Bollettino chimico farmaceutico最新文献

In a previous study, we developed a per-oral extended--release bioadhesive matrix tablet for verapamil HCl (VP). The system combined both strong bioadhesion and sustained release properties in vitro. The purpose of this study is to evaluate the in vivo performance of the prepared bioadhesive tablets (B). The conduction of a periodic X-ray imaging of the abdomen of beagle dogs, after administration of B containing 12% barium sulfate, was used to evaluate the intra-gastric performance. The VP concentrations in blood samples taken at specified times after oral administration of B to fasted beagle dogs were determined and compared with those obtained after administration of a commercial sustained release VP tablets (Manidon 120 R). The X-ray images showed that bioadhesive tablets remained almost at the same place in the stomach for at least 6 hours while it disappeared after 1 hour in case of the control tablets. No statistical difference was seen between the Cmax, tmax, AUC, t1/2, and MRT for B compared to Manidon. The Cmax was found to be 51.4 +/- 15.5 and 48.6 +/- 17.9 (ng/ml) for Manidon and B, respectively and the corresponding tmax were 7.0 +/- 1.9 and 6.0 +/- 0, respectively. The AUCO-. for Manidon and B were 949.84 +/- 245.11 and 722.92 +/- 144.42 ng.h/ml, respectively. So, the prepared B tablets can be considered bioequivalent to the commercial Manidon Retard product.

Air suspension coating is widely used in the pharmaceutical industry, as an attractive alternative to pan coating in that it can successfully coat small particles, pellets and tablets irrespective of size or shape with a wide variety of coating materials. The commercially available air suspension coating equipments require at least one kilogram of material for optimum efficiency of their working. Therefore, it is felt that there is a potential need for a small, compact air suspension coating instrument, which can work with gram quantities of material. The main objective of the present work is to design and evaluate a laboratory model top spray air suspension coating instrument. The performance of the instrument was evaluated for both, drug loading on to non-pareil pellets and coating of drug-loaded pellets. Terbutaline sulphate was selected as model drug, while Surelease (aqueous polymeric dispersion of ethyl cellulose) as representative coating material. The drug loading efficiency of the instrument was found to be around 82% with a pellet load of 10 g. The drug loading efficiency was found to be satisfactory and reproducible. Scanning electron micrographs of coated pellets indicated that coating was homogenous and uniform around the pellets. The maximum deviations observed in the in vitro drug release studies were +/- 2.7397% of the mean percent quantity of drug released, which is low enough for the coating to be considered uniform and reproducible. Reproducibility of the coating process was further confirmed by determining the 95% confidence interval for average difference in cumulative percentage drug release between two runs of each batch, which was found to be less than 5% set as the maximum allowable difference. The release data obtained were found to show best fit with first order kinetic model. A significant influence of coating thickness on the drug release rate was observed. From the results and observations of this work, it may be concluded that the mini-model air suspension coating instrument designed, may be a useful piece of equipment for preparing coated multiparticulate dosage forms in small quantities for sustained drug delivery, especially in research works.

In view of the widespread use of vitamin C several methods were developed for the determination of vitamin C in pharmaceutical preparation. Titrimetric and colorimetric methods commonly used to assay ascorbic acid. Unfortunately these methods have some failures regarding manipulative steps. Ascorbic acid oxidizes at DME and it can be a specific way with fewer steps in sample preparation in order to assay vitamin C. In this study a polarographic method was performed to determine ascorbic acid in several pharmaceutical dosage forms. The samples were prepared in oxalic acid solution and a standard addition method was performed during the experiments. The method has comparable precision compared with common method and it is even gave less error percent. Polarographic assay also is faster and easier to perform and could be used for routine determination.

The microbiological quality of different parts of vegetable drugs, commercialized in an open-air market, and intended for use as infusion preparations was compared. Total viable aerobic microorganisms, fungi, total and fecal coliforms and Enterobacteriaceae counts demonstrated lower sanitary quality in drugs composed of roots than those composed of leaves and caulis. E. coli was identified in some samples, but all of them were free from Salmonella sp.

The dynamics of total calcium concentration in blood of rat females with osteoporosis caused experimentally after applying it in the form of fumarate was determined. The fumarate was applied in just one dose by the means of stomach tube at the dose of teoporoz_ 4.28 mg of calcium/100 g of body mass. The total calcium concentration in blood was determined: 0; 1; 2; 3; 5 i 7 h after application. It was observed that one hour after application calcium concentration in control group increased by 19.3%, and in the group of animals after ovariectomy it decreased by 6.7% (P < 0.001). After 2 h calcium concentration in both groups returned to its initial state, and after 3 hours three next decrease in relation to initial time by 10% occurred in the control group and by 4% in the group after ovariectomy. Between 4 h and 7 h after administration calcium concentration in both groups of animals was even and it was maintaining at the constant level in the range 2.248-2.172 mM/l.

