Spray Dried Lubricants Offering Enhanced Flowability

Introduction

There are several approaches in order to develop tablet formulations. On the one hand, high functionality excipients that follow the concept “API+1” offer many advantages like easier handling, higher compactability and they combine synergistic effects. In addition, they eliminate the risk of segregation being homogeneous composites. On the other site, there are also good reasons for individual combinations of excipients. However, the limitations especially for continuous manufacturing are the non-flowability of lubricants. Aim of this study was to compare developmental spray dried lubricants against standard lubricants regarding flowability, lubrication efficiency and tablet hardness.

Material and methods

Sodium stearyl fumarate, SSF, (PRUV®), microcrystalline cellulose and carboxymethyl cellulose sodium (VIVAPUR® MCG 811P), microcrystalline cellulose, MCC, (VIVAPUR® 12 and 102), calcium hydrogen phosphate dihydrate, DCP (EMCOMPRESS®) and developmental spray dried lubricants based on MgSt and SSF (patent no.: US 11,925,707 B2) were provided by JRS Pharma GmbH & Co. KG (Rosenberg, Germany). Magnesium stearate, MgSt, (LIGAMED MF 2-V) was purchased from Peter Greven GmbH & Co. KG (Bad Münstereifel, Germany).

Powder Characteristic

Bulk density, angle of repose and FlodexTM were measured according to Ph. Eur. 2.9.34. and 2.9.36.

Tablet Formulations

The quantitative composition of the two formulations used for the tablet production is shown in Table 1.

*For testing the standard lubricants MgSt & SSF, 0.5 % lubricant was added to 29.5 % MCC and 70 % DCP
** For testing the standard lubricants MgSt & SSF, 1.5 % lubricant was added to 98.5 % MCC

Blending was performed using a freefall blender Brunimat Type Porta (Brunitec Suisse, Ermatingen, Switzerland). Formulation 1 was blended for 15 min. Subsequently, the spray dried lubricant or standard lubricant was added and blended for another 3 min. For formulation 2, the spray dried lubricant or standard lubricant was blended both for 3 min and for 60 min. The speed of the freefall blender was at 24 rpm.

Tableting

Both formulations were compacted into biplane tablet with a diameter of 13 mm using the rotary tablet press of the type Pressima from the manufacturer IMA Kilian (Köln, Germany). Filling depth was set to 10 mm for formulation 1; tablet weight was set to 400 mg for formulation 2.

Functional Tablet Characteristics

Tablet hardness was measured with model TBH 425 TD from Erweka GmbH (Langen, Germany) according to Ph. Eur. 2.9.8.

Results and discussion

Powder Flowability

Spray dried lubricants, both based on MgSt and SSF, showed a great improvement in flowability. Angle of repose decreased from > 50 ° to < 30 ° for the spray dried lubricants (Figure 1).

Flodex diameter was measured to be 18 mm for spray dried magnesium stearate in comparison to 24 mm for
standard MgSt. For spray dried sodium stearyl fumarate, flodex diameter was at 10 mm in comparison to 34 mm for
standard SSF (Figure 2).

Bulk density increased for both spray dried MgSt and spray dried SSF in comparison to the standard lubricant.
Results are shown in Table 2:

Lubrication Efficiency

Ejection force for formulation 1, based on calcium hydrogen phosphate dihydrate, was analyzed for several compression forces up to 40 kN. Without adding a lubricant, ejection force rose to > 1000 N. Adding 0.5 % standard lubricant or 0.71 % spray dried lubricant resulted in a decrease of the ejection force to 400 N at 40 kN compression force. Standard lubricant and spray dried lubricants resulted in similar ejection force values (Figure 3).

Tablet Hardness

Tablet hardness was analyzed with formulation 2, based on microcrystalline cellulose. Using a spray dried lubricant resulted in a higher tablet hardness in comparison to the standard lubricant. After an extended blending time of 60 min, the loss in tablet hardness remained constant for the standard lubricant and its spray dried version. However, the effect of overblending was significantly lower for the lubricant based on SSF in comparison to the lubricant based on MgSt. Results are summarized in Table 3:

Conclusion

Spray dried lubricants, both based on MgSt and SSF, offer excellent flowability (angle of repose < 30 °) that enables constant feeding for continuous manufacturing. Lubrication efficiency, analyzed in a challenging formulation with calcium hydrogen phosphate dihydrate, is evaluated to be equivalent for standard lubricants and spray dried lubricants. With a formulation based on MCC, tablet hardness was measured to be higher for spray dried lubricants.

See the full technical brochure on Spray Dried Lubricants Offering Enhanced Flowability here

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Source: JRS Pharma, technical brochure “Spray Dried Lubricants Offering Enhanced Flowability”

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