De-formulation/Reverse Engineering of Excipient

Excipients have a significant impact on the manufacturability and pharmaceutical performance of pharmaceutical formulations. Therefore, it is important to identify and control the Functionality-Related Characteristics (FRCs) of excipients in order to obtain safe, robust and stable products. However, in most cases, the limited information available on an excipient Certificate of Analysis (COA) has little effect on interpreting observed formulation properties or finding product-specific FRCs. Reverse engineering of excipients refers to the process of determining the specific identity and exact quantity of each component by breaking down a drug product formulation into separate components.

At BOC Sciences, the combination of our experts' knowledge of excipient properties and our specialized analytical laboratory facilities, methods and procedures, allows us to provide quantification of excipients and identification of individual excipients in drug formulations.

Figure 1. Schematic diagram of reverse-engineering approaches to drug discovery. (Ambesi, A.; Di Bernardo, D. 2006)

Why You Need De-formation Services?

• For specific biologically licensed bioequivalence (BE) strategies, Q1/Q2 (Q3) de-formulation may be required to produce a generic product that exactly matches a reference list drug
• Investigate a competitive or reference formulations
• Determine if patents are being infringed

Our Capabilities

• Our experience in excipient characterization and drug formulation de-formulation allows us to not only identify and quantify individual excipients in complex drug formulations, but also confirm the excipient grade, excipient quality, and sometimes even the excipient source of an ingredient
• BOC Sciences can provide high-quality reverse engineering services by introducing a range of complementary physicochemical methods and advanced sample preparation techniques covering many different excipients
• Our expert knows how to perform quantitation of excipients, including hydrocarbon based ingredients, polymers, modified cellulose, surfactants, emulsifiers and polyols

Quantification and Identification of Individual Excipients in a Pharmaceutical Formulation

For certain excipients, we have analyzed up to one hundred unique batches of different suppliers to expand our knowledge database. Our years of experience in excipient characterization have allowed us to not only identify and quantify individual excipients in drug products, but also to reveal and compare hidden excipient properties:

• The presence of potential reactive impurities or functional groups
• Degradation products and related substances
• Molecular weight distribution
• Degree of substitution
• Substituent distribution
• Monomer ratios and other characteristics

Techniques and Instruments Used in Pharmaceutical De-formation

• Fourier Transform Infrared Spectroscopy (FTIR) - All components in the excipients are able to be represented in the FTIR spectrum and then analyzed according to the BOC Sciences' database.
• Thermogravimetric Analyzer (TGA) - The sample is decomposed by a heating process, which is typically used to quantify the amount of inorganic residues and resins in the excipient.
• Gas Chromatography/Mass Spectrometry (GC/MS) - Gas chromatograph is capable of separating various components of a sample after decomposition so that they can be identified by mass spectrometry.
• Flame Ionization Detector (FID) - Using FID along with traditional methods of separating the solvents, followed by identification/quantification of the sample by GC/MS, provides further insight into the components in the excipients.
• Karl Fischer - Identify the water content in excipient samples.
• Scanning Electron Microscopy/Energy Dispersive X-Ray (SEM/EDXA) - Determine the type of elements present in the product sample using SEM/EDXA, which provides information about the inorganic excipients.
• X-ray Diffraction (XRD) - Useful for determining polycrystals in pharmaceutical excipients.
• Liquid Chromatography/Mass Spectrometry (LC/MS) - LC/MS is able to identify materials with higher molecular weights, therefore, LC/MS is often used to identify the ingredients used within the coating.
• High Performance Liquid Chromatography (HPLC) - HPLC helps to quantify the identified ingredients against purchased standards.
• Raman Spectroscopy - Raman spectroscopy provides a relatively high spatial resolution with the identification of components or mixtures of components in different sample regions. We can obtain information on the quantitative composition of the excipients including composition and particle size distribution from the obtained Raman maps.

Figure 2. Application of reverse engineering in the field of pharmaceutical tablets using Raman mapping. (Čapková, T.;et al.2022)