Issue link: https://www.e-digitaleditions.com/i/1163217
38 September 2019 Tablets & Capsules capable of precisely blending cohesive or static-sensitive active ingredients. Examples are high-energy horizontal blenders, bin blenders, and cube blenders. Component blending Because each formulation contains different compo- nents and a unique ratio of particle sizes and shapes, some formulations will blend and lubricate much faster than others in the same blender. The unique end point of component blending is well defined in the FDA's SUPAC IR [2] and "Uniformity of Dosage Units" [3] guidance documents. Blend studies determine the proper endpoint for content but offer no real help in determining when the lubricant is properly distributed. Lubricant blending Once you have documented what kind of mixing behavior you have, you can determine the optimal lubri- cant mixing time. There is no magic formula. Also, the idea that most or all of the particles in a blend must be coated with lubricant for successful tablet compression is a myth. This would insulate the particles and prevent them from bonding to each other during tablet compres- sion, as shown in Figure 2. Die lubrication is accom- ties increase above that value (through a change in the rotation rate or fill level, for example), a different mixing pattern emerges, which can result in a different blending outcome. This effect increases the further the fill level strays from the target unless you alter the corresponding blending and lubrication times. Blending action All tumble blenders (also called gravity blenders) oper- ate primarily on the principles of diffusion blending (up and down, around and around) and axial blending (side to side). Under the FDA's scale-up and post-approval changes (SUPAC) guidance [1], eight subclasses of dry powder blenders are currently in use in pharmaceutical and nutraceutical manufacturing. The most common are listed in Table 1. Notice that these subclasses use varying ratios of diffu- sion versus axial blending. In addition, for twin-shell and double-cone blenders, the ratio of diffusion versus axial blending varies between first- and second-generation models, as shown in Figure 1. Some classes of blenders have less-than-optimal ratios between diffusion and axial blending and may not be Figure 1 First- and second-generation twin-shell and double-cone blenders a. First-generation twin-shell d. Second-generation double-cone c. First-generation double-cone b. Second-generation twin-shell Figure 2 Effect of particle lubrication in the die b. Properly lubricated formulation F U F L F D F R a. Over-lubricated formulation Lower punch Die Upper punch F U F L F D F R