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Tablets & Capsules September 2017 41 because the capsules, after being filled with a liquid, must be sealed and dried. The design of capsules used for liq- uid encapsulation must also prevent or minimize the for- mation of bubbles when they are sealed so they do not become banana-shaped. Our company's Flofit capsules are an example of a capsule designed to avoid these prob- lems (page 39). Filling machines There is equipment to fill hard capsules with liquids at all scales, from R&D to production. Experimental batches can be filled manually using a hypodermic syringe. This enables formulators to conduct preliminary investigations into the integrity of the capsule shell, its compatibility with excipients, performance in in vitro and in vivo disso- lution tests, and its effect on pharmacokinetic properties. Benchtop and production machines operate semi- or fully automatically, and there are few challenges when scaling up for production because increasing the output only requires adding dosing pumps. Look for capsule filling machines that • Maintain the product at a constant temperature, up to 80°C, • Maintain a homogeneous suspension in the product hopper and filling block, • Fill accurate doses at volumes of 0.1 to 1.0 milliliter, • Eject the filled capsule body if the cap is missing, Figure 4 Cap of two-piece hard capsule Body of two-piece hard capsule Sealing band Liquid medicine Capsule suitable for liquid fills Filling liquids: Hard versus soft capsules Delivering liquid formulations, including those based on lipids, requires a container, typically either a hard cap- sule or soft capsule (softgel). Hard capsules have several advantages over softgels, including walls that are typi- cally one-third the thickness of softgel walls. As a result, hard capsules disintegrate faster. And unlike softgels, hard gelatin capsules do not require a plasticizer. Their two main ingredients are gelatin and water, while softgels require glycerin or sorbitol additions to soften the gelatin. Hard capsules are also stable in hot climates, while softgels become tacky and tend to clump. Hard capsules also allow less migration of the fill into the shell, and there is less diffusion of odors. And because hard capsules have fixed dimensions, they are easier to package, especially in blisters, than softgels, whose fill weight can vary throughout a batch, affecting the cap- sule's size and shape. And while hard capsules accept fills of thermo-stable substances as warm as 80°C, softgel fills are limited to about 35°C, although there is new technol- ogy that enables higher-temperature fills in some cases. The important point for formulators to consider when using a hydrophilic carrier is how compatible a hard cap- sule shell (no plasticizer) would be versus a softgel, which includes plasticizers. Hard capsules are typically made from gelatin or hydroxypropyl methylcellulose (HPMC). While it's beyond the scope of this article to detail the pros and cons of each, their main difference is moisture content. In HPMC capsules, it is lower and as a result, they are more elastic than their gelatin counterparts, which become brittle at low relative humidity. Furthermore, there are two types of HPMC capsules: Those that include a gelling agent and those that do not. Some studies suggest that the absence of gelling agent diminishes the shell's compatibility with liquid solvents, and some scientists have attributed the formation of splits and cracks imme- diately after banding to these HPMC shells [9-11]. Last, some patients and consumers favor HPMC capsules due to religious beliefs or dietary restrictions that preclude them from consuming a product made from animal parts. To accept liquid fills, hard capsules must have a geom- etry different from capsules that accept solids. That is AL RI P PTIONAL E C XC EX M on a a A y A Clean Ink Vi s e and v e on ail Cleaning S abl All odels! Mo ms d te st ys y ty sit ystems PRODUCTS L PRODUCTS. OUR YOUR F NTING OR Y M L easier o y 0 c ns f With vision inspection to en accuracy, single tablet rejec and output rates of up t up to 50 units per hour, identifying y products has never been easier . asier our 0,000 ction, e sur N U O F om tt.c .rwhartne A ed in the US actur anuf M ears Experienc Years Experienc 130 r 130 Ov Support and Servic l Support and Servic s OQ' / s and IQ T' AT' FA T' AT' SA s, FA Global er Y www NDED 1880 om tt.c o@rwhartne f in -969-9190 215 y! oda Toda U tact dwide. orl Worl tries 40 Coun r 40 Coun Ov Companies in f Companies in o eds reds y Hundr by rust Trust T ed by Hundr f er Con W A e c e vic s s T