Physicochemical characterization of solid dispersions of three antiepileptic drugs prepared by solvent evaporation method.
We have investigated the solid dispersion and dissolution profiles of three antiepileptic drugs (carbamazepine (CBZ), oxcarbazepine (OXC) and rufinamide (RFN)) with different aqueous solubilities, prepared by the solvent evaporation method. Solid dispersions of the three drugs in hydroxy-propylmethylcellulose (HPMC), with drug:polymer ratios of 1:4, were prepared and characterized by differential scanning calorimetry (DSC), Fourier transformation infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy. The release mechanism was also investigated and the kinetic order of the solid dispersions was evaluated. It appeared that the dissolution behaviour depended on the physicochemical properties of the drug and drug-polymer interactions. DSC thermographs showed amorphous forms for all drugs confirmed by XRD patterns. The FTIR spectra of CBZ and OXC demonstrated drug interactions with HPMC through hydrogen polymer bonds. Thus, solid dispersions of these drugs had an improved dissolution profile. In contrast, solid dispersions of RUF showed modest enhancement of dissolution, suggesting negligible drug-polymer interactions. The different dissolution behaviour is attributed to the extent of interactions between the polymer hydroxyl group and the drug amide groups.
Douroumis
Dionysios
D
Phoqus Pharmaceutical Ltd, 10 Kings Hill Avenue, Kings Hill, West Malling, ME19 4PQ, Kent, UK. dionysios.douroumis@phoqus.com
Bouropoulos
Nikolaos
N
Fahr
Alfred
A
D000927:Anticonvulsants / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry; D006860:Hydrogen Bonding; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D000078330:Oxcarbazepine; D012995:Solubility; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D014230:Triazoles / Q000737:chemistry*; D017155:Wettability; D014961:X-Ray Diffraction
D000927:Anticonvulsants; D004337:Drug Carriers; D012997:Solvents; D014230:Triazoles; D002220:Carbamazepine; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D000078330:Oxcarbazepine; C079703:rufinamide