Rheological behavior of drug suspensions in Gelucire mixtures and proxyphylline release from matrix hard gelatin capsules.
Mixtures of Gelucires 50/02 and 50/13 showing different hydrophilic-lipophilic balances (HLB) and of proxyphylline were used to prepare suspensions at a concentration of 25% and to manufacture extended release hard gelatin capsules by cooling. The rheological behaviors of Gelucire mixtures with and without drug were determined by adjustment of the rheograms to the Ostwald power-law and by statistical assessment of the flow index. Pure Gelucire mixtures were very slightly shear thickening whereas proxyphylline suspensions had a thixotropic shear thinning behavior. These rheological behaviors can be explained by the chemical composition and by the ratio of the two Gelucires used. Extended release of proxyphylline was obtained with all these mixtures. Drug release increased with Gelucire mixture HLB owing to higher erosion. A viscosity-release relationship was found and allowed, with these two Gelucires of extreme HLB and viscosities, to define the formulations which will give an optimal drug release, by the determination of their suspension viscosity. Modeling of dissolution kinetics has generally shown the predominance of surface erosion of the plugs relative to drug diffusion inside the matrix. This was confirmed by the better linearization of percentage released, according to Hixson-Crowell as compared with Higuchi.
Ratsimbazafy
V
V
Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Limoges, France.
Bourret
E
E
Duclos
R
R
Brossard
C
C
D000628:Aminophylline / Q000031:analogs & derivatives* / Q000737:chemistry; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004058:Diffusion; D005079:Excipients / Q000737:chemistry*; D005223:Fats / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D009821:Oils / Q000737:chemistry*; D012212:Rheology; D013499:Surface Properties; D013535:Suspensions; D013806:Theophylline / Q000031:analogs & derivatives; D014783:Viscosity
D002214:Capsules; D003692:Delayed-Action Preparations; D005079:Excipients; D005223:Fats; D008055:Lipids; D009821:Oils; D013535:Suspensions; C071183:Gelucire 50-02; C003237:proxyphylline; D000628:Aminophylline; D005780:Gelatin; D013806:Theophylline