Lubricants disintegration time

Glyceryl palmitostearate is used in oral solid-dosage pharmaceutical formulations as a lubricant. Disintegration times increase and tablet strength decreases with increase in mixing time. 

The processes may be studied quantitatively by comparing the means and standard deviations of the two populations. The effect of final blend time on lubricant distribution was examined by comparing disintegration time statistics for the grouped data. None was noted. 

Lubricants such as magnesium stearate are not used as their aqueous insolubility leads to cloudy solutions and extended disintegration times. Spray-dried leucine and PEG are water-soluble alternatives [15,16]. Both artificial and natural sweeteners are used and an additional water-soluble flavoring agent may also be required. If a surfactant is added to enhance wetting and dissolution, the addition of an antifoaming agent may also be considered [17]. 

Disintegration time, crushing strength, and friability of tablets, produced from Cop-MC using magnesium stearate as a lubricant, were found to be independent of the particle size of the prepared granules (Fig. 2.46). 

FIGURE 2.46 Effect of the particle size of the coprocessed excipient of chitin-mannitol on tablet crushing strength, disintegration time, and friability prepared from this excipient. The tablets were 9 mm in diameter and 180 mg in weight. All samples were lubricated with 0.5% (w/w) magnesium stearate. 

Sodium stearyl fumarate has been used as an alternative for magnesium stearate. It has about the same lubricating effect, and causes similar tablet strength reduction and prolongation of disintegration time. ... 

Although the effectiveness of many disintegrants is affected by the presence of hydrophobic excipients such as lubricants, tbe disintegrant efficiency of sodium starch glycolate is unimpaired. Increasing the tablet compression pressure also appears to have no effect on disintegration time. ... 

Let us now identify the 2 levels (or states) of the factor as A and B. The factor or variable might be the choice of excipient, as in a previous example. Thus tablets may be formulated using 1% magnesium stearate (Fj = A) or another lubricant such as 2.5% hydrogenated castor oil (Fj = B). The disintegration time or other properties of the resulting tablets are then measured. 

Thus, P i,b/a describes the effect on the response of changing F, from state A to B. In our example, it is the increase of the tablet disintegration time resulting from the replacement of 1% magnesium stearate in the formulation by 2.5% hydrogenated castor oil. This method introduces a certain asymmetry between the 2 levels, which is perhaps not justified. Why choose one level, or one lubricant, as the reference state rather than another ... 

As an example, consider the percentage yield of a chemical reaction, the response y, measured when the factor "reaction temperature", F, can take one of the two levels 25°C and 40°C. The two experiments are represented in the plan below, and a further column has been added for the experimental results. This is a non-pharmaceutical example, but the reasoning would be identical for the case of tablet disintegration times resulting from the use of different lubricants. 

A Box Behnken experimental design was used to predict the effect of hydrophobicity, lubricant level and excipient brittleness on spironolactone dissolution, compact disintegration time and particle size. The ANOVA table for the cubic and quadratic models is shown in Table 6. However, the experimental data did not fit the surface models for drug dissolution (r = 0.5728). This is explained by the small variability of data for drug dissolution with lubricant levels and lubricant hydrophobicity. Even though all tablet batches contained a disintegrant, none of them was able to release 100% of spironolactone within 1 hour of study. This is explained by the hydrophobic nature of the drug which restricted dissolution. 

The lubricant level had no effect on the particle size and was not significant for the compact disintegration time. The predicted combination of factors that rendered the shortest disintegration time and a particle size between 98 and 210 pm was achieved with stearie acid at a 1.5% level in mixtures with lactose monohydrate rendering a disintegration time and particle size of 13 s and 104 pm, respectively. These values are closed to the ones obtained from the validation run (23 s and 98 pm, respectively). 

Two additional experimental designs were carried out to optimize the formulation and granulation process (water addition time, granulating time, and addition of binder—dry versus in-solution— binder level, disintegrant level, and lubricant level). There was a trend toward improved compaction profiles and reduced friability with increased granulation time. It was also observed that the lubricant and disintegrant levels affected the friability of the tablets. The effect of the lubricant level on tablet friability is shown in Figure 20. The final formulation and process are summarized in Table 5. 

Run Binder (%) Lubricant (%) Disinte-grant (%) Glidant (%) Water (%) Compression force (kN) Disintegration Hardness (Kp) time (secs) Friability (%) ... 

Time (min) Target Formulation Additional Lubricant Diluent Substitution Disintegrant Removed Additional Binder High Tablet Hardness... 

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