|dc.contributor.advisor||Professor Tsige Gebre-Mariam||en_US|
|dc.contributor.advisor||Dr. Fitsum Feleke||en_US|
|dc.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||en_US|
|dc.description.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.
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.||en_US|
|dc.subject||Albendazole; HPMC; Kneading; PEG; Physical mixture; Polysorbate 80; PVP; Solid dispersion; Solvent evaporation||en_US|
|dc.title||DISSOLUTION ENHANCEMENT OF ALBENDAZOLE USING SOLID DISPERSION TECHNIQUE||en_US|
|Appears in Collections:||Pharmacology and Clinical Pharmacy|