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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/13491
Title: DISSOLUTION ENHANCEMENT OF ALBENDAZOLE USING SOLID DISPERSION TECHNIQUE
???metadata.dc.contributor.*???: Professor Tsige Gebre-Mariam
Dr. Fitsum Feleke
Beza Teshome
Keywords: Albendazole; HPMC; Kneading; PEG; Physical mixture; Polysorbate 80; PVP; Solid dispersion; Solvent evaporation
Issue Date: Jul-2016
Publisher: AAU
Abstract: Albendazole (ABZ) is a benzimidazol (BZD) derivative with broad spectrum of activity against human and animal helminth parasites. However, its poor water solubility gives rise to formulation problems and reduced bioavailability. These problems can be reduced by increasing the dissolution rate of the drug using different approaches such as solid dispersions (SDs). This study was designed to formulate ABZ loaded SDs with improved dissolution profiles. For this purpose, binary and ternary SDs were prepared by kneading and solvent evaporation methods using the hydrophilic carriers such as polyethylene glycol 4000 (PEG), polyvinyl pyrrolidone K-30 (PVP) and hydroxypropyl methylcellulose 5 cps (HPMC) and the surfactant polysorbate 80. To prepare binary SDs, the carriers were used in three drug: carrier proportions (1:0.5, 1:1, 1:2), where as in case of ternary SDs, polysorbate 80 was added at 0.1 proportion of the pure drug for all proportions of the carriers used. Physical mixtures (PMs) containing the above mentioned carriers were similarly prepared for comparison purpose. Fourier Transformer Infrared Spectroscopy (FTIR) studies of the samples stored for 2 months revealed interaction through hysdrogen bonding between the drug and the carriers. Differential Scanning Calorimetry (DSC) of the PMs and SDs indicated decreased crystallinity of the drug. Dissolution profiles of ABZ were remarkably improved from the binary and ternary SDs as well as from ternary PMs than the pure drug (4.50% within 60 min). The rate and extent of dissolution was significantly higher in the ternary systems than the binary systems (p < 0.5). Solvent evaporation method demonstrated the highest dissolution profile. The ternary SD of ABZ with PEG and polysorbate 80 at a ratio of 1:2:0.1 prepared with solvent evaporation technique showed the highest dissolution profile with 100% of the drug released within 60 min. The SDs with PEG showed higher dissolution profiles than with PVP in both the SDs prepared by kneading and solvent evaporation techniques. From the SDs prepared by kneading method, the highest drug release was observed with the carrier HPMC (88.8% of the drug being released with 60 min) followed by PEG (81.4%). In all the formulations the release of ABZ was shown to increase with increasing carrier proportions. XIII The prepared SDs were characterized for flow properties and compressibility. Tablets of selected SDs were prepared by direct compression method and evaluated for their quality attributes. The results revealed that the major factors that affect the SDs and tablet characteristics are carrier to drug ratio, the amount of microcrystalline cellulose (MCC) and compression force. Thus, 3 factors, two level (2 3) full factorial experimental design was selected to investigate the effects of the selected factors on the various responses such as flow property, compressibility and drug release in 10 min and 60 min. Accordingly, the various models describing the relationship of the selected variables were obtained using Design-Expert 9.0.6 software and the optimum area was determined. The optimal points for the responses were found to be 55.09% for amount of ABZ released within 10 min, 81.27% for amount of ABZ released within 30 min, 29.48° for angle of repose, 94.60 N for hardness and 0.62% for friability when the factors are set at compression force of 14.03 KN, carrier to drug ratio of 1.98 and concentration of MCC of 23.57%. The validity of obtained optimal point was confirmed experimentally. Evaluation of the optimized formulation showed successful formulation of ABZ SD tablets. The release profiles of the optimized tablet formulation were superior to marketed tablets. Thus, it can be concluded that the dissolution of ABZ is significantly enhanced by SD technique.
Description: A Thesis Submitted to School of Graduate Studies of Addis Ababa University in Partial Fulfillment of the Requirements for the Degree of Master of Science in Pharmaceutics
URI: http://hdl.handle.net/123456789/13491
Appears in Collections:Pharmacology and Clinical Pharmacy

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