Active Pharmaceutical Ingredients with poor solubility have presented significant difficulties in drug product design and development including slow and ineffective absorption leading to inadequate and variable bioavailability. Therefore it has become increasingly desirable to overcome the low aqueous solubility of drug candidates and develop more novel and innovative formulation approaches to increase the dissolution rate of the poorly soluble drugs. This work focuses on the formulation of novel amorphous ibuprofen-polymer nanoconjugates based on the polymer-drug complexation in order to improve its physical and dissolution characteristics without the use of toxic organic solvents. Plain and ibuprofen-loaded binary and ternary nanoconjugates were prepared using four modified co-precipitation techniques including melt solubilization; alkaline solubilization; surfactant solubilization and hydrotropic complexation techniques. A remarkably high loading capacity was achieved ranging from 89.05 to 99.49% across the four techniques and polymer-polymer ratio of 50:50 was found to be most efficient. All the four techniques reduced the size of ibuprofen (2.87 μm) significantly in the presence of 2.0 x10-3 mM of Diethylaminoethyl Dextran (DEAE-Dextran) in the order melt solubilization (203.25 nm) > alkaline solubilization (185.68 nm) > surfactant (Tween 80) solubilization (122.17 nm) > hydrotropic complexation (77.92 nm). 5.0 x 10-4 mM of chitosan also reduced the size of ibuprofen from 2872.12 to 10.70 nm (268-fold reduction). The FTIR spectroscopic analysis revealed electrostatic, hydrophobic and hydrogen bonding interaction between solubilized ibuprofen and the cationic polymers (DEAE-Dextran and chitosan) to form a new product (an amide). Polymer-polymer complexation also occurred between DEAE-Dextran and gellan as well as chitosan and gellan to a different extent depending on the mixing ratios. 1H and 13C NMR analysis confirmed the conjugation between ibuprofen and each of the cationic polymers as well as the formation of a new amide product. DSC thermal analysis showed that the nanoconjugates exhibited new broad and diffuse peaks confirming that they did exist in amorphous state as multiple complexes. The TGA thermograms of the binary nanoconjugates exhibited one step degradation profile compared with the physical mixture which exhibited two steps. However the ternary nanoconjugates exhibited two steps degradation profile confirming the formation of multiple complexes. Marked enhancement of drug release was achieved by the four techniques compared with the ibuprofen control. All the DG (DEAE-Dextran - Gellan) complexes exhibited a higher release profile than ibuprofen control. Fickian and non-Fickian anomalous mechanisms were deduced for the drug release of ibuprofen from the binary conjugates. The ternary nanoconjugates exhibited non-Fickian (anomalous) diffusion, Fickian diffusion and Super Case II transport release mechanisms. The ternary nanoconjugate hydrogels exhibited complete release (100%) within 48 h. The lowest concentration of DEAE-Dextran, Gellan - Ibuprofen - DEAE-Dextran (GIbDD) 2:0.125, increased the release of ibuprofen by 13.4% however higher concentrations of DEAE-Dextran decreased the release profile steadily. It was concluded that DEAE-Dextran has potentials in the formulation of modified (extended) release of ibuprofen. The most prominent mechanism of release of ibuprofen from the nanoconjugate hydrogel was Super Case II transport. SEM and AFM micrographs of the drug loaded composite pharmaceutical films exhibited concentric spheres with two and three layers for the binary and ternary films respectively. This supports the evidence of internalization of ibuprofen by the polyelectrolyte complex. The FTIR and DSC results confirmed electrostatic and hydrophobic interactions between ibuprofen and DEAE-Dextran as well as between gellan and DEAE-Dextran. Thermal analysis revealed that plain bilayer films were thermally more stable than composite films. The addition of ibuprofen significantly increased (p < 0.05, n = 4) the swelling ratio of the films compared with films without the drug. The drug loaded bilayer films exhibited Fickian diffusion mechanism while the dominating mechanism for composite films was anomalous (Non-Fickian) transport. From the foregoing, it was evident that ibuprofen-polymer nanoconjugate present a novel tool for the delivery of ibuprofen with potential application for transdermal delivery.

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This work deals with the current topic of carrier systems. Since the biggest problem is the passage of hydrophobic drugs through the bloodstream, or through universal body barriers (eg blood-brain), it is necessary to chemically modify these carriers in order to be able to administer hydrophobic substances effectively. Based on a literature search, several systems are designed and subsequently studied, in which there is a presumption of possible use for carrier systems and at the same time they have biosurfactants incorporated in them due to their ability to solubilize hydrophobic molecules. The theoretical part of this work will describe the individual biosurfactants, the process of their production, their physicochemical properties, and the possibility of their use in carrier systems. At the same time, the individual carrier systems, the procedure of their preparation, the possibilities of their use are described, and their advantages and disadvantages are also compared. In the practical part, the screening of both individual substances and their mutual interactions, as well as methods used to study the emerging structures is then performed. The study of molecular interactions is primarily performed using the technique of dynamic light scattering. The next part describes the optimization of hydrogel formation with incorporated biosurfactants in their structure and then the formed gels are subjected to rheological and solubilization tests. The study of the internal structure of these gels is performed using a scanning electron microscope.