CIDCA   05380
CENTRO DE INVESTIGACION Y DESARROLLO EN CRIOTECNOLOGIA DE ALIMENTOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
THE INFLUENCE ON THE SPRAY DRYING PROCESS IN THE FORMULATION OF ALBENDAZOLE: β-CYCLODEXTRIN SYSTEMS
Autor/es:
AGUSTINA GARCÍA; DARIO LEONARDI; MARIA C. LAMAS
Lugar:
Rosario
Reunión:
Congreso; Ricifa 2012. 2º Reunión Internacional de Ciencias Farmacéuticas; 2012
Institución organizadora:
UNR - UNC
Resumen:
THE INFLUENCE ON THE SPRAY DRYING PROCESS IN THE FORMULATION OF ALBENDAZOLE: β-CYCLODEXTRIN SYSTEMS García A, Leonardi D, Lamas MC 1 Departamento de Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario. Suipacha 570, Rosario, CP: S2002LRK. Introduction Cyclodextrins (CDs) are natural or semisynthetic cyclic oligosaccharides with a central cavity having the ability to host a wide variety of hydrophobic compounds. The main pharmaceutical application of the design of CDs systems is to increase the apparent solubility of the included drugs.(1, 2) By far β-Cyclodextrin (β-CD) is the most widely used CD, consisting of seven glucopyranose units linked by α-(1,4) bonds. The mayor disadvantage is the exceptional low aqueous solubility and crystalline characteristics of β-CD (18,5 mg/mL at 25 ºC) limiting the improved solubility of poorly soluble compounds as a result of the solid combination. Many chemically modified β-CD have been synthesized, among which Methyl-β-Cyclodextrin (M-β-CD) and 2-Hydroxypropyl-β-Cyclodextrin (HP- β-CD) being excellent solubilizers due to the fact that their amorphous characteristics.(3) Albendazole (ABZ) is a broad spectrum anthelmintic drug that exhibits very low aqueous solubility, and as a consequence has an erratic bioavailability.(4, 5) The ability of cyclodextrins to solubilize drugs probably contributes to lower response variability. The aim of this work was to increase the apparent solubility and dissolution rate of ABZ formulation of inclusion complexes. The methodology selected for the preparation of ABZ:CDs complexes was spray drying methodology. Materials and methods The ABZ:CD systems at 1:1 and 1:2 molar ratios were prepared by two methods: Spray drying (SD) - ABZ (0.565 mmol) and CD (0.565 mmol or 1.131 mmol) were dissolved in 10.0 mL of acetic acid and 20.0 mL of water was added. Afterwards the solutions were sprayed (Buchi Mini dryer B-290). Physical mixture (PM) - ABZ and CD were mixed in a mortar for 10 min. ABZ, β-CD, M-β-CD, HP-β-CD and the systems prepared by both methods were analyzed by differential scanning calorimetry (DSC) and x-ray diffraction (XRD) studies. Solubility and dissolution profile studies of the systems were carried out. Results The systems prepared by SD showed an important increase in the dissolution rate in comparison with the physical mixtures and pure drug. Analyzing the dissolution profiles, the systems B, C, D and F (table 1) presented very similar behavior. Those systems released around 100 % of ABZ at 10 minutes, whereas in systems A and E, the percentage of drug release was 24% and 40%, respectively. These results could be attributed to an excess of CD in the systems at 1:2 molar ratio, which could form hydrogen bonds or another interaction with the drug. The XRD patterns of M-β-CD and HP-β-CD showed broad peaks indicating the amorphous nature of these compounds. On the other side, the XRD patterns of ABZ and β-CD exhibited a series of intense peaks, showing their crystalline character. The XRD patterns of ABZ:CD physical mixtures were practically constituted by the superposition of the single components, indicating no formation of a true inclusion complex. In contrast, the XRD patterns of the system prepared by SD exhibited broad peaks indicating the complex formation. These results also suggest that the systems prepared by SD were in amorphous state. Additional evidence of complex formation was obtained from DSC studies, where the absence of the endothermic peak of ABZ at 196.84 °C, proposing the formation of an inclusion complex. This event was observed in all DSC thermograms systems prepared by SD. Our results recommend that spray drying methodology could be an efficient technique to formulate complexes with β-CD presenting an amorphous state, increasing the dissolution rate and solubility of these complexes. Additionally, the results obtained from system B were similar to those obtained from complexes with readily soluble CDs (D and F). Conclusions The spray drying methodology was an efficient method to prepare ABZ-CDs inclusion complexes in amorphous state, highlighting the physicochemical advantages related to the improved drug release rate and the solubility. Acknowledgments The authors are grateful to National University of Rosario (UNR), and the National Council Research (CONICET). References 1) Del Valle EMM. Cyclodextrins and their uses: a review. Process Biochemistry. 2004;39(9):1033-46. 2) Giordano F, Novak C, Moyano JR. Thermal analysis of cyclodextrins and their inclusion compounds. Thermochimica Acta. 2001;380(2):123-51. 3) Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Advanced Drug Delivery Reviews. 2007;59(7):645-66. 4) Dayan AD. Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Tropica. 2003;86(2?3):141-59. 5) Cook GC. Use of benzimidazole chemotherapy in human helminthiases: Indications and efficacy. Parasitology Today. 1990;6(4):133-6. Table 1. Systems prepared by the two methods Components molar ratio Systems SD PM ABZ : β-CD 1 : 1 A G 1 : 2 B H ABZ : M-β-CD 1 : 1 C I 1 : 2 D J ABZ : HP-β-CD 1 : 1 E K 1 : 2 F M