Belete, Anteneh(PhD)Mulualem,YohannesAbdela,Ebrahim2024-04-232024-04-232023https://etd.aau.edu.et/handle/123456789/2815The Citrus aurantifolia (Christm) Swingle species can be found in many parts of the world including the subtropical and tropical areas. It is a small shrubby tree, about 5 m length and has fruit has globule to oval nearly 3-6 cm diameter with a color range from light yellow to purple. Some studies revealed that citrus waste derived pectin- becoming promising way for based gastro- retentive (floating and bioadhesive) drug delivery systems formulation due to pectin’s economic, environmental and health related benefits. However, the floating and bioadhesive ability of the citrus aurantifolia peel pectin is not yet established. The bioavailability of furosemide is irregular through oral route and subjected to inter- or intra-subject variability. Hence, on the basis of its physico- chemical properties, it is a candidate drug for gastro-retentive formulations. Therefore, this study aimed to evaluate the potential of citrus Aurantifolia peel pectin as a polymer for preparing floating and bioadhesive matrix tablet using furosemide as a model drug. The citrus peel pectin was extracted from local citrus aurantifolia tree fruit peel using hot water extraction technique and characterized for several physicochemical properties such as the presence of carbohydrate, loss on drying, total ash, pH, water solubility index, swelling power, relative solubility, moisture sorption-desorption pattern, viscosity, powder flow properties and its compatibility with the model drug were investigated. Wet granulation method was employed to prepare the furosemide granules and the prepared granules were evaluated for particle size and distribution, bulk and tapped densities, compressibility index and Hausner ratio, angle of repose, flow rate, and the friability of the formulated tablets were evaluated. Other tablet quality parameters including friability, hardness, thickness, diameter, weight variation and content uniformity were assessed and in acceptable pharmacopeial standard. Based on the preliminary investigation, the pectin (10-40%) and effervescent agent (NaHCO3) (5-20%) concentrations were significantly affecting the response variables (p value < 0.05) such as floating duration (FD), bioadhesive strength (BS), swelling index (SI), drug release at 1 hr (DR1hr) and drug release rate (DRR)). Hence, further optimization study was conducted using central composite design (CCD) approach of design-expert 13 software. Both numerical and graphical optimization techniques were used for optimization. The Citrus aurantifolia tree fruit peel yielded 34.4% (w/w) purified pectin with light yellow color. Its pH and ash values were 4.6 and 2.29%, respectively. It showed solubility in hot water. The equivalent weight, methoxy content, anhydronic acid, and the degree v of esterification were 81.5, 13.84, 91.68, and 85.49, respectively which showed high methoxy pectin. The purified pectin powder had a Carr’s index of 36.6, Hausner ratio of 1.36 and angle of repose 32.78o which necessitates to conduct wet granulation technique. The compatibility study using FTIR and DSC analysis revealed that furosemide and citrus peel pectin were compatible. The drug release kinetic analysis of 13 formulations as per the CCD revealed best fits for Higuchi model with diffusion and erosion release mechanisms. The optimization results indicated that quadratic model was selected for swelling index and linear for the other responses. The adequacy of the model was evaluated using analysis of variance (ANOVA). Accordingly, the model provided an optimum formulation at 22.3% of pectin concentration and 5 % of effervescent agent. Under this condition, the software predicted floating duration (14.07 %), bioadhesive strength (28.57gm), swelling index (254.08%), drug release at 1hr (27.86%) and drug release rate (28.045 % / h-1/2). The optimization result predicted the optimized value of the independent variables to achieve desired responses was evaluated. The validity of this optimum formulation was confirmed experimentally. Based on the experimental studies, the validity of the model or software prediction was confirmed and the relative error are less than 5%. The flowability of the granule of optimized tablet was found excellent as the angle of repose was found to be <300 while the Carr’s and Hausner ratios were determined as < 10 and < 1.11 respectively. In conclusion, the results of this study enable to suggest that waste-derived citrus pectin can be used as an abundant alternative pharmaceutical excipient in the formulation and manufacture of floating and bioadhesive matrix tablets, leading to the formulation of an optimal floating and bioadhesive formulationen-USCitrus aurantifoliafloatingbioadhesivepectinoptimizationfurosemide.Thesis