Effects of blender rotational speed and discharge on the homogeneity of cohesive and free-flowing mixtures.

The roles of blender rotational speed and blender discharge on the homogeneity of free-flowing art sand and of a cohesive placebo formulation were investigated in the tote blender. For three practical operating speeds, 6, 10, and 14 RPM, spanning the entire range of commercial equipment, the homogeneity of the free-flowing mixture was independent of rotational speed and blender size. On the other hand, the homogeneity of the cohesive pharmaceutical powder mixture was dependent on vessel rotational speed in a complex fashion, with 10 RPM producing a better final mixture than either 5 or 15 RPM. The homogeneity of the free-flowing sand mixture was preserved when discharged into a vertical bin, while the homogeneity of the fine pharmaceutical powder mixture significantly improved after discharge from the tote blender.

A novel nuclear magnetic resonance (NMR) imaging method for measuring the water front penetration rate in hydrophilic polymer matrix capsule plugs and its role in drug release.

An NMR imaging method was developed to estimate the rate of water movement in slow-release capsule matrices of pseudoephdrine HCl and hydroxypropyl cellulose (HPC). Test capsules were first placed in a USP method 2 (paddles, 50 rpm) dissolution apparatus. Each plug was removed from the dissolution medium at predetermined times, blotted dry, and placed within the magnetic field of a General Electric 400-MHz wide-bore NMR spectrometer equipped with a microimaging accessory. Images were recorded along the transverse plane of each plug. The water penetration rate was determined by comparison of the cut and weighed contour plots of the images acquired. After 1 hr, the plugs tamped to 200 N exhibited water penetration to the center, while only 45% of the drug was released. The percentage dry matrix was fitted to the Jost equation to obtain a diffusion coefficient of 4.15 x 10(-6) cm2/sec. NMR imaging is set forth as an important and practicable technique to investigate drug formulations. In the HPC matrix system of this study, the NMR imaging results convincingly revealed the rate of hydration front penetration not to be a rate-limiting step in the drug release process.

Sustained-release oral delivery of theophylline by use of polyvinyl alcohol and polyvinyl alcohol-methyl acrylate polymers.

Crystalline polyvinyl alcohol (PVA) polymer and low-crystallinity polyvinyl alcohol-methyl acrylate copolymer (PVA-MA) were examined as sustained-release tablet excipients with theophylline as a model drug. By blending of different proportions of the crystalline polymer and the low-crystallinity copolymer, it was possible to affect the release characteristics of the tablets. Tablets made with crystalline PVA provided instant release of theophylline in vitro. Tablets made with a larger proportion of PVA-MA relative to PVA provided a very prolonged release profile in vitro. A formulation containing PVA-MA:PVA:theophylline in a ratio of 1:9:10 provided sustained-release profiles in vitro and in vivo in dogs. The dissolution release profile of this PVA-blend tablet formulation in vitro agreed extremely well with the percentage of bioavailable dose absorbed over time in vivo. The formulation provided a plateau of levels in plasma over 16 h. The oral bioavailability of theophylline from this formulation in dogs was approximately 80% and was equivalent to that obtained after administration of Theo-Dur, a marketed extended-release theophylline tablet from Key Pharmaceuticals.