Rheology of polyol behenates and drug release from matrix monolithic capsules.
Three polyol behenates with similar melting points (MP) and different hydrophilic-lipophilic balances (HLB) were studied (MP/HLB: 70/02, 63/05 and 57/13). After melting at MP+30 degrees C, the rheological behaviour of behenates was determined by adjustment of the rheograms to the Ostwald power-law and by statistical assessment of the flow index. Behenates showed slight shear thickening. This shear thickening increased when HLB of behenates decreased. This behaviour accounted for a reorganization of the particles under the shear, which became easier when the proportion of the polyethylene glycol chains in the wax decreased. Proxyphylline was used to prepare suspensions at a concentration of 25% in the melted behenates, and to manufacture monolithic capsules by cooling. The suspensions had a shear-thinning behaviour with or without thixotropy. Colloidal particles and aggregates formed in these suspensions directly influenced the rheological properties, as observation of solidified suspensions by scanning electron microscopy confirmed. Extended release of proxyphylline was obtained with the three waxes. Behenates 63/05 and 70/02 gave inert matrices and released drug very slowly. Hydrodispersible behenate 57/13 swelled and made up a kind of hydrophilic matrix that released proxyphylline more quickly, due to slight erosion. In the three cases, the release mechanism was basically diffusional in nature.
Duclos
R
R
Laboratory of Pharmaceutical Technology, Faculty of Medicine-Pharmacy, 76803, Rouen, France.
Bourret
E
E
Brossard
C
C
D000628:Aminophylline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D002214:Capsules; D005227:Fatty Acids / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013535:Suspensions; D013806:Theophylline / Q000031:analogs & derivatives; D014783:Viscosity
D002214:Capsules; D005227:Fatty Acids; D011108:Polymers; D013535:Suspensions; C024617:polyol; C003237:proxyphylline; D000628:Aminophylline; D013806:Theophylline; C007547:behenic acid