Abstract
Oral administration of indomethacin has been limited by its poor water solubility. Cyclodextrins have been recognized as potential candidates to overcome the poor solubility of indomethacin through the formation of inclusion complexes. The aim of our study was to compare the dissolution profiles of pure indomethacin and its mixtures with α- and γ-cyclodextrins The inclusion complexes of indomethacin with α- and γ-cyclodextrins were prepared by direct mixing in dissolution vessel. Fixed volumes of the dissolution medium were withdrawn at 0,5; 1 and 4 hours. Dissolution tests were performed on the USP Apparatus 2, rotating speed 100 rpm at 37±0.5 ° C, 500 ml, distilled water and 0,1 M HCl solution). Quantification of dissolved indomethacin was performed by UV/VIS spectrophotometric method at the absorption maximum around 320 nm. The results were expressed as relative dissolution rate (ratio between indomethacin dissolved from its physical mixtures with α- and γ-cyclodextrins and that dissolved the pure drug). Relative dissolution rates of indomethacin in combination with α- and γ-cyclodextrins at the end of testing were in the range of 91,66 to 337,14 % (for α- cyclodextrin) and in the range of 128,57 to 301,92 % (for γ-cyclodextrin). The complexation of indomethacin with α- and γ-cyclodextrins resulted in the enhancement of dissolution rate.
Highlights
Cyclodextrins are cyclic oligosaccharides consisting of six α, seven-β, eight-γ, nine-δ, ten ε-cyclodextrins or more glycopyranose units linked by α-(, ) α-D-glucopyranose units (, ) They are produced as a result of intra-molecular glycolisation, which occurs during starch degradation mediated by cyclodextrin glycanotransferase (CGTase) enzyme ( )
E hydroxyl functions are orientated to the cone exterior with the primary hydroxyl groups of the sugar residues at the narrow edge of the cone and the secondary hydroxyl groups at the wider edge. e central cavity of the CD molecule is lined with skeletal carbons and ethereal oxygens of the glucose residue, which gives it a relatively lipophilic character (, )
Solubility of indomethacin can be improved by formation of inclusion complexes with α-CD or γ-CD, regardless of molar ratio of the prepared physical mixture
Summary
Cyclodextrins ( known as cycoamyloses, cyclomaltoses and Schardinger dextrins) are cyclic oligosaccharides consisting of six α-, seven-β, eight-γ, nine-δ, ten ε-cyclodextrins or more glycopyranose units linked by α-( , ) α-D-glucopyranose units ( , ) They are produced as a result of intra-molecular glycolisation, which occurs during starch degradation mediated by cyclodextrin glycanotransferase (CGTase) enzyme ( ). E central cavity of the CD molecule is lined with skeletal carbons and ethereal oxygens of the glucose residue, which gives it a relatively lipophilic character ( , , , , , ). The hydroxy groups form hydrogen bonds with the surrounding water molecules resulting in a hydration shell around the dissolved CD molecule ( , , , ). Cyclodextrins (CD) interact with poorly-water soluble compounds to increase their apparent solubility. The increased apparent solubility can enable solution-based dosage forms such as parenteral i.v. formulations and oral liquids. Increasing the apparent solubility of a drug can, through the Noyes–Whitney equation, increase drug dissolution rate and for compounds whose bioavailability is limited by solubility or dissolution rate, can act to increase their bioavailability ( , , ). The BCS divides drugs and drug candidates into classes based on their solubility and permeability characteristics ( , , )
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