Experimental and Statistical Studies in the Development of Ketoprofen–Hydroxypropyl-β-Cyclodextrin Inclusion Complexes for Application in Compressed Tablets
Monica Stamate Cretan, Lacramioara Ochiuz, Camelia-Elena Iurciuc-Tincu, Carmen Anatolia Gafițanu, Alexandra Barsan (Bujor), Mousa Sha’at, Ciprian StamateKetoprofen is a Biopharmaceutics Classification System (BCS) class II non-steroidal anti-inflammatory drug whose therapeutic performance is limited by its poor aqueous solubility, though complexation with cyclodextrins is a well-established strategy to overcome this limitation. The aim of this work was to prepare and characterize inclusion complexes of ketoprofen with HPβCD. Complexes were obtained by the solution (magnetic-stirring) method at ketoprofen–HPβCD molar ratios of 1:1 and 2:1 and were characterized by Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) coupled with EDX, and computer-assisted dimensional analysis and statistics (AutoCAD/MathCAD). The bulk and tapped densities were used to derive the Carr index and the Hausner ratio, respectively. FT-IR showed attenuation and shifting of the characteristic C=O, C=C, and –CH bands of ketoprofen and the presence of the 1655 cm−1 band in complexes demonstrates inclusion. DSC revealed a marked reduction of the ketoprofen melting endotherm, the degree of inclusion reaching 75% (1:1) and 62% (2:1). SEM and statistical analysis confirm, individualized particles, predominantly 20–100 µm in perimeter size. The dissolution test showed a faster release of the complexes than in the case of pure ketoprofen. Therefore, HPβCD forms stable inclusion complexes with ketoprofen having pharmacotechnical properties suitable for compressed tablets.