Issue link: http://www.e-digitaleditions.com/i/883179
32D October 2017 Tablets & Capsules opening in the stomach's acidic environment but release once the pH exceeds 6.8 at or near the entrance of the intestines. Low-moisture HPMC capsules also shield ingredients from moisture that may permeate packaging. An enteric coating can be applied to softgels to achieve a similar release profile. However, the addition of a coating requires a second manufacturing process and may be unappealing to clean-label consumers. 6. What are some liquid formulation solutions for solid or semi-solid ingredients? Does your formula have a large amount of solids? Can they be suspended in a liquid or must they be solubilized for better absorption? For some ingredients, microniza- tion may improve solubility and absorption. For example, when L-arginine is micronized and solubilized, you can formulate it as a free-flowing liquid at a higher concentra- tion per dose. Encapsulating this fill in a hard capsule in a nitrogen-flushed environment has also been shown to offer superior stability compared to other forms of L-argi- nine. Micronization can also improve the emulsion char- acteristics of water-insoluble ingredients and even help create a self-emulsifying formulation. CoQ10 is available in softgels, powders, and efferves- cent tablets. However, a clinical study showed that when this coenzyme is solubilized in a lipid emulsifier and deliv- ered in a nitrogen-flushed and fused LFHC, it had 30 per- cent better bioavailability than the other dosage forms [7]. 7. Which polymer is best for your ingredients? The compatibility of the capsule polymer and ingredi- ents is key to maintaining a product's integrity and efficacy. If your ingredient is sensitive to moisture, light, and/or oxy- gen, the correct polymer can make all the difference. While softgels have been widely used for liquids, they provide a less effective barrier. A typical softgel contains about 16 to 20 percent moisture, which ingredients can absorb and thus degrade the shell or fill. A softgel's plasti- cizers can create micro-channels, which allow oxygen to enter, odors and tastes to seep out, and ingredients to migrate into the shell. Antioxidants may help block smells in the bottle, but some people don't want added ingredients and some can't tolerate flavorings. Again, hard capsules contain less moisture than soft- gels. More specifically, fish, bovine, and porcine gelatin capsules contain 13 percent moisture, while HPMC cap- sules contain 3 to 6 percent. All types of hard capsules are more suitable than softgels for hygroscopic ingredients such as probiotics, enzymes, herbal extracts, choline chlo- ride, L-arginine, L-carnitine, and betaine. The absence of plasticizers in hard capsules eliminates micro-channels. This makes hard capsules a better fit for aro- matic nutritional oils and marine oils than softgels because they effectively block smells and mitigate oxidation. Pullulan, which is naturally fermented from tapioca, offers the best oxygen barrier of all—even better than gelatin and HPMC—without the use of additives. Capsules made of pullulan are also vegetarian; starch-, gluten-, and preservative-free; and non-GMO Project verified. 8. How can you alter ingredients' release profile? If you are delivering a combination of ingredients or an ingredient requiring delayed and/or targeted release, you should consider capsule-in-capsule technology. A vegetar- ian capsule-in-capsule is especially helpful for delivering moisture-sensitive prebiotic-probiotic supplements. The outer capsule that contains the prebiotic dissolves first so it can prepare the environment for the probiotic in the inner capsule, which dissolves later to reach the intestinal tract. Capsule-in-capsule technology can also combine incompatible ingredients or ingredients that would re- separate after mixing. Given that oil and water don't mix, filling an inner capsule of krill oil into an outer capsule of water-based L-carnitine allows you to overcome this issue. Isolating these two ingredients into separate compart- ments also improves stability and efficacy and removes the burden of taking two dosage forms for brain health. This technology can also be used for extended-release formulas. Melatonin is a good example. Solubilized in a water-based system, the melatonin liquid in the outer capsule is available for immediate release. Melatonin beads in the inner capsule dissolve later at different inter- vals due to the varied thickness of the coatings, thus extending the effects of this sleep-aid. Beads suspended in an LFHC can also offer delayed- or extended-release profiles. For example, caffeine beads can be suspended in a caffeine liquid. When ingested, the outer capsule dissolves and releases the liquid immediately, then the beads dissolve slowly over time. 9. What are key areas to explore when vetting a CDMO? Your brand representative should review the complete capabilities, processes, and controls that a CDMO can provide. Aspects to examine include how long the manu- facturer has been in the industry, the condition of its facili- ties, the equipment being used (especially pertaining to liq- uid filling), and the training records of the staff involved. In addition, the manufacturer should inform you of the certifications it holds for its products and services. This can include vegan, kosher, halal, TGA, NSS, ISO, UL, Non-GMO Project, and Vegetarian Society certifications. If the facility has been audited by the FDA, what were the results? As the brand holder, you are responsible for the safety of your products. That means you need to know the processes in place for identifying ingredients, microbial and heavy metal contamination, and residual solvents according to the standards. With the GMP regulations under 21 CFR 111 and now the most recent Food Safety Modernization Act regulations—which require companies of all sizes to incor- porate risk management as well as cGMPs—it is essential that you meet with your CDMO and review records. To ensure that GMPs are followed, review batch records to verify that tests were completed and recorded properly for all materials. You could also attend a production run to underscore the importance you place on quality products.