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Table 1 Hot-melt coating: A better approach An increasingly popular coating technique that is well- suited to a range of extended-release dosage formulations is hot-melt coating (HMC) [1]. Originally developed for food manufacturing, HMC offers a number of advantages over conventional solvent- based coating techniques. Since no solvents are involved, the process is rapid, typically taking less than 2 hours for a batch of 50 to 600 kilograms. Additionally, once the process parameters and excipients have been optimized, there are no curing or sintering effects, and the risk of unwanted side-processes occurring, such as agglomeration, is minimal. HMC works by coating API particles with a lipid excipient layer. The seed API particles are suspended in a fluid-bed coater (Figure 2), while the excipients are Extended-release formulations exhibit a number of properties different from immediate-release dosage forms. See Table 1. While these different characteristics create new opportunities for manufacturers, they present a num- ber of additional challenges. For example, all oral dosage forms, including extended-release formulations, should be easy to swallow and convenient to take. However, because extended-release dosage forms are often designed for once-daily dosing, the amount of active they need to carry can be double or triple what an immediate- release version requires. To demonstrate the factors that must be considered, we share below the approach taken to formulate an extended-release vitamin C product. We recently devel- oped the product for a market leader in the German food and dietary supplements industry. Controlling release using coatings Many extended-release formulations use coatings to control the rate of API dissolution and release. By care- fully selecting the coating agents, it's possible to control the dissolution profile of the API, facilitating immediate, extended, and even delayed release depending on the product's requirements. Traditional coating techniques apply a solution of the API and/or excipients to a seed particle using a fluid-bed process. While these are well-established methods, sol- vent-based coating techniques suffer from a number of drawbacks. One challenge centers on the need to dry the coated particles, which requires large amounts of time and heat energy, particularly when water is the solvent. As many coating approaches require the application of several lay- ers to achieve the desired extended-release effect, these steps can be time-consuming and resource-intensive. Additionally, many coating excipients do not dissolve in water, so organic solvents such as alcohols, ketone, and ethers must be used. While these solvents are more volatile than water and therefore dry faster, they are also more expensive, toxic, and flammable and must be used with care. 34 September 2017 Tablets & Capsules Figure 2 Hot-melt fluid-bed coater 4 3 2 1 4. The dust filter operates throughout the coating process, and the filter bags are cleared of dust by blowing air through the system. 1. The heated tank for the molten coating materials includes a stirrer and a system of heated tubing to prevent solidification of the molten materials before they reach the process chamber. 2. The air layer gliding process moves the particles into the spraying zone. 3. A heated nozzle sprays the liquid, using compressed air to create fine droplets for homogeneous coating. Immediate release Extended release Fast onset of action Slow onset of action Plasma concentration increases and decreases rapidly Plasma concentration is sustained for extended period Repeated dosing may be required (2 to 3 times daily) Once-daily dosing Frequent dosing may reduce compliance Once-daily dosing may improve compliance Less API per dosage unit Larger amount of API per dosage unit; well-suited for formulation as ODGs Potential for severe side effects because of high plasma concentration after ingestion Attenuation of side effects by avoiding brief, high plasma concentrations Crushing or chewing of dosage form unlikely to lead to high or toxic plasma concentrations Crushing or chewing of dosage form could destroy extended-release mechanism, leading to high or toxic plasma concentrations Characteristics of immediate- versus extended-release formulations