Effect of Magnesium Stearate Lubrication on the Tableting of Spray-dried Grades of Mannitol and Fluid-Bed Granulated Grades of I

This poster was presented at the ECP 2025 in Porto

Introduction

Polyols, such as mannitol, sorbitol, and isomalt, are widely used as excipients for tablet direct compression formulations because of their excellent compaction properties, flowability, as well as high and pH independent solubility.
There are different grades on the market that are represented by milled and classified crystalline, granular, or spray-dried material.
Having different chemical and morphological differences, the tableting process and compaction properties of polyols can change drastically as a function of lubricant amount.
This study aimed to investigate the effect of magnesium stearate amount on the tableting of spray-dried grades of mannitol and fluid-bed granulated grades of isomalt.

Methods

Samples of powder were prepared in the same way. Magnesium stearate was sieved through 0.5 mm mesh size sieve. PEARLITOL® 200 SD or Mannogem® XL Opal SD or galenIQ 721 were mixed with specific amount of magnesium stearate (0.5, 2.0, 2.5, or 3.0 wt.%) for 2.5 min in a double-cone blender (DVC Developer; Comasa, Barcelona, Spain). To improve microscopic homogeneity, the obtained mixture was sieved through the sieve with 1 mm mesh-size and then mixed again for 2.5 min.
Tableting cycles simulated the movement of small rotary press punches. In accordance with STYL’One Nano presetting’s, the simulated small rotary press has a turret diameter of 180 mm, precompression roll diameter of 44 mm, angle between rollers of 65 degrees, compression roll diameter of 160 mm, angle between main compression and the beginning of the compression ramp of 60 degrees, an angle of ejection ramp of 20 degrees. Used tableting speed simulated 70 rpm (maximum for STYL’One Nano). Used pre-compression force of 5 kN (50 MPa) and a compression force of 10 and 30 kN (100 and 300 MPa) were applied.
Powder mixtures were tableted with round flat tooling (diameter of 11.28 mm) to obtain a target mass of 500 mg using a STYL’One Nano (MEDELPHARM, Beynost, France) compaction simulator. Powder feeding into the die was performed automatically via the feed shoe.

The tablet height (l), diameter (d), and tablet crushing strength (hardness or breaking force, F) were measured (n=10) using a tablet tester (ST50 WTDH; SOTAX AG, Aesch, Switzerland) immediately after compaction.
The particle size distribution as well as the D10%, D50%, and D90% were determined by a laser diffraction particle size analyser using an Aero S module for dry dispersions (Mastersizer 3000, Malvern Instruments, UK) at the specified settings: feed rate of 30-80%;hopper gap of 1.0-1.5 mm; air pressure of 2.0 bar. Approximately 10–15 g of the sample was used for each repetition (n=3).
Specific surface area of excipients was measured using BET method from isotherms of low-temperature nitrogen adsorption–desorption at 77°K (Nova 4200e; Quantachrome, Boynton Beach, FL, USA).
Powder X-ray Diffraction (pXRD) Analysis was conducted on a diffractometer (Rigaku Miniflex 600C; Rigaku Co., Tokyo, Japan) in θ/2θ geometry at ambient temperature using CuKα X-radiation (λ = 1.54182 Å) at 40 kV and 15 mA power. X-ray diffraction patterns were collected over the 2θ range of 3–60◦ at a 5◦/min scan rate.

Materials

Spray dried grades of mannitol – PEARLITOL® 200 SD (#EQ98Q; Roquette, Lestrem, France) and Mannogem® XL Opal SD (#122403728; SPI Pharma, Wilmington, USA)
Isomalt – galenIQ 721 (#L121390741) and galenIQ 720 (#L1212919U1; BENEO – Palatinit GmbH, Obrigheim/Pfalz, Germany)
Magnesium Stearate (MgSt; #299546; Magnesia 4264; Magnesia GmbH, Lüneburg, Germany)

Results

Different morphology (Fig. 1), particle size distribution (Fig. 2); highly crystallinity (Fig. 3)
Specific surface area (BET method): PEARLITOL® 200 SD (0.988) > Mannogem® XL Opal SD (0.911) > galenIQ 720 (0.837) > galenIQ 721 (0.709 msq/g).
Moisture content for PEARLITOL® 200 SD, Mannogem® XL Opal SD, galenIQ 720, and galenIQ 721 comprised 0.9±0.1, 0.8±0.0, 5.0±0.2, and 2.9±0.1 wt. %.
Bulk and tapped density: PEARLITOL® 200 SD > galenIQ 720 > Mannogem® XL Opal SD > galenIQ 721 (Fig. 4)
@ 0.5 wt.% of MgSt, the ejection force of PEARLITOL® 200 SD was too high [Ref.4] (Fig. 5) and thus it was not investigated
@ 3.0 & 0.5 wt.% of MgSt, the ejection force of galenIQ 720 & 721 was below 300 N (Fig. 6-9)
The ejection force of “Mannogem® XL Opal SD” increased with compression force increase and MgSt concentration decrease (Fig. 6-9)
@ 3.0 wt.% of MgSt and for both compression pressure (100 and 300 MPa), the ejection force: galenIQ 720 ≈ galenIQ 721 < Mannogem® XL Opal SD < PEARLITOL® 200 SD (Fig. 7 & 9)
For all excipients, tablet hardness increased along with the increase in compression force (Fig. 10 & 11)
Tablet hardness: galenIQ 721 > galenIQ 720 > PEARLITOL® 200 SD > Mannogem® XL Opal SD (Fig. 11)

Conclusion

PEARLITOL® 200 SD, Mannogem® XL Opal SD, galenIQ 720, and galenIQ 721 were compared in terms of ejection force and ejection force development upon tableting at two levels (0.5 & 3.0 wt.%) of MgSt.
At both levels of MgSt and 100 & 300 MPa of compression pressure, isomalt galenIQ 720 and galenIQ 721 demonstrated the lowest (below 300N) and the same ejection force and superior tablet hardness.
Comparably lower specific surface areas of galenIQ 720 and galenIQ 721 can explain their lower ejection force.

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Effect of Magnesium Stearate Lubrication on the Tableting of Spray-dried Grades of Mannitol and Fluid-Bed Granulated Grades of Isomalt

Source: Valentyn MOHYLYUK, Kirils KUKULS, Alīna Jaroslava FROLOVA, Zoltán Márk HORVÁTH, Elzbieta Maria GNIAZDOWSKA, Līga PĒTERSONE, Effect of Magnesium Stearate Lubrication on the Tableting of Spray-dried Grades of Mannitol and Fluid-Bed Granulated Grades of Isomalt, 5th European Conference on Pharmaceutics, 2025 ECP 2025 in Porto, Riga Stradinis University Leading Research Group Faculty of Pharmacy

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