[In vitro equivalence evaluation of betahistine generic medicinal products as a tool potentially determining the efficacy of pharmacotherapy]. / Otsenka ékvivalentnosti in vitro vosproizvedennykh preparatov betagistina kak instrumenta, potentsial'no opredeliaiushchego éffektivnost' farmakoterapii.

AIM: To compare release parameters of various betahistine drugs in vitro using a comparative dissolution kinetics test. MATERIAL AND METHODS: Objects of research are solid dosage forms (tablets) containing betahistine in a dose of 24 mg permitted for medical use in the Russian Federation. A method of comparative dissolution kinetics test was carried out as follows. The study was performed on a paddle stirrer at a speed of 50 rpm in three different pH dissolution media (pH 1.2, 4.5, 6.8), simulating the main sections of the digestive tract in which the active ingredient was decomposed, released and absorbed. This was performed in a quality controlled environment using a citrate buffer solution with pH 6.8. The time points for sampling the medium were 10 min, 15 min, 20 min and 30 min. RESULTS: The results of betahistine release were significant (RSD<10%) for all time points, except the first time point (RSD<20%). Regardless of pH, there was a complete release (≥85% over 15 minutes, <10%) of betahistine from betaserc, 24 mg, tablets (manufactured by Mylan Laboratories SAS). The dissolution profiles of betahistine in other investigational drugs did not show complete drug release (parameter <85% in 15 minutes, <10%) in different pH media. Therefore, dissolution profiles of the studied drugs were not comparable to the reference profile. CONCLUSION: Starting from 10 minutes, the reference drug of betahistine (betaserc, 24 mg) has a consistently higher release at different pH levels (representing the various stages of gastric digestion), vs. other studied generic analogues showing significantly lower levels of betahistine release. None of the studied drugs were found to be equivalent in vitro.

[Oncolytic Properties of a Mumps Virus Vaccine Strain in Human Melanoma Cell Lines].

The oncolytic potential of the attenuated mumps virus (MV) vaccine strain Leningrad-3 (L-3) was evaluated in a panel of four human metastatic melanoma cell lines. The lines were shown to be susceptible and permissive to MV infection. Efficient MV replication led to death of melanoma cells, but the effect differed among the cell lines. Possible mechanisms mediating the selectivity of MV L-3 towards the cell lines were explored. Replicative and oncolytic activity of MV was found to depend on the expression pattern of type I interferon genes. None of the melanoma cell lines showed induction of expression of the total spectrum of genes required to inhibit virus replication. Based on the results, MV L-3 was assumed to be a promising oncolytic agent for human melanoma cells.

[Biodistribution of Rifabutin Polymeric Transport Form].

BACKGROUND: One way to increase drug efficacy is to provide a drug delivery transport system to the target organ. A widely used method is to incorporate the drug in a biodegradable polymer composition with forming nanosized drug's transport forms. Objective: Our aim was to investigate the tissue biodistribution of antibiotic rifabutin transport system based on lactic and glycolic acids copolymer, and to compare it with the pure substance of rifabutin. METHODS: These substances were administered to two groups of rats intragastrically in the doses of 10 mg/kg. After a certain period of time, the animals were sacrificed by cervical dislocation. Samples preparation for analysis was carried out of the liquid-liquid extraction. Active substance's concentrations were measured by high performance liquid chromatography method. RESULTS: The study included 8-week-aged Wistar rats of both sexes weighing 0.22 ± 0.02 kg. Animals were divided into 2 groups. The study group received polymer form of antibiotic, and the comparison group received substance of rifabutin. In intervals of 10 min, 30 min, 1 h, 2 h, 4 h, 7h, 15 h, 24 h after drug administration liver, lung, spleen, kidney, intestines, stomach, heart and brain were resected respectively. Organs were measured by their weight. The drug was not detected in the brain. Rifabutin was determined in other examined tissues within 10 minutes and the maximum drug concentration in organs was fixed in 1.5-3.5 hours after administration. The rifabutin concentrations defined in the lungs were significantly higher in polymerform (p < 0.05). The polymer form's distribution coefficient was higher in the liver and lungs (15.83 and 10.14 µg/g respectively) in comparison with the substance one. The minimum amount of the active ingredient was observed in the heart (0.02 µg/g). CONCLUSION: It is shown that the inclusion of the drug in a polymeric form substantially alters its localization in organs and tissues. Extensive biodistribution nanorifabutin in lung tissue, liver and spleen is established.

Interchangeability evaluation of multisource Ibuprofen drug products using biowaiver procedure.

The WHO biowaiver procedure for BCS Class II weak acids was evaluated by running two multisource IR ibuprofen drug products (Ibuprofen, 200 mg tablets, Tatchempharmpreparaty, Russia and Ibuprofen, 200 mg tablets, Biosintez, Russia) with current Marketing Authorizations (i.e. in vivo bioequivalent) through that procedure. Risks associated with excipients interaction and therapeutic index were considered to be not critical. In vitro dissolution kinetic studies were carried out according WHO Guidance (WHO Technical Report Series, No. 937, Annexes 7 and 8) using USP Apparatus II (paddle method) at 75 rpm. Dissolution profiles of test and reference ibuprofen tablets were considered equivalent in pH 4.5 using factors f(1) (13) and f(2) (72) and not equivalent in pH 6.8 (factor f(1) was 26 and f(2) was 24). Drug release of ibuprofen at pH 1.2 was negligible due to its weak acid properties. Therefore, two in vivo bioequivalent tablets were declared bioinequivalent by this procedure, indicating that procedure seems to be over-discriminatory.