The Development of Innovative Dosage Forms of the Fixed-Dose Combination of Active Pharmaceutical Ingredients

Abstract

The development of innovative forms of combination drugs is closely related to the invention of the multilayer tablet press, polymers for pharmaceutical applications, the hot-melt extrusion process, and 3D printing in the pharmaceutical industry. However, combining multiple drugs within the same dosage form can bring many physicochemical and pharmacodynamic interactions. More and more new forms of fixed-dose combinations (FDCs) have been developed due to work to overcome the incompatibility of active substances or to obtain different drug release profiles in the same dosage form. This review provides discussions of the application of various innovation formulation technologies of FDC drugs such as bilayer system, multilayer tablet, active film coating, hot-melt extrusion, and 3D printing, taking into account the characteristics of the key ingredients in the FDC formulation and presenting technological problems and challenges related to the development of combination drugs. Moreover, the article summarizes the range of dosage forms that have been made using these technologies over the past 30 years.

Comparative pharmacokinetics between two tablets of tramadol 37.5 mg/acetaminophen 325 mg and one tablet of tramadol 75 mg/acetaminophen 650 mg for extended-release fixed-dose combination

“…FDC formulation has been developed in various therapeutic areas with many advantages [ 18 19 ]: co-administration of 2 or more molecules with complimentary mechanisms of action or synergistic effects in one tablet; improvement to patient compliance with reduction in pill burden. However, it may have limitations such as less flexible dose adjustment and difficulty in identifying ingredients causing the adverse drug reactions [ 18 19 ]. Meanwhile, the FDC formulation of tramadol and acetaminophen is recommended to use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [ 11 ].…”

Recent Advancements in Metallic Drug-Eluting Implants

“…The substrate was porous Ti alloy that printed in three dimensions (3D) and loaded with organic temperature-sensitive poloxamer 407 hydrogel, as seen in Figure 5 [ 88 ]. Since 3D printing was introduced in the field of biotechnology, it has shown excellent ability in the biomedical engineering and pharmaceutical field because of its high adaptability in utilizing various materials, its ability to develop intricate engineering parts, as well as its high efficiency in terms of time and cost [ 89 , 90 ]. In high concentrations or following burst release of BPs, osteoclasts as well as osteoblasts can undergo apoptosis.…”

Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery

“…[40] FDCs can also unlock previously inaccessible drug product profiles, with different drug release profiles enabling therapeutic synergies. However, difficulties manufacturing FDCs have limited their clinical translation, [41][42][43] particularly for APIs that are compatible with different excipients. [43,44] Researchers have recently used coreshell structures as a drug product geometry that can structure drugs in distinct polymeric layers, control the release of multiple payloads, and engineer stimuli-responsive functionality.…”