IVIVC approach based on carbamazepine bioequivalence studies combination.

The aim of the present study was to explore the feasibility of obtaining an IVIVC by combination of data from two bioequivalence (BE) studies of carbamazepine (CBZ) in order to assess if the previously published dissolution media and conditions could be applicable to any other oral immediate release (IR) CBZ products with conventional excipients. Twenty-four healthy male subjects from two BE study received one IR dose of the test (test 1 or 2) or the reference formulation (Tegretol, 400 mg). Dissolution studies of the IR CBZ tablets were performed in two different laboratories. In order to develop IVIVC, individual or average data analysis were considered. A level C, level B and level A correlation have been successfully developed by combining data from different BE studies of CBZ immediate release drug products. A level A IVIVC was developed with all four datasets with a good R2 for all the combinations of in vivo and in vitro data. A dissolution medium containing 1% SLS has demonstrated its suitability as the universal biopredictive dissolution medium, even if different batches and in vivo/in vitro studies were combined.

Immunoproteomic analysis of Trichinella spiralis larval crude antigens recognized by sera from patients with trichinellosis after treatment with albendazole.

Antibody responses and antigen recognition were monitored during and after treatment with albendazole (ABZ) in nine patients selected from a trichinellosis outbreak that occurred in north-west Poland in 2007. Seven out of the nine patients yielded positive serum IgG response during treatment. One month after treatment, the IgG response decreased in most patients. Serum levels of ABZ and main metabolites greatly varied among patients without correlation with the IgG response. Two-dimensional electrophoresis and western blot with serum from each patient showed highly immunoreactive spots located between 3- 10 pI and 45-97 kDa in all patients. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF) and MALDI-TOF/time-of-flight mass spectrometry (TOF MS) analysis identified actine, enolase, p49 protein, Caenorhabditis elegans-targeted antigen, and serine protease as the most reactive proteins. A minor spot located at 6 pI and 26 kDa identified as annexin I failed recognition in most patients showing decline in IgG response and clinical improvement after treatment. This protein could constitute a sensitive marker for the effectiveness of ABZ against trichinellosis.

[Stability study of an aqueous formulation of captopril at 1 mg/ml]. / Estudio de estabilidad de soluciones acuosas de captopril en concentración de 1 mg/ml.

OBJECTIVE: The stability of captopril was studied in several extemporaneously prepared oral liquid formulations for pediatric use. Solutions were prepared at a concentration of 1 mg/ml from the pure chemical product. MATERIAL AND METHODS: Captopril 1 mg/ml oral liquid formulations were prepared from powder in three types of water (tap water, mineral water, distilled chemically pure water), in syrup and different chelating and antioxidants agents, and the pH was modified with sodium citrate. The liquids were stored at 4 and 25 degrees C in PVC plastic containers. Samples were removed at regular intervals of less than thirty days. Captopril and captopril disulfide concentrations were analyzed by high-performance liquid chromatography. Captopril in formulations in which the only vehicle was distilled chemically pure water were more stable than in formulations made either with tap water or with mineral water. RESULTS: The formulations containing edetate disodium, syrup, ascorbic acid, sodium ascorbate, sodium metabisulphite were less stable than those in which the only vehicle was distilled chemically pure water. The change of pH did not improve the formulation stability. The samples stored at 4 degrees C were much more stable than those stored at 25 degrees C, and the microbiological quality was much better. CONCLUSIONS: Captopril, at a concentration of 1 mg/ml, made with distilled chemically pure water stored in PVC plastic container and protected from light, was stable for 30 days at 4 degrees C.

Estudio de estabilidad de soluciones acuosas de captopril en concentración de 1 mg/ml / Stability study of an aqueous formulation of captopril at 1 mg/ml

Objective: The stability of captopril was studied in several extemporaneously prepared oral liquid formulations for pediatric use. Solutions were prepared at a concentration of 1 mg/ml from the pure chemical product. Material and methods: Captopril 1 mg/ml oral liquid formulations were prepared from powder in three types of water (tapwater, mineral water, distilled chemically pure water), in syrup and different chelating and antioxidants agents, and the pH was modified with sodium citrate. The liquids were stored at 4 and 25 °C in PVC plastic containers. Samples were removed at regular intervals of less than thirty days. Captopril and captopril disulfide concentrations were analyzed by high-performance liquid chromatography. Captopril in formulations in which the only vehicle was distilled chemically pure water were more stable than in formulations made either with tap water or with mineral water. Results: The formulations containing edetate disodium, syrup, ascorbic acid, sodium ascorbate, sodium metabisulphite were less stable than those in which the only vehicle was distilled chemically pure water. The change of pH did not improve the formulation stability. The samples stored at 4 °C were much more stable than those stored at 25 °C , and the microbiological quality was much better. Conclusions: Captopril, at a concentration of 1 mg/ml, made with distilled chemically pure water stored in PVC plasticc ontainer and protected from light, was stable for 30 days at 4 °C

