Lubricants in Pharmaceutical Solid Dosage Forms
Abstract
:1. Introduction
2. Fundamentals of Lubrication
2.1. Friction
2.2. Friction and Adhesion
2.3. Lubrication
2.3.1. Lubrication in Pharmaceutical Processes
2.3.1.1. Wall Friction
2.3.1.2. Powder Flow
3. Common Lubricants Used in Drug Development
3.1. Metallic Salts of Fatty Acids
3.2. Fatty Acids
Fatty acid | Formula | Molecular weight | Melting point (°C) | Boiling point at 16 mm (°C) |
---|---|---|---|---|
Stearic | CH3(CH2)16COOH | 284 | 69.6 | 240 |
Palmitic | CH3(CH2)14COOH | 256 | 62.9 | 222 |
Myristic | CH3(CH2)12COOH | 228 | 54.4 | 202 |
Surfaces | Lubricant | Coefficient of friction at 20 °C | Breakdown temperature (°C) |
---|---|---|---|
Copper | 1% stearic acid Smear copper stearate | 0.08, smooth 0.08 | 90 94 |
Platinum & cadmium | 1% stearic acid Cadmium stearate | 0.05 0.04 | 130 140 |
Platinum & steel | Smear sodium stearate | 0.1 | 280 |
3.3. Fatty Acid Esters
3.4. Inorganic Materials and Polymers
4. Magnesium Stearate
4.1. Effect of Pseudo-Polymorph [20,21]
Formula | Magnesium stearate ratio | Pre-Compression force | Main compression force | Ejection force | Porosity | Overall ranking |
---|---|---|---|---|---|---|
1 | A50:M50 | F | F | P | P | 12th |
2 | A25:M75 | P | G | P | P | 11th |
3 | A75:M25 | P | G | F | F | 5th |
4 | D50:A50 | P | G | G | G | 5th |
5 | D75:A25 | F | G | G | G | 3rd |
6 | D25:A75 | F | P | G | G | 4th |
7 | D50:M50 | F | P | P | F | 8th |
8 | D75:M25 | F | F | F | P | 8th |
9 | D25:M75 | F | F | F | P | 8th |
10 | Anhydrous | G | F | G | F | 2nd |
11 | Monohydrate | F | P | P | P | 7th |
12 | Dihydrate | G | F | G | F | 1st |
4.2. Effect of Powder Properties on Lubrication
4.3. Effect on the Mechanical Properties of Compressed Products [33,34,35]
4.4. Online Monitoring of Magnesium Stearate in Blending
5. Chemical Stability and Compatibility
5.1. Potential Interactions with Impurities (MgO)
5.2. Hydrolytic Degradation at Basic pH
5.3. Oxidation
5.4. Metal Ion-Mediated Degradation
5.5. Reaction with Amines
5.6. Other Interactions between Magnesium Stearate and Drugs
5.7. Stearic Acid
5.8. Sodium Stearyl Fumarate
6. Considerations for Selecting a Lubricant
Water soluble lubricant | Amount in formulation (%) | Water insoluble lubricant | Amount in formulation (%) |
---|---|---|---|
Boric acid | 1 | Metal (Mg, Ca, Na) stearate | 0.25–2 |
Carbowax (PEG) 4000/6000 | 1–5 | Stearic acid | 0.25–2 |
Sodium oleate | 5 | Sterotex | 0.25–1 |
Sodium benzoate | 5 | Talc | 1–5 |
Sodium acetate | 5 | Waxes | 1–5 |
Sodium lauryl sulfate | 1–5 | Stear-O-Wet | 1–5 |
Mg-Lauryl sulfate | 1–2 | Glyceryl behenate (Compritol 888) | 0.5–3 |
7. Conclusions
Acknowledgments
Conflicts of Interest
References
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Li, J.; Wu, Y. Lubricants in Pharmaceutical Solid Dosage Forms. Lubricants 2014, 2, 21-43. https://doi.org/10.3390/lubricants2010021
Li J, Wu Y. Lubricants in Pharmaceutical Solid Dosage Forms. Lubricants. 2014; 2(1):21-43. https://doi.org/10.3390/lubricants2010021
Chicago/Turabian StyleLi, Jinjiang, and Yongmei Wu. 2014. "Lubricants in Pharmaceutical Solid Dosage Forms" Lubricants 2, no. 1: 21-43. https://doi.org/10.3390/lubricants2010021