Evaluation of strain-induced hydrophobicity of pharmaceutical blends and its effect on drug release rate under multiple compression conditions

Abstract

Objective: The purpose of this study was to investigate the effect of mechanical shear on hydrophobicity of pharmaceutical powder blends as a function of composition and particle size, and to determine the impact on drug release from tablets.

Methods: Four powder formulations were subjected to three different shear strain conditions (40 rev, 160 rev, and 640 rev) in a controlled shear environment operating at a shear rate of 80 rpm. A total of 12 blends were tested for hydrophobicity. Subsequently, sheared blends were compressed into tablets at 8 kN and 12 kN in a rotary tablet press. During tablet compression, powder samples were collected after the feed frame and their hydrophobicity was again measured.

Results: Results indicated that increase in shear strain could significantly increase hydrophobicity, predominantly as an interacting function of blend composition. Blends with both colloidal silica and magnesium stearate (MgSt) were found to show higher hydrophobicity with shear than other blends. Additional shear applied by the tablet press feed frame was found to change the powder hydrophobicity only in the absence of MgSt.

Conclusions: Studies showed that the drug release rates dropped with shear more for the blends with both colloidal silica and MgSt than the other blends. Furthermore, the rate of drug release dropped with a decrease in particle size of the main excipient. Surprisingly, the relationship between the relative increase in hydrophobicity and a corresponding drop in the drug release rate was not found when either MgSt or colloidal silica was mixed alone in the blends.

Figure 1

Apparatus for measuring hydrophobicity, which was measured from the slope of the squared mass versus time.

Figure 2

Effect of shear on hydrophobicity. Hydrophobicity increased with shear strain. The effect was dominant in the presence of lubricant and colloidal silica. With increase in strain, Cab-O-Sil alone did not alter the hydrophobicity. However, shearing the powders with MgSt alone and in combination with Cab-O-Sil increased the hydrophobicity.

Figure 3

Effect of feed frame on powder hydrophobicity. Although a slight decrease in hydrophobicity was found at low shear strain, feed frame was found to be ineffective in altering the hydrophobic behavior of powder.

Figure 4

Effect of shear strain on the drug release. Drug release slowed down at highshear conditions in the presence of Cab-O-Sil.

Figure 5

Effect of mixing talc in the blends on the dissolution profiles of tablets. Addition of talc did not change the dissolution behavior for two sets of blends shown in (a) and (b).

Figure 6

Effect of compression force on the dissolution of API. Higher compressive force slowed down the drug release only at the high-shear strain conditions.

Figure 7

Effect of shear strain and composition on dissolution of tablets. Drug release slowed down only at high-shear strain conditions (160 rev and 640 rev) in the presence of Cab-O-Sil. At the same time, addition of talc to the blends did not show any change in dissolution rates of the API in the tablets.

Figure 8

Effect of particle size on the dissolution. Although drug release slowed down with shear for both the blends, the release was slower for the tablets prepared with smaller particle size of excipient.