Objective: The stability of captopril was studied in several extemporaneously prepared oral liquid formulations for pediatric use. Solutions were prepared at a concentration of 1 mg/ml from the pure chemical product. Material and methods: Captopril 1 mg/ml oral liquid formulations were prepared from powder in three types of water (tapwater, mineral water, distilled chemically pure water), in syrup and different chelating and antioxidants agents, and the pH was modified with sodium citrate. The liquids were stored at 4 and 25 °C in PVC plastic containers. Samples were removed at regular intervals of less than thirty days. Captopril and captopril disulfide concentrationswere analyzed by high-performance liquid chromatography. Captopril in formulations in which the only vehicle was distilled chemically pure water were more stable than in formulations made either with tap water or with mineral water. Results: The formulations containing edetate disodium, syrup, ascorbic acid, sodium ascorbate, sodium metabisulphite were less stable than those in which the only vehicle was distilled chemically pure water. The change of pH did not improve the formulation stability. The samples stored at 4 °C were much more stable than those stored at 25 °C , and the microbiological quality was much better.Conclusions: Captopril, at a concentration of 1 mg/ml,made with distilled chemically pure water stored in PVC plasticc ontainer and protected from light, was stable for 30 days at 4 °C

Albendazole versus ricobendazole (albendazole-sulphoxide) against enteral and parenteral stages of Trichinella spiralis in mice.

Comparison of the anthelmintic activity and pharmacokinetic profiles following albendazole (ABZ) and albendazole-sulphoxide (ricobendazole = RBZ) administration was made in a mouse model for helminthic infections. Swiss CD-1 mice were experimentally infected with Trichinella spiralis and treated with either ABZ or RBZ at 3 different stages of the parasite life-cycle: pre-adult (day 1 p.i.), migrating larvae (days 13, 14 and 15 p.i.) and encysted muscle larvae (days 34, 35 and 36 p.i.). Plasma concentrations of albendazole-sulphoxide (ABZSO) were measured in age matched non-infected mice by high performance liquid chromatography (HPLC), after administration of ABZ or RBZ dosed at 50 mg ABZ equivalent kg-1. ABZSO pharmacokinetic profiles following ABZ or RBZ administration were similar, although the Tmax (1.83 +/- 0.30 and 0.41 +/- 0.28, respectively) were significantly different (P < 0.01). Against pre-adult stages ABZ was significantly (P < 0.05) more effective than RBZ when administered at 10 mg kg-1 (96.5% and 78.0% reduction with respect to the control group). Migrating and encysted larvae were less sensitive to both compounds and dose rates had to be increased to 100 mg kg-1 to achieve significant efficacies. Against parenteral stages, ABZ was significantly more effective than RBZ when both were given at 100 mg kg-1 (64.0% and 44.2% reduction against migrating larvae and 94.7% and 65.5% reduction against encysted larvae, respectively). In conclusion, RBZ was not more effective than ABZ against enteral and parenteral stages of Trichinella spiralis.

Tableting characteristics of micro-aggregated egg albumin particles containing paracetamol.

The tableting characteristics of micro-aggregated egg albumin particles containing paracetamol were evaluated and compared with non-micro-encapsulated paracetamol and coagulated egg albumin particles. Mean yield pressure values of micro-aggregated egg albumin particles containing paracetamol and coagulated egg albumin particles were 30.5 and 49.3 MPa, respectively, which were lower than the mean yield pressure obtained for paracetamol (97.5 MPa). Paracetamol tablets obtained with micro-aggregated egg albumin particles did not show the capping characteristic of conventional paracetamol tablets. Crushing strength of paracetamol tablets obtained with egg micro-aggegated particles was similar to that obtained using paracetamol granulated with povidone and gelatin as binders at 3 and 6% (w/w) concentrations. Drug release from the paracetamol tablets depends on the choice of excipients. Crospovidone showed good protective characteristics for the tableting of micro-aggregated particles. Crushing strength of paracetamol tablets formed from egg albumin-coated particles could be increased using crospovidone or microcrystalline cellulose as fillers and was decreased by the use of magnesium stearate. Nevertheless, magnesium stearate was useful to decrease the ejection force.