docTechnical Bulletin Lubripharm® SSF Sodium Stearyl Fumarate, NF
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Technical Bulletin Lubripharm® SSF Sodium Stearyl Fumarate, NF
Technical Bulletin Lubripharm® SSF Sodium Stearyl Fumarate, NF Lubripharm Sodium Stearyl Fumarate (SSF) is an inert, less hydrophobic alternative to magnesium stearate as a pharmaceutical tablet lubricant. Tablets made with Lubripharm SSF exhibit less sensitivity to variations in blending time and lubricant levels and have functionally superior hardness characteristics compared to tablets produced with magnesium stearate. In addition, Lubripharm SSF does not exhibit incompatibility with active pharmaceutical ingredients (APIs) that are susceptible to oxidation or degradation in alkaline conditions, or contain primary amines. Lubripharm SSF is a lubricant used in capsule or tablet formulations. SSF has superior performance when compared to magnesium stearate: • Higher tablet hardness • Lower ejection forces • Less impact on disintegration times, which is especially important for orally disintegrating tablets • Less sensitive to overblending • Less residue in solution than magnesium stearate makes it more effective for effervescent applications Compactibility studies comparing Lubripharm SSF to magnesium stearate showed that Lubripharm SSF was superior with regard to the functional impact on tablet hardness, ejection force, friability, and disintegration time. Figure 1: Lubripharm or Mg Stearate as Lubricants - Mannogem EZ Carrier Blend Time Study Figure 1: Lubripharm ororMg Lubricants- Mannogem - Mannogem EZ Carrier MgStearate Stearate as Lubricants EZ Carrier 16 Lubripharm Tablet Hardness (kp) Tablet Hardness (kp) Spray Dried Mannitol (Mannogem® EZ) was blended for 5 and 10 min. with Lubripharm SSF or magnesium stearate at a 2.0% level and compressed at 15, 20, 25, 30, and 35 kN. Results (Figure 1) showed that the tablet hardness for the magnesium stearate blends was 1-2 kp less than the Lubripharm SSF blends over the compaction profile. 18 Figure 1: Effect of Blend Time on Tablet Hardness Using 2% 18 14 16 12 14 10 12 8 Lubripharm SSF 5 min. Blend 10 6 Mg Stearate 5 min. Blend Lubripharm 5 min. Blend Mg StearateSSF 10 min. Blend Lubripharm SSF 10 min. Blend Lubripharm SSF 10 min. Blend 84 10000 6 14000 18000 22000 Mg Stearate 5 min. Blend 26000 30000 34000 30000 34000 Mg Stearate 10 min. Blend Compression Force (N) 4 10000 14000 18000 22000 26000 Compression Force (N) Figure 2:2:Effect of Blend Time on Ejection Force Using 2% Figure Lubripharm oror Mg Lubricants- Mannogem - Mannogem EZ Carrier Lubripharm MgStearate Stearate as as Lubricants EZ Carrier 600 Figure 2: Lubripharm SSF 5 min. Blend or Mg Stearate as Lubricants - Mannogem EZ Carrier 550Lubripharm Lubripharm SSF 10 min. Blend Ejection Force (N)Force (N) Ejection The ejection forces (Figure 2) for the magnesium stearate blends were 50 to 150 newtons higher than blends containing Lubripharm SSF. Lower ejection force reduces the attrition to the tablet during ejection, which can result in destruction of tablet bonding, leading to tablet capping and tablet lamination. 500 600 450 550 400 500 350 450 Mg Stearate 5 min. Blend Lubripharm 5 min. Blend Mg StearateSSF 10 min. Blend Lubripharm SSF 10 min. Blend Mg Stearate 5 min. Blend Mg Stearate 10 min. Blend 300 400 250 350 200 300 10000 250 200 10000 14000 18000 22000 26000 30000 34000 30000 34000 Compression Force (N) 14000 18000 22000 26000 Compression Force (N) Figure 3: and Magnesium Stearate as Lubricants - Mannogem TM EZ Carrier-12 kp. e 1: arm or Mg Stearate as Lubricants - Mannogem EZ Carrier 8:24 14000 14000 Prolonged mixing with magnesium stearate can result in a reduction in dissolution rate, due to the excessive coating of granules by this highly hydrophobic lubricant. Improving disintegration time essential in the design Lubripharm SSF 5is min. Blend of ODT-based systems, well as systems Lubripharm SSF 10 min.as Blend Mg Stearate 5 min. Blend containing BCS Class II and Class IV APIs. The Mg Stearate 10 Blend Lubripharm SSFmin. 