Development and characterization of advanced pharmaceutical systems with sulfanilamide

[A. D. Tačić]

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Biobibliografija: listovi 138-147; Bibliografija: listovi 112-131.

Chemistry and chemical technology

Advanced pharmaceutical systems for drug delivery can provide better bioavailability, safer and more effective application of active substances, by increasing their solubility and stability while improving pharmacological activity and reducing side effects. Sulfanilamide is a broad-spectrum, synthetic antimicrobial drug whose application in therapy is limited by its poor water solubility and photosensitivity. The aim of the present doctoral dissertation was preparation and characterization of various pharmaceutical systems (inclusion complexes, hydrogels and liposomes) with sulfanilamide, in order to increase solubility and photostability while maintaining antimicrobial activity of sulfanilamide and enabling its modified delivery. For that purpose, sulfanilamide was synthesized using the conventional method, purified and characterized by using FTIR, 1H-NMR, XRD, DSC i SEM methods. Inclusion complexes of sulfanilamide with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin were prepared using the coprecipitation method and characterized by using FTIR, 1H-NMR, XRD, DSC and SEM methods, which proved the incorporation of sulfanilamide into the cyclodextrin cavities. Phase-solubility and photostability studies have shown that solubility and stability of sulfanilamide increase after incorporation into cyclodextrin molecules, especially in the case of 2-hydroxypropyl-β-cyclodextrin. The formation of inclusion complexes with cyclodextrins also increases the potency of the sulfanilamide antimicrobial action due to the increase of its solubility in water. Homopolymeric p(NIPAM) hydrogels were synthesized using free radical polymerization process, with varying crosslinker content, and characterized using FTIR, XRD and SEM methods. The residual reactant content was determined by using HPLC method and the swelling degree of the synthesized hydrogels was determined gravimetrically. Sulfanilamide was incorporated into the synthesized and characterized hydrogels, which is proved by using FTIR, XRD and SEM methods. The effect of temperature, pH and the crosslinker content on the rate of sulfanilamide release from the hydrogels was examined. It has been shown that p(NIPAM) hydrogels can be suitable carriers for sulfanilamide. MLV liposomes with sulfanilamide were prepared by the thin film method, and unilamellar liposomes of adequate size and satisfactory stability, with a very narrow particle size distribution, were prepared by extrusion. The release of sulfanilamide from the liposomes was examined using dialysis sac method, relative to the buffer solution, indicating that sulfanilamide incorporation into liposomes halves its rate of release. The release of sulfanilamide from liposomes is best described by the Korsmeyer-Peppas model, with Fickian diffusion as predominant release mechanism. The photostability of sulfanilamide increases after incorporation into liposomes, while MLV liposomes have the greatest protective effect. The photodegradation products of sulfanilamide: sulfanilic acid, aniline and benzidine, were identified by using UHPLC-DAD-HESI-MS/MS method. The photodegradation of sulfanilamide is a free radical reaction influenced by •OH radicals and follows first order kinetics.

Sulfanilamid, inkluzioni kompleksi, hidrogelovi, liposomi, fotostabilnost, degradacioni proizvodi

Sulfanilamide, inclusion complexes, hydrogels, liposomes, photostability, degradation products

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