[Show abstract][Hide abstract] ABSTRACT: The rate-limiting step to drug absorption is often dissolution from the dosage form, especially for poorly soluble compounds. Two possibilities for improving the dissolution of these drugs are to increase the available surface area and to improve their apparent solubilities under physiologically relevant conditions with surfactants as wetting agents. Albendazole (ABZ), one of the most effective broad-spectrum antihelminthic agents, has a very low aqueous solubility, which leads to an erratic availability. Solid dispersions (SD) with different amounts of carriers (P188 and PEG6000) were formulated to improve the ABZ dissolution rate. When the dissolution test is used to infer biopharmaceutical properties of the dosage form, it is essential that the method simulates the gastrointestinal conditions. The objective of this study was to examine the applicability of different dissolution media to the evaluation of ABZ and ABZ-SD dissolution rates. Dissolution profiles were performed by the official method (0.1 N HCl) and Simulated Gastric Fluid modified with a surfactant. Wetting was evaluated through the determination of surface tension and contact angle of the solutions. The dissolution rate of ABZ was clearly affected by the variables assessed in this study. These results have implications in the design of physiologically based dissolution media.
[Show abstract][Hide abstract] ABSTRACT: Cystic echinococcosis is a chronic, complex, and still neglected disease. Although albendazole has demonstrated efficacy, only about one-third of patients experience complete remission or cure and 30-50% of treated patients develop some evidence of a therapeutic response. Different strategies have been developed in order to improve the albendazole water solubility and dissolution rate. The aim of the current work was to investigate the chemoprophylactic and clinical efficacy of an albendazole:poloxamer 188 solid dispersion formulation on mice infected with Echinococcus granulosus metacestodes. Albendazole formulated as solid dispersion had greater chemoprophylactic and clinical efficacy than albendazole alone. The improved in therapeutic efficacy could be a consequence of the increase in the systemic availability of albendazole sulfoxide. The work reported here demonstrates that in vivo treatment with albendazole:poloxamer 188 impairs the development of the hydatid cysts. This new pharmacotechnically based strategy could be a suitable alternative for treating cystic echinococcosis in humans.
[Show abstract][Hide abstract] ABSTRACT: Microencapsulation of the Schinus molle Rev L. (Anacardiaceae) leaves essential oil (EO) has been employed to control the release of active ingredients, protecting them from the external environment, with the concurrent improvement of its insecticidal potential on Haematobia irritans. Four microcapsule formulations (EEO1 to EEO4) of S. molle EO were prepared by spray-drying, using a mini spray dryer and gum Arabic/maltodextrin (AG/MDX) as the carrier in different proportions, at a ratio of 4:1 (MDX/AG:EO). Encapsulation efficiency (EE: 96–100%), powder morphology and particle size distribution were analyzed as responses. An interesting correlation was found between EO free and microcapsules (EEO) in the preliminary and comparative studies of stability (at 45 °C) and in the insecticide activity on H. irritans. In fact, a very slow liberation profile of the microencapsulated EO (EEO4) was observed over a period of 366 h (71% of EO retention), as well as a slower time-dependent insecticide effect (32 and 73% of dead flies at 2 and 4 h of exposure time) compared to the free EO (96% of dead flies at 2 h).
[Show abstract][Hide abstract] ABSTRACT: Helminth infections are a major health problem mainly in developing countries, and the evidence of emerging resistance to all the major antihelminthics has been recognized in the field of animal husbandry. Albendazole (ABZ) is the most effective broad-spectrum antihelminthic agent. The biggest problem with this drug is its low aqueous solubility, which leads to an erratic availability and great intraindividual variation in the levels reached in different tissues. As with other poorly soluble compounds, the dissolution rate is likely to be contingent on the formulation and may lead to differences in performance among different products available in the market. In previous studies, drastic pharmacokinetic differences were observed among ABZ formulations (oral suspensions) in the Uruguayan market. These samples were evaluated in vitro in terms of ABZ content and dissolution profiles, as well as the effect of increasing agitation speeds on the dissolution rate. The in vitro dissolution rate of formulation A was seriously affected by the increase in agitation speed, and in the case of formulation B, it did not fulfill both essential quality requirements (drug content and dissolution profile). Further studies may be carried out to correlate the suspension quality with its therapeutic effectiveness.
[Show abstract][Hide abstract] ABSTRACT: The main objectives of this study were (a) to evaluate the
performance of the rapid disintegration tablets as a way to improve the solid dispersions and (b) to study the
pharmacokinetics of the albendazole modified formulation in dogs. Rapid disintegration of tablets seems to be a key factor for efficiency of solid dispersions with regard to improvement of the albendazole bioavailability. The
assays performed on dogs showed a marked increase in drug plasma exposure when albendazole was given in solid dispersions incorporated into rapid disintegration tablets compared with conventional solid dosage form.
