Issue link: https://www.e-digitaleditions.com/i/1218534
eye on excipients 40 March 2020 Tablets & Capsules Martin Junginger Gelita This installment of "Eye on Excipients" compares the pros and cons of using gel- atin versus the most common plant-based alternative, hydroxypropyl methylcel- lulose (HPMC), for hard capsule shells. Hard capsules are traditionally composed of pure gelatin and water and are available in a wide variety of shapes, sizes, and colors. Consumers find them easy to swallow, and indus- try prefers them because they protect sensitive drug formulations and offer a high level of API bioavailability. Hard capsules consist of a body section that contains the formulation and a cap section that fits securely over the body, reliably protecting the contents. They are often used for powdery or granulated formulations, but, increas- ingly, drug product manufacturers are also using hard capsules to deliver liq- uid and paste-like formulations. Capsule manufacturers consider many factors when designing and producing hard capsules. Consumer trends are often key considerations, and the industry seeks to accom- modate niche demands and cater to small market populations. Although gelatin-based hard capsules continue to dominate the hard-capsule market, use of plant-based hard capsules is growing quickly due to the demands of vegans and vegetarians. Marketing campaigns often lead consumers to believe that plant-based capsules are inherently better. For vegan or vegetarian consumers—who in principle and practice don't con- sume animal-based products—plant- based capsules are a suitable alter- native to gelatin-based ones. Some consumers, however, actively seek plant-based capsules based on a mis- conception that they offer better quality, contribute to better health, or use raw materials that are more sus- tainable. A closer look at the details reveals that, for many products, gela- tin capsules are likely a better choice. Sustainability Consumers with environmental concerns may believe plant-based capsules are more environmentally sustainable, but plant-based cap- sules don't necessarily support sus- tainable production. The most com- monly used, plant-derived alternative to gelatin for capsule manufacture is hydroxypropyl methylcellulose (HPMC). To process HPMC, the cellulose—generally derived from shredded trees—undergoes a rig- orous manufacturing process that involves chemical and synthetic, rather than natural, alteration. Cap- sule suppliers use volatile liquid pro- pylene oxide, considered to be a car- cinogen, and chloromethane gas to process HPMC and must ultimately remove and dispose of these highly reactive substances after production. While the resulting HPMC hard capsules are currently designated as vegan, plant-based, or vegetarian, a global debate is occurring about the naturalness of HPMC because it is a synthetic, chemically modified prod- uct. HPMC is also considered to be a food additive, designated as E464 in the Codex Alimentarius. Gelatin, on the other hand, is a nonallergenic food, not a food addi- tive. It is derived from the connective tissues of animals, namely cattle and hogs, a widely available by-product of the global meat industry. Capsule suppliers produce gelatin using an entirely natural and gentle method of hot water extraction, and its use in foods and capsules is essentially unre- stricted because it has enjoyed FDA generally recognized as safe (GRAS) status for decades. Ease of manufacturing Manufacturing HPMC-based cap- sules requires some modification to molding machines or to the formu- lation of the shell's materials. For instance, you must use heated pins and accurate temperature control in the whole production line. HPMC also requires the capsule manufacturer to use a higher temperature (70°C) for the polymer solution, compared to gelatin (which normally works in a temperature range of 45° to 50°C) and to carefully maintain the tem- perature of the capsule-forming pins after the dipping process to facilitate gelation until the film dries out [1]. While the higher thermostabil- ity of HPMC capsules can lead to advantages during filling processes and storing of the capsules, HPMC capsule shell walls are weaker than those of gelatin-made capsules, and removing the formed capsules from the pins, as well as subsequent han- dling and filling, is more difficult [2].