Interactions of ketoprofen and ibuprofen with β-cyclodextrins in solution and in the solid state

• Published in: International journal of pharmaceutics Vol. 166; no. 2; pp. 189 - 203
• Main Authors: Mura, P, Bettinetti, G.P, Manderioli, A, Faucci, M.T, Bramanti, G, Sorrenti, M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 18-05-1998; Elsevier
• Subjects: 13C NMR; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chemically modified β-cyclodextrins; Differential scanning calorimetry; Dissolution rate; General pharmacology; Ibuprofen; Inclusion complexation; IR spectroscopy; Ketoprofen; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phase-solubility analysis; X-ray diffractometry; Differential scanning calorimetry; Chemically modified β-cyclodextrins; Inclusion complexation; Dissolution rate; X-ray diffractometry; Ibuprofen; 13C NMR; IR spectroscopy; Ketoprofen; Phase-solubility analysis; Complexation; Stability; Pharmaceutical technology; Oligosaccharide; Solubility; Molecular interaction; Drug carrier; Dissolution; Non steroidal antiinflammatory agent; Cyclodextrin; Arylacetic acid derivatives; Dosage form; Inclusion compound
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(98)00035-0

The complexing, solubilizing and amorphizing abilities towards ketoprofen and ibuprofen of native
β-cyclodextrin and some randomly substituted amorphous derivatives (methyl, hydroxyethyl, and hydroxypropyl
β-cyclodextrin with an average substitution degree per anhydroglucose unit, respectively of 1.8, 1.6 and 0.9) were determined and compared with those already observed for naproxen. Drug-carrier interactions were studied in aqueous solution by means of phase-solubility analysis and
13C NMR spectroscopy, and in the solid state using differential scanning calorimetry (DSC), X-ray powder diffractometry and infrared spectroscopy. The strength of the inclusion complexes with
β-cyclodextrins (
K
1:1,ibu>
K
1:1,nap>
K
1:1,keto) was directly related to the hydrophobic character of the guest (log
P values) and depended on its molecular features. The presence in physical mixtures of a high-energy state of crystalline drug molecularly dispersed in the amorphous carrier was assumed from DSC behaviour. Dissolution rates (dispersed amount method) of the active ingredient from equimolar drug-cyclodextrin physical mixtures and amorphous colyophilized products showed that methyl
β-cyclodextrin was the most effective carrier also for ketoprofen and ibuprofen.