimental evaluation of the bioaccessibility of phenotropyl in vitro and in vivo. EXPERIMENTAL PARTPhenotropyl release in vitro from tablets. One of the factors determining the bioaccessibility of tablets is the rate and completeness of drug release from this ready-to-use medicinal form. In order to study this factor, we have preliminarily measured the UV spectra of phenotropyl in aqueous solutions and in 0.1 N HCl solutions in water -ethanol (7 : 3) mixture. The measurements were performed on a Specord M40 spectrophotometer (Germany) using 10-mm-thick cells, with reference to the pure solvent. It was found that the UV spectrum of phenotropyl in both solvents has a pronounced maximum at l = 258 nm.At a phenotropyl concentration of 0.2 mg/ml, the optical density of the aqueous solution was D = 0.19 and that of the acid aqueous ethanol solution was D = 0.26. In the drug dissolution test, one 0.1 g phenotropyl tablet was dissolved in 500 ml of water or 0.1 N HCl solution in water -ethanol (7 : 3) mixture. The tests were performed in a "rotary basket" type device operating at 100 rpm. The optical density of the drug solution at 258 nm was measured 15 min after the onset of dissolution. The solution concentration was within 0.17 -0.18 for the aqueous solution and 0.22 -0.28 for the acid aqueous ethanol solution, which was indicative of a virtually complete release of phenotropyl from tablets within 15 min in both cases.Based on the results of preliminary tests, we selected the following standard procedure for the investigation of phenotropyl release from 0.1 g tablets. The test was performed in accordance with the General Pharmacopoeial Article OFC 42-0003-00: dissolution media, 0.1 N HCl solution in water and 0.1 N HCl solution in water -ethanol (7 : 3) mixture; basket rotation speed, 100 rpm. The tests were performed on a Dissolutest device (Prolabo, France) equipped with an EE 599 Cecil automated scanning spectrophotometer (UK) linked to an PC Apple IIC computer for data processing and an Epson LX-800 printer for recording. The optical densities of samples were measured at 258 nm in 10-mm-thick cells. The measurements were performed every minute for the aqueous HCl solution and every three minutes for the aqueous ethanol solution, in both cases over a period of 20 min. The latent time was t 0 = 1.2 min. Figure 1 shows the experimental dynamics of phenotropyl release from 0.1 g tablets in the two solvents. The drug release was described in terms of the exponential model, according to which the percentage drug release ( f, % of dose introduced) varies with time aswhere k s is the rate constant of drug release [min -1 ]; t 0 is the latent period [min]; and t is the current time of dissolution [min]. Figure 2 presents the experimental dynamics of phenotropyl release from 0.1 g tablets plotted in semilogarithmic coordinates (i.e., in terms...