Scale-up of a high shear wet granulation process using a nucleation regime map approach

Scale-up of the high shear wet granulation （HSWG） process is considered a challenge because HSWG is complex and influenced by numerous factors, including equipment, formulation, and process variables. For a system of microcrystalline cellulose and water, HSWG experiments at three scales （1, 2, and 4 L working vessel） were conducted with a granulator. Scale-up was implemented on the basis of a nucleation regime map approach. To keep dimensionless spray flux and drop penetration time constant, water addition time at three processing scales were 300, 442, and 700 s, respectively. The other process parameters were kept unchanged. Granule size distributions were plotted and compared, and scanning electron microscopy was used to analyze granule surface morphology. Physical characterization was undertaken using a modified SeDeM method. At nearly all scales, granule yield was greater than 85% and all the cosine values were larger than 0.89. At the same experiment points, granules at all scales had similar surface morphology and similar physical characteristics. The results demonstrate that a rational scaling-up of the HSWG process is feasible using a regime map approach.

Preparation of solid pharmaceutical forms of celecoxib with immediate-release and sustained-release by using wet granulation techniques and evaluation of their in vitro characteristics

In the present study,we aimed to formulate matrix tablets of celecoxib with immediate-release(IR)and sustained-release(SR)and evaluate the influence of different types and concentrations of polymers on drug release characteristics in vitro.All formulations were prepared by using the wet granulation technique.One formulation(F5)with the traditional release was composed without release-control polymers.In contrast,four formulations(F1–F4)with prolonged action were designed by using different cellulosic polymers,such as hydroxypropyl methylcellulose polymers(HPMC-K100M and HPMC-Е6),hydroxypropyl cellulose with high viscosity grade(HPCh),carboxymethyl cellulose(CMC),and ethylcellulose(EC-10 cps).All tablet formulations contained sodium lauryl sulfate(SLS),polyvinylpyrrolidone(PVP-k30),microcrystalline cellulose(MCC),and lactose monohydrate.The MCC and PVP-k30 were used in a fixed quantity in all formulations except for formulation F5,which contained 10%and 2.7%of them,respectively.The effects of polymer viscosity grade and its quantity on celecoxib release from two formulations containing the same polymer were studied.Drug release in vitro was evaluated in phosphate buffer(pH=7.4).The amount of celecoxib released in phosphate medium was calculated by preparing a standard series.In vitro profile indicated that formulations F1(HPMC-K100M)and F2(HPMC-E6)extended the drug release for 18 h(82%)and 10 h(96.001%),respectively.Formulations F3and F4 released 72.09%and 59.8%of their contents during 18 h,respectively,and thus their effects could last for more than a day.However,IR formulation(F5)released more than 90%of its content within 1–2 h.MS Excel was used to analyze the dissolution profile data for drug release kinetics,such as first-order,Zero-order,Higuchi,and Korsmeyer-Peppas models.The release mechanism of all formulations was CaseⅡrelaxation release.This study showed that cellulosic derivative polymers could successfully prolong IR of matrix tablet formulation.

Analysis of mesoscale effects in high-shear granulation through a computational fluid dynamics-population balance coupled compartment model

There is a need for mesoscale resolution and coupling between flow-field information and the evolution of particle properties in high-shear granulation. We have developed a modelling framework that com- partmentalizes the high-shear granulation process based on relevant process parameters in time and space. The model comprises a coupled-flow-field and population-balance solver and is used to resolve and analyze the effects of mesoscales on the evolution of particle properties. A Diosna high-shear mixer was modelled with microcrystalline cellulose powder as the granulation material. An analysis of the flow-field solution and compartmentalization allows for a resolution of the stress and collision peak at the impeller blades. Different compartmentalizations showed the importance of resolving the impeller region, for aggregating systems and systems with breakage. An independent study investigated the time evolution of the flow field by changing the particle properties in three discrete steps that represent pow- der mixing, the initial granulation stage mixing and the late stage granular mixing. The results of the temporal resolution study show clear changes in collision behavior, especially from powder to granular mixing, which indicates the importance of resolving mesoscale phenomena in time and space.

Process optimization for the enhanced stability of diclofenac potassium granules and capsules

This study aimed to investigate the effects of different process parameters on the physical properties, in vitro dissolution rate, and short and long-term stability of diclofenac potassium（DFP） granules and capsules. DFP granules exhibited low total amounts of impurities when prepared through the wet granulation method using a granulating solvent with a low water/ethanol ratio. The impurities of the wet DFP mass dried at 70 ℃ were higher than those dried at 50 ℃ or 60 ℃. DFP granules were stable under strong light exposure during preparation. DFP granules prepared using a granulating solvent with a 1：4 water/ethanol ratio had a relatively smaller particle size and higher angle of repose than those prepared using granulating solvents with other water/ethanol ratios. The dissolution rate of DFP capsules prepared using four different water/ethanol ratios was less than 2% after 10 min of dissolution and increased to 95% within 30 min of dissolution. The total amount of drug impurities of DFP capsules prepared using a granulating solvent with 1：4 water/ethanol ratio was considerably lower than those of DFP capsules prepared using a granulating solvent with a 1：0 water/ethanol solvent ratio. Regardless of the water/ethanol ratio, the capsules showed poor stability when exposed to high temperature（60 ℃） and strong light（4500±500 Lux） for 10 days, but were relatively stable at high humidity（92.5% RH）. The results of the long-term stability（25±2 ℃ and 60%±10% relative humidity） study showed that DFP granules were more stable than DFP capsules, and were stable for 12 months. The type of encapsulating material did not affect the 2-month stability of DFP. DFP granules are sensitive to granulating solvent and drying temperature and DFP capsules should be stored away from high temperature and strong light.

VISCOUS FORCES BETWEEN TWO SPHERES COLLIDING THROUGH INTERSTITIAL POWER-LAW FLUID

Interaction between two spheres with an interstitial fluid is essential in Discrete Element modeling for simulating the behaviors of 'wet' particulate materials. In this paper the interaction between two spheres with an interstitial Power-law fluid was approximately resolved as normal and tangential interactive models respe ctively, for which the governing equations were simplified on the basis of Reynolds approximation. These equations were then solved analytically together with the boundary conditions to obtain the pressure distributions for each individual model, and event u-ally solutions of the viscous squeeze force and the tangential viscous resistance were obtained, which provide a set of solutions for implementing into DEM code or other purposes.