Overcoming Challenges to Deliver Fixed Dose Combination (FDC) Drug Products

Sponsored by Cambrex

June 2, 2020

With Cambrex’s experience in combining two or more active pharmaceutical ingredients (APIs) into Fixed Dose Combination drugs (FDCs), we are the CDMO that’s expertly positioned to partner with you. Discover the benefits and challenges as we review two unique FDC product case studies.

Drug product development holds great responsibility and requires the know-how to overcome challenges along the way. Manufacturers must identify safe, efficacious molecules and formulate them properly to protect patients. And all successful drug products require meeting global regulatory standards for the life of the product.

Cambrex is a contract development and manufacturing (CDMO) company with extensive drug product expertise. The team can support many different formulation types, including fixed dose combination (FDC) drug products, which combine two or more active pharmaceutical ingredients (APIs) into a single FDC product.

FDC product considerations

FDC drug products offer a multitude of benefits, including improving convenience and patient compliance, reducing manufacturing costs, repurposing proven compounds, or even extending a product patent life. However, when multiple APIs are combined, drug-to-drug interactions at the targeted dose level may impact safety and limit formulation potential. Compatibility studies are necessary to evaluate drug-drug and excipient interaction to ensure a stable formulation. 

The posology and ratio of API strengths in the FDC drug product must be balanced and is particularly critical when administered APIs have a cooperative therapeutic treatment. The target dissolution release profile of each API from individual dosage forms must be studied and applied to overcome any formulation or regulatory challenges.

Additionally, the patient population matters because not all patients are the same. Standard adult formulations will not always work for pediatric and geriatric patients based on swallowing or dosing ability, taste preferences, and the release of the drug. Accommodations must be made to ensure that the end user is treated safely and does not risk under- or over-dosing through the FDC product. And, not to be overlooked, taste masking is important to consider with every dosage form as it can impact patient compliance.

Analyzing FDC drug formulations 

There are a wide variety of oral solid dosage forms on the market. The following are most popular:

  • Tablets
  • Capsules
  • Mini tablets (within or without capsules)
  • Multi-particulates (formulated into capsule or tablet formats)
  • Powders for oral suspension

Analytical methods must be developed and validated for every FDC product. When there are multiple APIs with various strengths in the finished dosage form, characterization becomes paramount. This helps to find the right final FDC solid dose format and ensure the proper delivery of each API in the product.

Today, analytical methods are more advanced and rapid with options including ultra-high-pressure liquid chromatography (UPLC). Multiple API assays can be combined for the detection and quantification of impurities in one finished FDC product. This can be scaled to the individual project to save a great deal of cost and time for the customers. Additionally, working to address and overcome sensitivity and solubility issues by developing a single dissolution method rapidly advances the FDC development program.

A CDMO partner, invested in your success

An experienced CDMO acts as a partner to drug manufacturers, co-developing solutions that bring drug products to market on time with innovation, quality, and transparency as cornerstones of the relationship. 

Cambrex sets itself apart from other CDMOs with decades of process experience, and continued investment in technology and capabilities. The company features a broad range of multi-particulate technology for controlled-release formulations, and specializes in dry and wet granulation, roller compaction, extrusion/spheronization, ion exchange technology, and hot melt extrusion manufacturing technologies to enhance drug substance solubility and bioavailability. The team has knowledge of the latest regulatory guidance and hands-on experience working closely with regulatory agencies from pre-clinical development through to product approval and commercialization. Cambrex never stops working to be the right CDMO partner for the life of your drug products.

Richard Shook – Director, Drug Product Technical Services and Business Integration, Cambrex

For further information about Cambrex’s Drug Product services click here