No abstract

Diazoline, a 1,2,3,4-tetrahydrocarboline derivative, is capable of blocking Hwhistamine receptors and is used in medicine for the treatment of various allergic diseases [1].Specialists of the Pyatigorsk State Pharmaceutical Academy have developed a solid medicinal form ofdiazoline (tablets) based on the diazoline -13-cyclodextrin interaction.In order to study the pharmacokinetic characteristics of the new medicinal form, it was necessary to develop a method for monitoring the concentration of diazoline in the blood. The method based on chromatodensitometric analysis suggested in [2] is very cumbersome and labor-consuming. Moreover, in our opinion, the proposed technique does not ensure sufficiently complete isolation of diazoline from the biological liquid. For this reason, we have developed a new rapid technique for the quantitative determination of diazoline in the blood. We have selected HPLC as an analytical tool, since this method is now most widely used in drug analysis. EXPERIMENTAL PARTThe HPLC analyses were carried out on a Milikhrom-2 chromatograph (Russia) equipped with an UV detector and a KAKh 4-64-3 column filled with Separon C18.In order to select the optimum chromatographic conditions, we have preliminarily studied the retention time of diazoline and the coefficient of asymmetry of the corresponding peak as functions of the mobile phase composition.The chromatography was performed in the following regime: detection wavelength, 286 nm (maximum UV absorption of diazoline); scale factor, 1.6; eluent supply rate, 50 pl/min; chart velocity, 0.6 cm/min.As the mobile phase, we have studied aqueous ethyl alcohol solutions of various concentrations (60-90%). The samples for analysis were 2/al aliquots of a diazoline solution in DMSO with a concentration of 0.5 -5 mg/ml. I Pyatigorsk State Pharmaceutical Academy, Pyatigorsk, Russia.It was found that the HPLC chromatogram of diazoline has a single peak with the retention time and the asymmetry coefficient directly depending on the ethanol concentration in the mobile phase. The area under the peak is proportional to the diazoline solution concentration.The results of preliminary measurements showed that the optimum concentration of ethanol in the mobile phase is 80-90%, which corresponds to a retention time of 5.8 -6.5 min. Unfortunately, the peak of diazoline obtained for this eluent overlapped with peaks of the blood serum components and we had to reduce the ethanol concentration to 65-75%. However, this change led to asymmetry of the HPLC peak of diazoline. In order to improve the peak shape we have employed modifiers-glacial acetic acid (providing the regime of ionization suppression) and diethylamine (converting the drug into an ionized form). The amount of modifiers added to the eluent (0.5%) agrees with the commonly accepted level [2].Suppression of diazoline ionization in the presence of glacial acetic acid neither improved the peak shape nor 11 I1

Diprazin (promethazine) is a drug used in medical practice as an antihistamine. However, this compound is rather rapidly eliminated from the organism. In this connection, it would be important to develop a prolonged-release form of diprazin. In practice, prolongation of drug release is achieved by a number of methods such as binding to magnetic carriers, liposome filling, creation ofmacromolecular therapeutic systems, and covalent or noncovalent binding to hydrophilic polymer carriers [1]. The last method is simpler from the technological standpoint, and a wide assortment of medical polymers is available that provides the means for directed modification of the biopharmaceutical properties of drugs.The products of interaction between drugs and polymers are most frequently obtained by the method of joint mechanical dispersion, also called mechanical activation [2].The joint dispersion procedure usually involves an initial stage of breaking weak intermolecular bonds and intramolecular contacts in polymer macromolecules, which increases their reactivity. This is followed by the stage of product formation leading to the appearance of inclusion complexes or grafted complexes, depending on the particular polymer structure employed.We have developed a prolonged-release medication form of diprazin on the basis of poly(vinyl alcohol) (PVA). This polymer contains a large number of hydroxy groups readily forming hydrogen bonds with substances of different natures. Moreover, PVA belongs to the class of high-molecularweight compounds with limited swelling-a factor that can be used to reduce the rate of dissociation of the products of PVA -diprazin interaction [3].I Pyatigorsk State Pharmaceutical Academy, Pyatigorsk, Russia. EXPERIMENTAL CHEMICAL PARTWe have used diprazin (Akrikhin Joint-Stock Company) meeting the State Pharmacopeia (Ch. X) requirements, and a commercial PVA with an average molecular weight of 30,000. The interaction products were obtained by triturating diprazin with PVA in a porcelain mortar. The components were taken in drug-to-PVA ratios 1:0.05, 1:0.1 and 1:0.2, and triturated for 20, 40, or 60 rain. The products were studied upon dialysis through a cellophane membrane. An amount of the reaction products corresponding to a total diprazin content of 10 mg was dialyzed against 20 ml of water at 37~ The reference sample was obtained by parallel dialysis of 10 mg of the intact drug ground in the mortar. The contents of diprazin in the dialysates were determined by spectrophotometry at ;L = 250 nrn (~ = 887.25) [4].The results were compared upon calculating [5] the drug diffusion coefficient D by the formula 2 where Ct, mg/ ml, is the concentration of diprazin in a sample dialyzed during a time period oft, rain, Co, mg/mg is the maximum possible drug concentration in the dialysate, and S, cm 2 is the area of diffusion.The D values corresponding to a diprazin diffusion time of t = 90 min are presented in Table 1. As is seen from these data, a maximum reduction in the rate of diprazin diffusion (from 1.71 x 10-3 ...

No abstract

No abstract