Tablets & Capsules


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capsules are faster and simpler to formulate than tablets and other dosage forms and can thus reach the market more quickly. Since they were first manufactured on a large scale in the USA in 1870, most hard capsules are made from gelatin, which has numerous desirable properties [2]. Other proper- ties of gelatin capsules, however, can pose a challenge dur- ing product development. The capsules can become brittle, for example, when stored at low relative humidity (RH), when filled with formulations containing hygroscopic sub- stances, or when exposed to a desiccant. Generally, the brittleness of empty capsules becomes an issue when RH falls below 40 percent. See Figure 2 [3]. This article discusses factors that influence brittleness and how to mitigate their effect so you can develop more robust capsules and capsule formulations. Brittleness Before studying capsule brittleness, we must define it. Brittleness of a material refers to the property of breaking without much permanent distortion. It is the opposite of elasticity, which describes a solid's ability to be stretched/deformed and then return to its original size [4]. Both phenomena can be observed when a solid—or in the case of gelatin, a polymer—is subjected to some force (energy). If the material is elastic, it accommodates the force through deformation, molecular movements (vibra- tion, rotation, and small translations), and heat. Brittle materials don't allow such modes of movements, and the impact energy is confined within a small localized area suf- ficient to directly rupture the material's bonds. Adding plasticizers—a common means of reducing the stiffness of polymers—works because it decreases the cohe- sive intermolecular forces along the polymer chain [5]. In hard gelatin capsules, water acts as the plasticizer. Therefore, a loss of moisture, perhaps due to low RH, causes the gelatin capsules to become brittle. Assessing the gelatin polymer Hard shell capsules are manufactured from a stock solu- tion of gelatin that also contains colorants and various process additives. To form capsules, stainless steel mold pins are dipped into the solution, coating them in film. After the film dries, the capsules are removed from the molds and cut to length. Next, the caps and bodies are assembled, and the complete capsules are sorted, printed, and packaged. The gelatin polymer is derived from the chemical degra- dation of collagen, and how it behaves depends on whether its macromolecules form a collagen-like helix or a coil con- figuration. In helical form, the gelatin is suitable for use at ordinary temperatures. In the coil form, which is more amorphous, the gelatin is a typical rigid-chain polymer and behaves as a brittle—and thus impractical—material due to the absence of water [6]. Not all gelatin types perform the same way, and you can learn about a gelatin's performance in terms of brittleness by analyzing two parameters: glass transition temperature and polymer crystallinity. Glass transition temperature. Abbreviated Tg, the glass transition temperature is the temperature at which the mechanical properties of a polymer change from those of an elastic material to those of a brittle one due to changes in chain mobility [7]. Polymer crystallinity. Gelatin coexists in two states: a crystalline, molecular aggregate state that follows a defined pattern and an amorphous state with no defined shape. As with other polymers, the crystalline form of gelatin is brittle. 16 January 2017 Tablets & Capsules Figure 1 Dosage forms of drug products approved by FDA and EMEA that contain NCEs, 2007 and 2015 Percentage of all dosage forms 50 40 30 20 10 0 2007 2015 Tablets Capsules Injection Others Source: FDA and EMEA [1] Figure 2 Percentage of capsules broken versus RH Broken capsule (%) 120 100 80 60 40 20 0 0 10 20 30 40 50 60 70 80 90 100 Relative humidity (%) Figure 3 Brittleness versus elasticity [4-6] Strain Stress Brittle materials (glass, chalk) Elastic materials (rubber) Elasticity Brittleness Ductile materials (soft metals) Source: Adapted from Kontny [3]

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