Stability investigation of FCC-based tablets for oral suspension with caffeine and oxantel pamoate as model drugs.

Tablets for oral suspension (TOS) present a convenient alternative dosage form to conventional tablets. Dispersed in a glass of water or on a spoon, such tablets can be easily administered, which can become beneficial for pediatric or geriatric patients. The novel excipient functionalized calcium carbonate (FCC), consisting of calcium carbonate and calcium phosphate, has already shown to be suitable to produce orally disintegrating placebo tablets. In this study, the influence of formulation composition on disintegration time in water and artificial saliva was investigated using caffeine and oxantel pamoate as model drugs, reflecting BCS class 1 and BCS class 4, respectively. The optimized formulation for each model drug underwent a stress test. The results show that the drug content in DTs was not influenced by FCC under stressed conditions, however the disintegration and dissolution performance was affected by temperature and humidity. It can be concluded that it was possible to produce TOS characterized by rapid disintegration complemented by high physical stability of the tablets and chemical stability of the drug.

Simultaneous determination of praziquantel, pyrantel embonate, febantel and its active metabolites, oxfendazole and fenbendazole, in dog plasma by liquid chromatography/mass spectrometry.

A liquid chromatography-electrospray-mass spectrometry method (LC/MS) has been developed and validated for determination of praziquantel (PZQ), pyrantel (PYR), febantel (FBT), and the active metabolites fenbendazole (FEN) and oxfendazole (OXF), in dog plasma, using mebendazole as internal standard (IS). The method consists of solid-phase extractions on Strata-X polymeric cartridges. Chromatographic separation was carried out on a Phenomenex Gemini C6 -Phenyl column using binary gradient elution containing methanol and 50 mm ammonium-formate (pH 3). The method was linear (r(2) ≥ 0.990) over concentration ranges of 3-250 ng/mL for PYR andFEB, 5-250 ng/mL for OXF and FEN, and 24-1000 ng/mL for PZQ. The mean precisions were 1.3-10.6% (within-run) and 2.5-9.1% (between-run), and mean accuracies were 90.7-109.4% (within-run) and 91.6-108.2% (between-run). The relative standard deviations (RSD) were <9.1%. The mean recoveries of five targeted compounds from dog plasma ranged from 77 to 94%.The new LC/MS method described herein was fully validated and successfully applied to the bioequivalence studies of different anthelmintic formulations such as tablets containing PZQ, PYR embonate and FBT in dogs after oral administration.

Plasma pharmacokinetics, faecal excretion and efficacy of pyrantel pamoate paste and granule formulations following per os administration in donkeys naturally infected with intestinal strongylidae.

The plasma disposition, faecal excretion and efficacy of two formulations of pyrantel pamoate in donkeys were examined in a controlled trial. Three groups of seven donkeys received either no medication (control) or pyrantel paste or granule formulations at horse dosage of 20mg/kg B.W. (equals 6.94 mg/kg PYR base) of body weight. Heparinized blood and faecal samples were collected at various times between 1 and 144 h after treatment. The samples were analysed by high-performance liquid chromatography. The last detectable plasma concentration (tmax) of paste formulation was significantly earlier (36.00 h) compared with granule formulation (46.29 h). Although, there was no significant difference on terminal half lives (t1/2: 12.39 h vs. 14.86 h), tmax (14.86 h vs. 14.00) and MRT (24.80 h vs. 25.44 h) values; the Cmax (0.09 µg/ml) AUC (2.65 µgh/ml) values of paste formulation were significantly lower and smaller compared with those of granule formulation (0.21 µg/ml and 5.60 µgh/ml), respectively. The highest dry faecal concentrations were 710.46 µg/g and 537.21 µg/g and were determined at 48 h for both paste and granule formulation of PYR in donkeys, respectively. Pre-treatment EPG of 1104, 1061 and 1139 were observed for the control, PYR paste and PYR granule groups, respectively. Pre-treatment EPG were not significantly different (P>0.1) between groups. Post-treatment EPG for both PYR treatment groups were significantly different (P<0.001) from the control group until day 35. Following treatments the PYR formulations were efficient (>95% efficacy) until day 28. In all studied donkeys, coprocultures performed at day-3 revealed the presence of Cyathostomes, S. vulgaris. Faecal cultures performed on different days from C-group confirmed the presence of the same genera. Coprocultures from treated animals revealed the presence of few larvae of Cyathostomes.