[Show abstract][Hide abstract] ABSTRACT: Solid dispersions (SDs) containing the anthelmintic compound albendazole (ABZ) and either Pluronic 188 (P 188) or polyethylene glycol 6000 (PEG 6000) as hydrophilic carriers were formulated. Drug-polymers interactions in solid state were investigated using different techniques. Only a 4% of total ABZ was dissolved at 5 min post-incubation, reaching dissolution rates of 32.8% (PEG 6000) and 69.4% (P 188) in SDs. In this way, P 188 was substantially more efficient as ABZ dissolution promoter in comparison to PEG 6000, especially at the initial stages of the dissolution processes (<30 min). An increased systemic availability (p < 0.001) was obtained when ABZ was administered as ABZ-P 188 SDs, with a 50% enhancement in systemic exposure (AUC values) compared to treatment with an ABZ suspension. Consistently, the Cmax increased 130% (p < 0.001) following treatment with P 188 based SD ABZ formulation. For the ABZ-PEG 6000 SD formulation, the favorable effect on ABZ systemic availability did not reached statistical significance compared to the control group. The study reported here showed the utility of pharmacokinetic assays performed on mice as a model for preliminary drug formulation screening studies.
Pharmaceutical Development and Technology 06/2012; 18(2). DOI:10.3109/10837450.2012.693509 · 1.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Solid dispersions (SDx) containing Indomethacin (IND), a poorly water-soluble drug, and the disintegrant excipient sodium croscarmellose (SC) were prepared by a co-drying method and characterized by Infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). An FT-IR analysis performed on IND-SC solid dispersion and their physical mixtures indicated that IND does not interact with SC in the solid state. An analysis of the information produced by DSC, XRD, and SEM confirmed that the crystalline α-form of IND was homogeneously incorporated into SDx. IND release from SDx was significantly greater than that from its corresponding physical mixtures with the high homogeneous molecular dispersion and the crystalline modification of IND appearing to be the cause. This behavior may have a beneficial effect on the biopharmaceutical performance of this drug.
Journal of Excipients and Food Chemicals 01/2012; 3(4):121-128.
[Show abstract][Hide abstract] ABSTRACT: Dib, A., Palma, S., Suárez, G., Farías, C., Cabrera, P., Castro, S., Allemandi, D., Moreno, L., Lanusse, C., Sánchez Bruni, S. Albendazole sulphoxide kinetic disposition after treatment with different formulations in dogs. J. vet. Pharmacol. Therap.34, 136–141.
New therapeutic strategies based on the search of alternative formulations of albendazole (ABZ) and albendazole sulphoxide (ABZSO) are under current development to optimize posology and antiparasite efficacy in dogs. In an incomplete block design, nine dogs were randomly divided into three groups (n = 6). Treatments were carried out in two phases as follows. Phase I: Group I (treatment A), animals received ABZ at 25 mg/kg of conventional formulation. Group II (treatment B), dogs received 25 mg/kg of a modified poloxamer-ABZ formulation. Group III (treatment C), animals were treated with ABZSO in equimolar amount to ABZ doses. After 21 days of wash-out period the experiment was repeated (Phase II). Blood samples were collected over 24 h and subsequently analysed by high performance liquid chromatography. ABZSO and ABZSO2 were the analytes recovered in plasma. Significant higher (P < 0.001) ABZSO area under the concentration–time curve (+500%) and Cmax (+487%) values were obtained for the treatment C in comparison with treatments A and B. However, no statistical differences on pharmacokinetic parameters were found between formulations A and B. In conclusion, the enhanced plasma concentration profile obtained for the ABZSO formulation used in treatment C may contribute to optimize the anthelmintic control in dogs.
Journal of Veterinary Pharmacology and Therapeutics 04/2011; 34(2):136-41. DOI:10.1111/j.1365-2885.2010.01203.x · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Solids dispersions (SDs) have been proposed as an alternative to improve the dissolution rate of low solubility drugs. SDs containing albendazole (ABZ; 5, 10, 25, and 50% w/w) and Pluronic 188 (P 188) as hydrophilic carrier were formulated. The obtained SDs were assessed in comparison to physical mixtures (PMs). Drug-polymer interactions in solid state were investigated using Fourier-transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction analysis. No chemical interaction was found between ABZ and poloxamer. The dissolution profiles indicated that ABZ incorporated in SDs and PMs was rapidly released, reaching rapidly the steady state. Increased dissolution rates are usually observed at the highest polymer proportions. However, an opposite effect for SDs as well as for PMs was observed in the assays described here. The systems with the lowest P 188 percentages (SD4, SD3; PM4, PM3) tended to be more effective in increasing the ABZ dissolution rate. Such a result can be attributed to the fact that concentrated aqueous solutions of Poloxamer may form thermo-reversible gels. The physical-mechanical properties indicated that SDs possess improved flow and compacting properties compared to PMs. Thus, ABZ SDs would be more convenient for solid dosage form design and manufacture.