5 min. Blend greater hydrophobicity of magnesium stearate Lubripharm SSF 10 min. Blend leads to increased disintegration times (Figure 18000 22000 26000 Mg Stearate 5 30000 min. Blend 34000 3), as compared to tablets manufactured with Compression ForceMg (N)Stearate 10 min. Blend Lubripharm SSF. 18000 22000 26000 30000 Figure 3:Figure Effect3:ofLubripharm Blend Time onMgDisintegration Using 2% Lubripharm or Stearate 7:12 Mg Stearate as Lubricants - Mannogem EZ CarrierTM - 12EZkp Tablets kp. and Magnesium Stearate as Lubricants - Mannogem Carrier-12 Disintegration Disintegration Time (min)Time (min) Lower Disintegration Times re 1: harm or Mg Stearate as Lubricants - Mannogem EZ Carrier 8:24 6:00 Lubripharm 7:12 4:48 Mg Stearate 6:00 3:36 4:48 2:24 3:36 1:12 2:24 0:00 1:12 5 min. Blend 10 min. Blend 25 min. Blend 5 min. Blend 10 min. Blend 25 min. Blend 0:00 34000 Compression Force (N) Figure 4: Effect of Lubricant Level on Disintegration Using 2% Figure 4: and 3% SSF and Mg Stearate as Lubricants and Magnesium Stearate as MannogemTM Mannogem EZLubricants Carrier - 12 kp Tablets EZ Carrier - 12 kp re 2: Tablets made using Lubripharm arm or Mg Stearate as Lubricants - Mannogem EZ Carrier SSF are not highly sensitive to the levels of lubricant employed; the incorporation of 3.0% SSF 5 min. Blend ureLubripharm 2: harm or Mg Stearate Lubricants - Mannogem EZ Carrier to 2.0% Lubripharm SSF 10 min.as Blend Lubripharm SSF as compared 8:24 Figure 4: 14000 18000 22000 26000 30000 34000 Compression Force (N) 14000 18000 22000 26000 30000 Disintegration Disintegration Time (min)Time (min) Lubripharm SSF produced only a negligible increase in disintegration time, as shown in Lubripharm SSF 10 min. Blend Figure 4. Usage levels of Lubripharm SSF Mg Stearate 5 min. Blend are typically between 0.25–3.0% w/w Mg Stearate 10 min. Blend concentrations. Mg Stearate 5 min. Blend Mg Stearate 10 min. Blend Lubripharm SSF 5 min. Blend Lubripharm Mg Stearate and Magnesium Stearate as Lubricants MannogemTM EZ Carrier - 12 kp 7:12 34000 8:24 6:00 Mg Stearate 6:00 3:36 4:48 2:24 3:36 1:12 2:24 0:00 2.0% 3.0% 2.0% 3.0% 1:12 0:00 Compression Force (N) Lubripharm 7:12 4:48 Conclusions Lubripharm SSF provides for increased tablet robustness, reduced disintegration times, and decreased lubrication sensitivity as compared with magnesium stearate employed at equal levels. The use of Lubripharm SSF is indicated for disintegration- and dissolution-sensitive formulations such as orally disintegrating tablets and tablet formulations containing BCS Class II and Class IV APIs. Additionally, Lubripharm SSF is indicated for tablet formulations containing APIs which exhibit stability issues with magnesium stearate such as strongly acidic APIs (e.g. aspirin), iron salts, APIs containing ester groups (e.g. moexipril), and strongly basic APIs (e.g. erythromycin). Order No. SPI-EXC-LUB-0900-07201400 07-2014 | All rights reserved www.spipharma.com Your Partner for Formulating Success Americas SPI Pharma, Inc. Rockwood Office Park 503 Carr Rd., Suite 210 Wilmington, DE 19809 Europe/Middle East/ Africa SPI Pharma SAS Chemin du Vallon du Maire 13240 Septemes-Les Vallons France Asia/Pacific SPI Pharma, Inc – India Branch 21 B, Veerasandra Industrial Area Hosur Road, Bangalore – 560100 Karnataka, India Australia Distribution Company Anzchem 1 Braidwood Street Enfield NSW 2136 Australia T 302 576 8600 800 789 9755 Ext. 8600 F 302 576 8567 T 33 4 9196 3600 F 33 4 9196 3633 T 91 80 3027 0005 F 91 80 3027 0050 T 61 2 9475 2200 F 61 2 9475 2211 © SPI Pharma 2014. All trademarks are the property of SPI Pharma. The information contained in this document is proprietary to SPI Pharma and may not be used or disseminated inappropriately. The information and recommendations contained herein are to the best of SPI Pharma, Inc.’s knowledge reliable and accurate. Any recommendations are made without warranty, either implied or expressed, due to the variations in equipment, conditions, and methods which may be used in commercially processing the products. No warranties of any kind are made, express or implied, including those of merchantability and fitness for particular purpose, other than the products conform to current standard specifications. SPI Pharma, Inc. makes no warranty that the use of the products or formulations provided by SPI Pharma, Inc. will not infringe any trademark, trade name, copyright, patent or other rights held by any third party when used in customer’s application. 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