Lubrication of Direct-Compressible Blends with Magnesium Stearate Monohydrate and Dihydrate - Pharmaceutical Technology

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Lubrication of Direct-Compressible Blends with Magnesium Stearate Monohydrate and Dihydrate
The influence of magnesium stearate (MgSt) on powder lubrication and finished solid-dose properties presents big challenges to drug manufacturers.

Pharmaceutical Technology

The blends were compressed using a 10-station instrumented tablet press (Natoli Engineering, St Louis, MO) with 0.4375-in. standard round, concave tooling. All tablets were compressed to target hardness of 8.0 kp using a hardness tester (Pharmatest, Piscataway, NJ), and target weight of 500 mg was measured using a bench scale (Sartorius, New York, NY). Tablet press speed was maintained at 17 rpm. Tablet friability limit was set at not more than (NMT) 0.8% using a friability tester (Pharmatest). Lubrication performance and influence on the tablets' physical attributes were evaluated on the basis of the main compression force, precompression force, ejection force, and tablet knock-off using a real-time data acquisition tool (Natoli Engineering, St. Louis, MO). In vitro dissolution studies were conducted according to USP Method, and a similarity factor, f 2, was derived for comparative analysis. Data analysis was conducted using a statistical tool ("Minitab," Minitab Inc., State College, PA).

Solid-state characterization of MgSt hydrates. Solid-state characterization of MgSt hydrates was conducted at particle level using a particle-size analyzer, and at molecular level using DSC, powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM).

Powder X-ray diffraction. PXRD patterns of samples were measured with a Siemens D500 X-ray diffractometer over the range of 2q = 2 to 40 and a 0.02 step size.

Scanning electron microscope. The morphologies of the samples were investigated using a scanning electron microscope (model S-4500, Hitachi, Japan). A Cressington 108 Auto/SE sputter coater was used (Cressington Scientific, Watford, UK). Images were captured with the secondary electron detector. A small portion of the powdered sample was distributed onto a conductive carbon adhesive disk on SEM stubs for SEM imaging. The specimens were sputter coated with gold–palladium to impart conductivity. The instrumental parameters were: electron beam source = W filament; accelerating voltages = 15 kV; objective aperture = 50 μm (aperture #3); vacuum mode = high vacuum; imaging detector(s): SE; magnification = 1000, 2500, and 3500; specimen tilt = 0.0; and working distance = nominal 16.

Particle-size distribution and percent water. Particle-size distributions were determined using a laser diffraction system (series 2600, Malvern Instruments Ltd., Malvern, UK) equipped with a 63-mm lens (size range of 1.2–118 μm) and a stirred cell.

Differential scanning calorimetry. Differential scanning calorimetry (Q100 DSC, TA Instruments, New Castle, DE) was done between temperatures from –60 to +190 C at a heating rate of 2 C/min and a nitrogen purge of 50 mL/min. Samples (3–5 mg) were tested in crimped-aluminum pans, and an empty pan was used as a reference. The temperature axis and cell constant of DSC were previously calibrated with pure standard of indium. Data acquisition and analysis were conducted using TA Instruments software.

Thermal gravimetric analysis. Thermal gravimetric analysis (Q50 TGA, TA Instruments) was carried out from 25 to 190 C at a heating rate of 5 C/min. Data acquisition and analysis were conducted using TA Instruments software.

Near infrared spectroscopy. NIR spectral analysis (NIR analyzer, Thermo Fisher Scientific, Waltham, MA) was conducted using standard mixtures having known composition of MgSt monohydrate and dihydrate prepared from 92.0% MgSt-M and 95.4% MgSt-D stock material.

Blend homogeneity. Effusivity sensor suitability with baseline run was conducted using neat microcrystalline cellulose, NF to enable the effusivity sensors to predict homogeneity via in-line and real-time measurement. The placebo material was blended for a specified duration, and the synchronization pulse with baseline was established for the effusivity sensors.


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