Liquid crystals are defined as the intermediary state between solid and liquid and also called of mesomorphous phase or crystalline phase, presenting characteristics of the mentioned physical states. For the simple emulsions that intermediary phase can act as forms of encapsulation of drugs providing its controlled liberation and besides, it can increase cutaneous hydration. These characteristics evidences the differentiation of the developed formulations and the use of the same ones in the release of new cosmetic vehicles. In that research we use vegetable oils (coffee, tomato), mineral oil, surfactants like phosphorics esthers (fractions A and B) and distilled water as aqueous phase. The stable formulations were submitted to stability physic-chemical preliminary tests (pH values determination, electric conductivity values, centrifugation and thermal stress) and later the compositions were submitted to accelerated stability tests (cold-hot cycle in the following temperature conditions--4 +/- 2 degrees C, 25 +/- 2 degrees C and 45 +/- 2 degrees C). Crystalline phase was identified by microscopy polarization. The recently prepared formulations and aged formulations (after 30 days) were appraised for rheology.

After the turn to market oriented economy a lot of drugs were authorized for sale in the East European countries. Because of the limited resources of these countries, mainly generic or brand generic products were licensed. The number of the patented drugs on the market could be used as measure of the market attractiveness to the R&D producers. The study shows the analysis of the innovativeness of the Bulgarian drug market comparing the registration and the patient activity of the producers. The number of the authorized products for five years period (1990-2000) and share of the patented products were investigated. During the observed period the number of newly authorized pharmaceuticals increased almost seven times from 800 (650 INN) to 6000 (2000 INN) dosage forms. The prevailing part of the newly registered drugs was found to be brand generics and possess only trade name protection. The share of drugs that are patented is less than five percent of all newly registered medicines, and among the fifty most commonly prescribed and sold medicines between 1996-2000, only 0.5 percent of drugs were patented. Obviously the Bulgarian pharmaceutical market is very competitive but not that attractive for most of the R&D producers. In general the registration of the patent protected products is increasing during the years and especially after harmonization of the related legislation with the EU requirements. The patent activity of the pharmaceutical companies regarding newly authorized drugs is influenced by the structure of morbidity and population. During the last two years the patent activity is increasing and is oriented mainly towards the protection of newly authorized drugs or pharmaceutical forms and obligatory registration of trademarks for the privatized Bulgarian pharmaceutical manufacturers.

The in vitro antimycobacterial activity of two ciprofloxacin analogues (2a and 2b) containing 2-phenyl-2-axoethyl and 2-(4-fluorophenyl)-2-axoethyl groups attached to N-4 position of piperazin ring, was evaluated against M. tuberculosis strains resistant to Isoniazid (MIC 2a and 2b = 3.13 micrograms/ml), Ethambutol (MIC 2a and 2b = 1.56 micrograms/ml), Rifampin (MIC 2a and 2b = 1.56 micrograms/ml), Kanamycin (MIC 2a and 2b = 1.56 micrograms/ml) and ciprofloxacin (MIC 2a and 2b > 25 micrograms/ml). Furthermore, the minimum bactericidal concentration (MBC) of 2a and 2b was determined against M. tuberculosis H37Rv (MBC2a = 6.25 and 2b = 25 micrograms/ml) and strains resistant to isoniazid (MBCs > 25 micrograms/ml) and rifampin (MBC2a = 3.13 and 2b = 6.25 micrograms/ml). Also, in this study the activity of 2a and 2b was determined against a strain of M. avium (%Inhibition 2a = 89 and 2b = 95%). Expanded primary screening was conducted for 2b (having MIC < 6.25 micrograms/ml) against five clinical isolates of M. avium using the MABA and BACTEC 460 systems (MIC = 2-4 micrograms/ml). The significant anti-Mycobacterium avium activity of 2b suggested further M. avium assays and so, 2b was then retested at lower concentrations against 30 strains of M. avium including five strains resistant to claritromycin (MIC = 2-16 micrograms/ml).

Helichrysum litoreum Guss, a Campania medicinal plant reported to have antibacterial properties, was evaluated for antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. The crude aqueous extract from leaves of Helichrysum litoreum at a concentration of 1.35 mg/ml (ww/v) showed significant antiviral activity on HSV-1 in human lung fibroblast as demonstrated by the absence of a cytopathic effect.

The effect of the composition of the coating (gelatine, sodium alginate, acetic acid) covering the biodegradable microcapsules upon their efficiency as well as upon albumin incorporation percentage value, were determined by the method of the 3 x 3 Latin squares. Selected physical and chemical properties of the microcapsules as well as the rate of albumin release from the microcapsules were investigated. Microcapsules suitable for parenteral administration were prepared using the method of a complex coacervation with the model substance: human albumin. None of the selected components of the coating was found to have any significant effect upon the efficiency of the microcapsules. However, it was established that the albumin incorporation effect was significantly influenced by gelatine concentration in the composition of the component. Based on the attained results, the composition of the biodegradable capsules was determined: 5% gelatine; 3% sodium alginate; and 25% acetic acid. Using the gelatin-sodium alginate system, microcapsules containing albumin with a prolonged release time, suitable for parenteral administration, were obtained.