RESUMO
OBJECTIVES: Formulations of over the counter (OTC) NSAIDs differ substantially, but information is lacking on whether this alters their gastrointestinal profiles. To assess disintegration and dissolution rates and pharmacokinetics of four preparations of OTC ibuprofen and relate these with spontaneously reported gastrointestinal adverse events. METHODS: Disintegration and dissolution rates of ibuprofen tablets as (a) acid, (b) sodium salt, (c) lysine salt, and (d) as a liquid gelatine capsule were assessed. Pharmacokinetic data gastrointestinal and spontaneously reported adverse events arising from global sales were obtained from files from Reckitt Benckiser. KEY FINDINGS: Disintegration at low pH was progressively shorter for the preparations from a-to-d with formation of correspondingly smaller ibuprofen crystals, while dissolution was consistently poor. Dissolution at a neutral pH was least rapid for the liquid gelatine capsule. Pharmacokinetic data showed a shorter tmax and a higher Cmax for preparations b-d as compared with ibuprofen acid. Spontaneously reported abdominal symptoms were rare with the liquid gelatine preparation. CONCLUSIONS: The formulations of OTC ibuprofen differ in their disintegration and dissolution properties, pharmacokinetic profiles and apparent gastrointestinal tolerability. Spontaneously reported abdominal symptoms were five times lower with the liquid gelatine capsule as compared with ibuprofen acid despite a 30% increase in Cmax .
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Ibuprofeno/farmacocinética , Medicamentos sem Prescrição/farmacocinética , Administração Oral , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Disponibilidade Biológica , Composição de Medicamentos , Liberação Controlada de Fármacos , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Ibuprofeno/administração & dosagem , Ibuprofeno/efeitos adversos , Ibuprofeno/química , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Medicamentos sem Prescrição/administração & dosagem , Medicamentos sem Prescrição/efeitos adversos , Medicamentos sem Prescrição/química , Solubilidade , Equivalência Terapêutica , Adulto JovemRESUMO
The synthesis and characterisation of a series of liquid-crystalline aromatic-aliphatic copolyesters are presented. Differential scanning calorimetry showed these polymers have a glass transition temperature in the range 72 degrees C-116 degrees C. Polarised optical microscopy showed each polymer exhibits a nematic mesophase on heating to the molten state at temperatures below 165 degrees C. Melt processing is demonstrated by the production of injection moulded and compression moulded specimens with Young's modulus of 5.7 +/- 0.3 GPa and 2.3 +/- 0.3 GPa, respectively. Wide-angle X-ray scattering data showed molecular orientation is responsible for the increase of mechanical properties along the injection direction. Degradation studies in the temperature range 37 degrees C-80 degrees C are presented for one polymer of this series and a kinetic constant of 0.002 days(-1) is obtained at 37 degrees C assuming a first order reaction. The activation energy (83.4 kJ mol(-1)) is obtained following the Arrhenius analysis of degradation, showing degradation of this material is less temperature sensitive compared with other commercially available biodegradable polyesters. In vitro and in vivo biocompatibility data are presented and it is shown the unique combination of degradative, mechanical and biological properties of these polymers may represent in the future an alternative for medical device manufacturers.
Assuntos
Materiais Biocompatíveis , Hidrocarbonetos Aromáticos/química , Cristais Líquidos/química , Poliésteres , Polímeros , Células 3T3 , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Humanos , Masculino , Teste de Materiais , Camundongos , Estrutura Molecular , Peso Molecular , Poliésteres/síntese química , Poliésteres/química , Poliésteres/metabolismo , Polímeros/síntese química , Polímeros/química , Polímeros/metabolismo , Ratos , Ratos Sprague-Dawley , Espalhamento de Radiação , Estresse Mecânico , Temperatura , Técnicas de Cultura de TecidosRESUMO
This paper describes the micro-fabrication and preliminary assessment of a miniature polydimethylsiloxane (PDMS) device for performing rapid, parallel liquid phase chromatographic separations driven by centrifugal force in microchannels. Device components include a main separating channel, into which a high performance liquid chromatography (HPLC) particulate stationary phase was packed under pressure by application of centrifugal force, in addition to solvent and sample reservoirs. Also described are methods for sealing such devices based upon partial polymerisation of PDMS. The mobile phase flow rate through a typical device was measured and several important chromatographic parameters determined from a test separation. An expression describing mobile phase flow through packed channels was also developed, based upon work on liquid flow in open micro-channels. Good agreement between predicted and measured flow rates were observed. Some predictions for potential uses of such devices and possibilities for further miniaturisation are discussed.
