الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The objective of the present work was to formulate and characterize the timolol maleate (TMM)-loaded microsponges to improve ocular bioavailability and sustain drug delivery. Different hydrophobic polymers such as ethylcellulose (EC) and polycaprolactone (PCL) in different drug: polymer ratios were prepared by modified Quasi-emulsion solvent diffusion technique (water/oil/oil). Full factorial design was used to investigate the effect of different formulation parameters and optimize the best formulation depended on desirability value for further investigations. Then the optimized TMM-loaded microsponges was inserted into different in-situ gel formulations to increase its residence time and improving the bioavailability and therapeutic efficacy of TMM. These investigations together with the obtained results and the attained conclusions can be summarized as follows: TMM as a hydrophilic drug was successfully formulated by modified Quasi-emulsion solvent diffusion technique (water/oil/oil) with high production yield (%) and entrapment efficiency (%). All prepared TMM-loaded microsponges had a particle size range less than 10 μm, which will be a suitable for ocular application. All prepared TMM-loaded microsponges succeeded to sustain TMM release compared to TMM-aqueous solution with in-vitro kinetics data followed Higushi-diffusion model. Statistical analysis using ANOVA showed that the type of polymer (X1) and drug: polymer ratio (X2) had a significant effect on production yield (%), entrapment efficiency (%), particle size (nm), polydispersity index and TMM released (%) after 2 and 6 h from different prepared TMM-loaded microsponges (p < 0.0001). DSC, XRD and FTIR showed that the drug was imbedded into the prepared microsponges in its amorphous state, and the SEM revealed the pores structure of the spherical prepared microsponges. Ex-vivo permeation study showed that the optimized TMM-loaded formulation was succeeded to improve corneal permeation of hydrophilic drug (TMM) about 1.45-fold higher than the TMM-aqueous solution. In addition, ANOVA analysis showed that type of co-polymer (X1) and concentration of co-polymer (%) (X2) had a significant impact on sol-gel transition temperature (oC), muco-adhesion force (N), viscosity at 1 rpm and 10 rpm at different temperature, respectively and TMM released (%) after 2, 4 and 6 h, respectively from different prepared TMM-loaded microsponges in-situ gel formulations (p < 0.0001). Significant decrease in intra-ocular pressure was observed with the optimized in-situ gel and optimized microsponge formulation compared to its corresponding aqueous formulation with non-significant ocular irritation (p < 0.05).