Titre du document / Document title

Pharmaceutical performance of solid dispersions containing poly(ethylene) glycol 6000 and diazepam or temazepam: Influence of grinding

Auteur(s) / Author(s)

VERHEYEN S. ⁽¹⁾ ; BLATON N. ⁽²⁾ ; KINGET R. ⁽¹⁾ ; VAN DEN MOOTER G. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Laboratorium voor Farmacotechnologie en Biofarmacie, K. U. Leuven Campus Gasthuisberg O+N, Herestraat 49, 3000 Leuven, BELGIQUE
⁽²⁾ Laboratorium voor Analytische Chemie en Medicinale Fysicochemie, K. U. Leuven, Van Evenstraat 4, 3000 Leuven, BELGIQUE

Résumé / Abstract

The effect of grinding on the physical properties and pharmaceutical performance of solid dispersions made of poly(ethylene) glycol 6000 (PEG6000) and temazepam or diazepam was studied using differential scanning calorimetry (DSC), X-ray powder diffraction and dissolution experiments. DSC-analysis of flash-cooled dispersions revealed that amorphous PEG present immediately after grinding crystallised upon aging mainly into the twice folded modification and to a small extent into the extended form. DSC-analysis of dispersions kept in the slab form for 1 month and subsequently ground, revealed that in the abscence of the grinding impulse crystallisation of PEG6000 takes place in the same way as in dispersions ground immediately after preparation and then aged for 1 month. Grinding solid dispersions immediately after preparation resulted in superior dissolution properties compared with solid dispersions kept in the monolith-slab form and subsequently ground. This difference in dissolution properties was found to be attributed to the drug and not to the polymer, more precisely, it was suggested that the drug particle size in ground dispersions was smaller than in dispersions kept in the slab form and subsequently ground. These findings suggest that grinding of solid dispersions immediately after preparation is the preparation method of choice instead of liquid filling of hard gelatin capsules resulting in monoliths.

Revue / Journal Title

Journal of thermal analysis and calorimetry   ISSN 1388-6150 

Source / Source

Congrès
PhandTA Symposium N^o7, Innsbruck , AUTRICHE (sd)
2003, vol. 73, n^o 2 [Document : 14 p.] (20 ref.), pp. 563-576 [14 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

Springer, Dordrecht, PAYS-BAS  (1998) (Revue)

Mots-clés anglais / English Keywords

Transmission electron microscopy ; Morphology ; Surface structure ; Differential scanning calorimetry ; Thermal analysis ; X ray diffraction ; Stability ; Polyethylene ; Drug carrier ; Control release polymer ; Dissolution ; Benzodiazepine derivatives ; Hypnotic ; Anticonvulsant ; Psychotropic ; Tranquillizer ; Temazepam ; Diazepam ; Solid dispersion ; Dosage form ; Physical properties ; Grinding(comminution) ; Fabrication property relation ;

Mots-clés français / French Keywords

Microscopie électronique transmission ; Morphologie ; Structure surface ; Calorimétrie différentielle balayage ; Analyse thermique ; Diffraction RX ; Stabilité ; Ethylène polymère ; Vecteur médicament ; Polymère vecteur ; Dissolution ; Benzodiazépine dérivé ; Hypnotique ; Anticonvulsivant ; Psychotrope ; Tranquillisant ; Témazépam ; Diazépam ; Dispersion solide ; Forme pharmaceutique ; Propriété physique ; Broyage ; Relation fabrication propriété ;

Mots-clés espagnols / Spanish Keywords

Microscopía electrónica transmisión ; Morfología ; Estructura superficie ; Análisis calorimétrico barrido exploración ; Análisis térmico ; Difracción RX ; Estabilidad ; Etileno polímero ; Vector medicamento ; Polímero vector ; Disolución ; Benzodiazepina derivado ; Hipnótico ; Anticonvulsivante ; Psicotropo ; Tranquilizante ; Temazepam ; Diazepam ; Dispersión sólida ; Forma farmacéutica ; Propiedad física ; Molienda ; Relación fabricación propiedad ;

Mots-clés d'auteur / Author Keywords

benzodiazepines ; dissolution ; DSC ; grinding ; poly(ethylene) glycol ; solid dispersion ; stability ; X-ray powder diffraction ;

Localisation / Location

INIST-CNRS, Cote INIST : 6367, 35400011432367.0140