Increasing the solubility of naproxen by including it into amorphous gamma cyclodextrin


Increasing the solubility of naproxen by including it into amorphous gamma cyclodextrin


Hristo Veselinski, Tsveta Sarafska, Stiliyana Pereva, Tony Spassov, Svetla Bogdanova, Maya Spassova
Faculty of Chemistry and Pharmacy, Sofia University “Saint Kliment Ohridski”, Bulgaria


Cyclodextrines, are cyclomalto-oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by α-1,4-glycosidic bonds. These structures are in the shape of a truncated cone, the outer part of which has hydrophilic nature, while a hydrophobic cavity is formed inside. These structural features of cyclodextrins allow the inclusion of a large number of drug substances in their hydrophobic cavities, forming “host-guest” complexes. Gamma-cyclodextrin (γ-CD) is a cyclic oligosaccharide formed by bacterial digestion of starch and is used as a solubilizing agent and stabilizer in various pharmaceutical and food products. Like other cyclodextrins, γ-CD can form water-soluble inclusion-complexes with otherwise very poorly soluble compounds. Compared to natural α-CD and β-CD, γ-CD has the largest hydrophobic cavity, the highest water solubility and the most favorable toxicological profile. The goal of the present study is the possibility of increasing the solubility of naproxen (characterized by very low water solubility causing undesirable gastric reactions) by forming a complex with amorphous-γ-CD. For this purpose amorphous-γ-cyclodextrin is obtained and is structurally and thermally characterized. “Host-guest” type of inclusion complexes were obtained between crystalline and amorphous-gamma-cyclodextrin and naproxen, and the degree of inclusion of the complexes obtained by various techniques was determined by differential scanning calorimetry. The structure and microstructure of the complexes was determined by scanning electron microscopy. To prove the complex formation in the final products, X-ray-diffraction analysis was used.
Key words: solubility, cyclodextrin, naproxen, DSC, SEM