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Tablets & Capsules September 2020 9 Compactibility. Compactibility is also of concern because poorly compactible formulations require higher compression forces and increase the likelihood of bend- ing or buckling the sensitive microtip tooling that is used to compress minitablets. A common means of evaluating a formulation's compactibility is to conduct a Heckel plot. The Heckel equation is: ln(1/(1 - D) = KP + A) where D = relative density (density of powder/true density) K = measure of plasticity, with a higher K value indicating a harder tablet P = pressure applied A = die filling and particle rearrangement before deformation Minitablet benefits Due to their smaller size, minitablets are easier to swal- low than conventional tablets, which can be particularly helpful for pediatric and geriatric patients. Dysphagia, or difficulty swallowing, can reduce patient compliance, neg- atively impacting health outcomes and quality of life [1]. Minitablets have a higher surface-area-to-volume ratio than conventional tablets, so they can achieve faster dis- solution profiles. Also, minitablets can be beneficial for products containing high-potency drugs when used as multiple units within a capsule. They provide a more con- sistent dissolution profile than conventional tablets and allow the dissolution to be spread across a larger area of the digestive system [1]. Placing multiple minitablets into empty capsules can minimize the effects of tablet defects and weight vari- ations between tablets. For example, compare a single 350-milligram tablet to 35 minitablets—each 2.5 milli- meters in diameter and 10 milligrams in weight—filled into a #1 capsule. If the 350-milligram tablet is defective, increasing 50 percent in weight, then the patient will receive a 50 percent higher dosage. If one of the mini- tablets is defective, also increasing 50 percent in weight to 15 milligrams, then the capsule's overall weight is 355 milligrams, and the patient only receives a 1.4 percent higher dosage. Similarly, an individual surface defect on a minitablet, such as delamination resulting in faster dis- solution, has less impact on the overall dissolution profile of a collection of minitablets in a capsule than the same defect would have on a conventional tablet. While the manufacturing process is similar to that of conventional tablets, minitablet production requires some special considerations with respect to formulation charac- teristics and tablet design. Formulation characteristics Flowability and compactibility are critical characteris- tics when evaluating a formulation's feasibility for mini- tablet production. Flowability. Flowability is important because the for- mulation must flow into smaller die bores for minitablets than for conventional tablets, and the ratio between the fill depth and the die bore size is higher. Flowability is often measured indirectly using the Carr's index. A lower Carr's index value indicates bet- ter flowability, and you can expect good flow when the value is below 15 [2]. The formula is: C = 100 (1 - BD/TD) where C = the Carr's index BD = the formulation's bulk density TD = the formulation's tapped density Good microtip tooling design can mitigate some flow- ability issues for minitablet production. Since vacuum pressure aids in filling the die bores, optimizing the clear- ance between the punch tip and the die bore can improve vacuum pressure and help ensure adequate filling. Table 1 Minitablet cup profiles Profile Characteristics Flat Tooling is inexpensive and easy to measure and maintain. Flat face bevel edge (FFBE) Preferred profile if the tablets aren't to be film coated. Flat face radius edge Similar to FFBE but with a better punch force rating. Whisper face (lozenge) Provides a greater surface area compared to FFBE. Standard convex Can cause pinching between the take-off plate and the die table during tablet ejection. Compound radii Generally isn't helpful for minitablets because it doesn't significantly reduce tablet friability but does adversely affect tooling strength. Modified ball Seldom used due to low tooling strength, the occurrence of capping, and poor ejection.