Issue link: https://www.e-digitaleditions.com/i/947832
Tablets & Capsules March 2018 39 A dose differential between the APIs also poses formulation and processing challenges. For instance, if the dose of one API is low and the dose of the other API is high, each API should be processed individually and combined at the final stage as a bilayer, tablet-in-tablet, or capsule-in-capsule form. An FDC with three APIs, where API A and API B are low-dose and API C is high-dose with an extended- release profile, presents many formulation challenges. In such a case, you can formulate API A and API B using high-shear granulation and process the high-dose API C by extrusion spheronization technology. Then you can apply an extended-release polymer coating only to the API C spheres and compress the blended API A and API B granules and the coated API C spheres into a bilayer tablet. Other challenges associated with FDCs include: • Drugs with differing pharmacokinetics create a problem of administration frequency when combined into an FDC. • FDCs can increase the chances of adverse drug effects and drug interactions compared to single-API dosage forms. • Determining the cause of an adverse drug reaction can be difficult because the FDC contains more than one API. • Pharmacists and physicians may overlook the dosage limit of certain APIs in FDCs. formulation requirements, then the particle size distribution of all the APIs and excipients should be uniform to prevent segregation and provide good flow and content uniformity. M u l t i p a r t i c u l a t e / m i n i - t a b l e t d o s a g e f o r m s . Multiparticulate or mini-tablet dosage forms are also useful for combining incompatible APIs or excipients or when a formulation requires that the APIs have different r e l e a s e p r o f i l e s . T h e m o s t c o m m o n l y u s e d multiparticulate oral solid dosage form is pelleted and/or powdered material compressed into a tablet or encapsulated into a capsule. A more recent manufacturing trend is to create various mini-tablets with diameters smaller than 3 millimeters (Photo 2), which can then be encapsulated into capsules (Photo 3) depending on the formulation's requirements. One of the most common technologies used to create pellets for a multiparticulate FDC is extrusion- spheronization, where the formulation is granulated to prepare a wet mass, which is extruded into cylindrically shaped extrudates. The extrudates are then broken into smaller particles and rounded off to create spheres, which are then dried. Extrusion-spheronization allows for high drug loading and can create pellets with a narrow particle size distribution. The pellets are also durable, making them suitable for film coating for pulsatile drug delivery and combining immediate-release pellets with controlled- release pellets of the same or a different drug. Adjusting the fill weight of the pellets into the capsule allows for dosing flexibility. Another way of producing a multiparticulate system is by preparing the drug in a solution or suspension and coating it onto readily available sugar pellets. You can then add an additional controlled-release coating to the pellets if required or combine immediate- and extended- release pellets. Development challenges and limitations Because FDCs contain more than one API, they're more challenging to develop than single-entity drug products. The challenges are largely related to formulation, dose-ranging, drug-drug interactions, and manufacturing processes. FDC development is also challenging when the APIs' durations of action differ significantly. In some cases, drug interaction at the level of pharmacokinetics, efficacy, or safety may limit formulation potential. In other cases, the API dosage becomes too large to administer as a single form. Also, the potential for BE failure is a factor, particularly when the dissolution profiles of the APIs to be combined differ. FDC use may also be limited where the component therapies require dose titration or various dose adjustment patterns because it's not possible to alter the dosage of one drug in the FDC without altering the dosage of the other drug or drugs [7]. INDUSTRIAL DUCTING HOSE by Kuriyama Our new ducting hose catalog features available ducting hose product options that Kuriyama has to offer, such as: • New Urevent ™ Clear • New Urevent ™ Black • New Urevent ™ HD • New Vinylduct ™ Clear • Tigerflex ™ PVC and poly- urethane ducting hoses • Hose Tec ® Metal hose options • Other ducting products made with polypro- pylene, silicone and neoprene materials. 360 E. State Parkway | Schaumburg, IL 60173 (847) 755-0360 | Fax: (847) 885-0996 sales@kuriyama.com | www.kuriyama.com