Stearate, magnesium

Standards for dmg chemicals are pubUshed ia USP—NE. Dmg substances are chemicals that have therapeutic or diagnostic uses, whereas pharmaceutical iagredients provide preservative action, fiavoiing, or hilfillment of a function ia the formulation of dosage-form dmgs. Examples of dmg substances are acetaminophen [103-90-2] ampicillin [69-53-4] aspirin [50-78-2] powdered ipecac, riboflavin [83-88-5] staimous fluoride [7783-47-3] and thyroid. Examples of pharmaceutical iagredients are ethylparaben [120-47-8] lactose [63-42-3] magnesium stearate [557-04-0] sodium hydroxide [1310-73-2] starch [9005-25-8] and vanillin [121-33-5],... 

Ghdants are needed to faciUtate the flow of granulation from the hopper. Lubricants ensure the release of the compressed mass from the punch surfaces and the release/ejection of the tablet from the die. Combinations of siUcas, com starch, talc (qv), magnesium stearate, and high molecular weight poly(ethylene glycols) are used. Most lubricants are hydrophobic and may slow down disintegration and dmg dissolution. 

In addition to the formation of scale or corrosion of metal within boilers, auxiliary equipment is also susceptible to similar damage. Attempts to prevent scale formation within a boiler can lead to makeup line deposits if the treatment chemicals are improperly ehosen. Thus, the addition of normal phosphates to an unsoftened feed water ean eause a dangerous eondition by elogging the makeup line with preeipitated calcium phosphate. Deposits in the form of calcium or magnesium stearate deposits, otherwise known as "bathtub ring" can be readily seen, and are caused by the eombination of ealcium or magnesium with negative ions of soap stearates. 

Magnesium Stearate. See under Stearates which produces direct current and is manually... 

Calcium, and Magnesium Stearates and Calcium Resinate by Titration in a Nonaqueous Medium ,... 

Fig. 16 Effect of lubricant on dissolution of rate of salicylic acid contained in compressed tablets, x, 3% magnesium stearate , no lubricant 0> 3% sodium lauryl sulfate. (From Ref. 21.).

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],... 

The effect of raw material variability on tablet production [2,30,31] and suggestions for improving tableting quality of starting materials [21] has been the subject of several publications. Table 3, which lists the characteristics of different sources of magnesium stearate, clearly illustrates the variability of this material [32]. Phadke and Eichorst have also confirmed that significant differences can exist between different sources, and even different lots, of magnesium stearate... 

Given the fact that the effectiveness of magnesium stearate is due, in large part, to its large surface area, these variations should not be overlooked. In addition, studies assessing raw material variability emphasize the need for physical as well as chemical testing of raw materials to ensure uniformity of the final product. 

Table 3 Average Particle Data for Different Sources of Magnesium Stearate...

Fig. 12 Tensile strength of calcium sulfate tablets as a function of magnesium stearate concentration (solid fraction = 0.57). (From Ref. 29.)...

Lubricants such as magnesium stearate and stearic acid are also required. These facilitate the passage of the filling ring under the foot of the powder hopper... 

Fig. 17 Effect of powder bed height, piston height, and compression force on plug ejection force in an instrumented Zanasi LZ-64 automatic capsule-filling machine (pregelatinized starch lubricated with 0.005% magnesium stearate). Note that the first point of each curve is precompression. Piston height (mm) , 15 -jlf, 14 , 13 , 12. Powder bed height (mm) heavy line, 30 light line, 50. (From Ref. 51.)...

The most effective lubricants are the hydrophobic stearates, such as magnesium stearate, calcium stearate, and stearic acid. Magnesium stearate is the most widely used lubricant [117,118]. Lubricants proposed as being less hydrophobic such as hydrogenated vegetable oils, polyethylene glycols, and sodium stearyl fumarate are less effective in this application [118]. 

Interestingly, exceptions are possible. Stewart et al. [81] reported that the effect of magnesium stearate concentration on the dissolution of a model low-dose drug, riboflavin, from capsules was dependent in some manner on the type of filler. Soluble fillers exhibited the anticipated prolonged times with increasing lubricant levels. However, the trends with insoluble fillers were less predictable. In some cases insoluble fillers were only slightly affected by the concentration of magnesium stearate. For others, such as microcrystalline cellulose, there appeared to be an ideal intermediate concentration of lubricant at which the dissolution rate was maximized. 

Fig. 19 Effect of disintegrants on hydrochlorothiazide dissolution from hard gelatin capsules (filler, dicalcium phosphate lubricant, 1% magnesium stearate). (From Ref. 132.)...

Ong et al. [134] found that several hydrophilic anionic, non ionic, or cationic surfactants can alleviate the deleterious effect of magnesium stearate over-mixing on dissolution from capsules when added with the lubricant in a ratio as low as 1 5 (w/w). These successful surfactants were sodium A-lauroyl sarcosinate, sodium stearoyl-2-lactylate, sodium stearate, polox-amer 188, cetylpyridinium chloride, and sodium lauryl sulfate. The lipophilic surfactant glyceryl monostearate did not alleviate the magnesium stearate mixing effect. A reduction in thier particle size was shown to enhance effectiveness, particularly in the case of surfactants with low solubility and slow dissolution rate. 

The effectiveness of surfactants in overcoming the hydrophobic effect of magnesium stearate may not be a result solely of an increase in the wetting properties of the bulk phase. Compared to putting the surfactant in the dosage form, Botzolakis [71] and Wang and Chowhan [135] found that adding an equivalent amount of surfactant to the dissolution medium was not effective. The possible impact of the surfactant at... 

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