Excipient magnesium stearate

It is important for the formulator of a new drug substance to know with which excipients he can work and with which he cannot. Some pharmaceutical incompatibilities are known to the formulator, e.g., magnesium stearate/aspirin, and glucose/amines [53],... 

Excipients Calcium carbonate, candeUUa wax, croscarmeUose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, microcrystaUine cellulose, polysorbate 80, simethicone emulsion... 

Excipients Croscarmellose sodium, edible inks, gelatin, lactose monohydrate, magnesium stearate, povidone, sodium lauryl sulfate, and titanium dioxide... 

Formuiation The formulation consists of excipients such as carnauba wax, crospovidone, hydroxylpropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, and other inactive ingredients. 

Presented together by the British, European, Japanese, and U S. Pharmacopeias, the first Interpharmacopeial Open Conference on Standards for Excipients was convened in Orlando, FL, from January 30-February 1, 1991 (Table 1). Attended by 165 participants, representation included 11 countries, 59 pharmaceutical or excipient manufacturers or suppliers, three regulatory agencies (FDA, EEC, and HPB), and seven pharmacopeias (the presenters and the French, Italian, and Spanish Pharmacopeias) [17]. In preparation for this conference, USP convened open meetings on Magnesium Stearate and Lactose attended by almost every major manufacturer from Europe and the United States. 

Experience gained by harmonizing the first of the excipients. Lactose and Magnesium Stearate showed that because so many parties are affected and many expert groups must be convened, forward, retrospective harmonization is intrinsically a lengthy process. 

One very common beneficial interaction involving an excipient is the interaction between magnesium stearate and the metal of tablet punches and dies, or the equivalent parts on a powder encapsulation machine. Magnesium stearate is an example of a boundary lubricant. As such it has a polar head and a fatty acid tail. It is believed that the polar head of the magnesium stearate is oriented toward the die wall or tablet punch face. In these ways it is able to reduce the ejection force (the force required to eject the tablet from the die after compaction) and prevent sticking to the punch faces. The other boundary lubricants, e.g., calcium stearate and sodium stearyl fumarate, will also function in a similar manner. However, the so-called liquid film lubricants function in a very different manner (19). 

A tablet formulation is a complex system that contains the drug substance, usually a hydrophilic Lllersuch as lactose, a disintegrant such as cornstarch, a lubricant such as magnesium stearate, and maybe a Low-regulating excipient such as silicium dioxide (A sliilnfortunately, the quality... 

Figure 7.10 Chemical image analysis of six tablets composed of 80 mg of furosemide (API) mixed with 240mg of the excipient mix (99.7% Avicel PH 102 and 0.33% magnesium stearate). Tablets A-E were created in the laboratory using increasing blending time, tablet F is an example of a commercial product. These PLS score images of the tablets highlight the location of the API component (bright pixels), and show the gross blend-quality differences.

Amines are particularly prone to reaction with excipients and salt counterions, as shown in Figure 45 for tartaric acid. The potential for a reaction with magnesium stearate or stearic acid is particularly of concern with an API containing a primary amine. In the case of norfloxacin, formation of a stearoyl derivative was observed in tablets containing magnesium stearate after prolonged storage at 60°C (Fig. 46) (81). 

Ester formation with hydroxyl-containing APIs has been observed for acid salts (e.g., succinic acid, citric acid, formic acid, acetic acid, etc.) as well as excipients (e.g., stearic acid, magnesium stearate). See Figure 85 for an example of the reaction of a hydroxyl group with succinic acid (124). 

Today, there is more emphasis on quality of excipients. For example, some inherent quality variability may occur in the natural products magnesium stearate and sodium starch glycolate. What is the impact of the variability of these excipients on product quality attributes Also, excipient viscosity, molecular weight, and particle size relative to API particle size could be critical factors to some formulations. An optimal dissolution method can only be developed on the basis of knowledge of the dmg product. 

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