Chemometric quality inspection control of pyrantel pamoate, febantel and praziquantel in veterinary tablets by mid infrared spectroscopy.

This paper describes the development and validation of a new multivariate calibration method based on diffuse reflectance mid infrared spectroscopy for direct and simultaneous determination of three veterinary pharmaceutical drugs, pyrantel pamoate, praziquantel and febantel, in commercial tablets. The best synergy interval partial least squares (siPLS) model was obtained by selecting three spectral regions, 3715-3150, 2865-2583, and 2298-1733 cm(-1), preprocessed by first derivative and Savitzky-Golay smoothing followed by mean centering. This model was built with five latent variables and provided root mean square errors of prediction (RMSEP) equal or lower than 0.69 mg per 100 mg of powder for the three analytes. The method was validated according the appropriate regulations through the estimate of figures of merit, such as trueness, precision, linearity, analytical sensitivity, bias and residual prediction deviation (RPD). Then, it was applied to three different veterinary pharmaceutical formulations found in the Brazilian market, in a situation of multi-product calibration, since the excipient composition of these commercial products, which was not known a priori, was modeled by an experimental design that scanned the likely content range of the possible constituents. The results were verified with high performance liquid chromatography with diode array detection (HPLC-DAD) and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and were in agreement with the predicted values at 95% confidence level. The developed method presented the advantages of being simple, rapid, solvent free, and about ten times faster than the HPLC ones.

Adsorption of pyrantel pamoate on mercury from aqueous solutions: studies by stripping voltammetry.

Adsorption and electrochemical reduction of pyrantel pamoate are studied in Britton Robinson buffer medium at hanging mercury drop electrode (HMDE) by Adsorptive Stripping Voltammetric technique. The peak current shows a linear dependence with the drug concentration over the range 250 ng mL(-1) to 64 microg mL(-1). Applicability to assay the drug in urine samples is illustrated in the concentration range 5-20 microg mL(-1).

The adsorption of cellulose ethers in aqueous suspensions of pyrantel pamoate: effects on zeta potential and stability.

This work examined the physico-chemical phenomena induced in aqueous suspensions of pyrantel pamoate by two varieties of hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) of different molecular weights, and the effects of these phenomena on the physical stability of the suspension. The mechanism of the interfacial adsorption of the polymer was investigated by constructing adsorption isotherms: for the two HPMC varieties, the isotherms were of type L and were fitted with the Langmuir model; of the NaCMCs, only the variety with higher molecular weight was adsorbed, its adsorption isotherm being of type S (sigmoidal). The resulting monolayer films were characterized viscosimetrically, determining their thickness and the number of polymer molecules adsorbed per unit area. The nonionic polymers formed thinner, more continuous monolayers than the NaCMC. Only the nonionic polymers significantly altered the zeta potential of the systems. In the range of conditions studied, all the polymers stabilized the initially flocculated systems, decreasing sedimentation volume and increasing the time necessary to redisperse them (the redispersability value). This stabilization occurred either by the steric mechanism (HPMCs and the high-molecular-weight NaCMC) or by depletion mechanisms (low-molecular-weight NaCMC). Owing to the complexity of these mechanisms, sedimentation volume was not found to be a useful index of the consistency of the sediments obtained from the suspensions.

[The technology for manufacturing antiparasitic preparations. 3. The development of a technology for producing the anthelmintic embovin (pyrantel embonate) in finely dispersed form and the evaluation of its anthelmintic properties]. / Tekhnologiia proizvodstva protivoparazitarnykh preparatov. 3. Razrabotka tekhnologii polucheniia antigel'mintika émbovina (pirantelia émbonata) v melkodispersnoi forme i otsenka ego protivogel'mintnykh svoistv.

Manufacturing process for anthelmintic embovin in a micronized form have been developed. Embovin in the micronized form exhibited the highest activity.