Optimization of the pharmacological efficiency of methamphetamine for local application

Abstract

Organic compounds of an acidic character are widely used as drug preparations [1]. However, the use of these drugs, in particular for the treatment of local damages in tissues, is considerably limited by their generally low solubility in water. A trivial using organic acids in the form of alkali metal salts helps create an optimum drug concentration only in the first approximation. This is related to a high pH level in 9 the zone of action of these salts and a rapid decrease of their initial concentration as a result of elimination with fluids fi:om the organism. Eventually, the intensity and duration of the therapeutic action of the organic drugs having an acidic character markedly drops.In this paper we suggest an original way to solve the problem of optimization of the pharmacological effect of methamphetamine (MH) by creating its composition with an alkaline form of an ion-exchanger sorbent (Na-zeolite). This choice of objects for the investigation is important in connection with the use of MH and its sodium salt (MNa) as antiinflammatory drugs [2] and in the context of reported biological effects ofzeolites [3]. EXPERIMENTAL PARTExperiments were conducted with pharmacopeial-grade methamphetamine, a synthetic zeolite (Si/AI= 1.95; total exchange capacity with respect to Na +, 4.7mg-equiv./g; pore volume, 0.36 cm 3 / g [4]), and doubly distilled water.The model kinetic experiments were performed with MH ~-NaX systems with the molar ratios MH :Na= I : 10; 1:5; 1:0.5; and 1:0.25; the amount of MH (2 x 10-4 mole) and the volume of the aqueous phase (100 ml) were the same in all experiments.The UV spectra were measured on a Specord UV-VIS spectrophotometer using quartz cells (l = 1 cm). The values of pH were measured with a pH-121 instrument equipped with a glass electrode. The appearance of an ionic acid form was determined using the UV spectra of an aqueous phase of the MH-NaX -H20 system, given preliminary mixing of the solid components and a fixed time of their contact with the solvent (not less than eight measurements in the interval from 10 to 60 min).Pharmacological tests were performed on a group of both male and female white Wistar rats weighing 180 -220 g fed with a standard diet.The acute toxicity of the MH + NaX composition was determined upon peroral administration as described in [5]; the toxic effect was followed during a 5-day period after the drug's introduction.The antiimqammatory effect was evaluated by the degree of edema inhibition in rats with induced burning of hind paws (60~ for 5 see) [6]. The substances were applied onto the burned surface 2 h after the thermal irritation, when the edema had reached 210 -215 % of the initial paw volume.The analgesic action was assessed by a decrease in the pain sensitivity threshold of inflammed extremities [7].The composition MH + NaX and individual components (M/I, MNa, and NaX) were applied onto the damaged surface with a sterile gauze tampon wet with distilled water, and MNa was applied as a paste with a white clay base.The drugs were applied at a mol...

Some aspects of the technology for liposomal medicinal preparations

“…According to the published data [1,2,13,25,38,39] the optimum storage temperatures for liposomal preparations range from 5_+3~ lbr a liposomal anti-influenza (type A) vaccine to -10~ for the new antihypoxant Lipin.…”

“…The process of liposome formation includes the following sequence of necessary stages: (i) preparation of lipid films from high-purity lipids oxidized to a minimum extent; (ii) emulsification of the lipid in a buffer solution or a solvent containing substances to be included in liposomes; (iii) formation of liposomes by conventional methods; (iv) separation of residual substances not encapsulated in liposomes; (v) clarification and sterilization of the liposomal preparation; (vi) pouring preparations into storage containers; (vii) freezing, lyophilization, and hermetization of preparations in an inert gas atmosphere; (viii) storage under preset conditions with periodic quality control [1,2,13]. It must be noted that According to our experience, the standardization and quality control of medicinal liposomal preparations must inelude determination of the following parameters: dimensions of liposomes; sterility, pyrogenicity, and toxicity of preparations; ratio (quantitative) of the lipid and drug components forming a given liposomal preparation; pH of the liposomal system; presence of stabilizing agents.…”

“…The liposomal fonns of some cytostatics and hepatoprotectors were obtained by high-pressure homogenization [1,2,13]. It was reported that liposomes containing antibiotics of the anthracycline series (doxorubicin) changed in size from 160 + 30 to 220 _+ 40 nm upon lyophilization.…”