Assessment of Adsorption Behavior Between API and Excipient

Adsorption of pharmaceutical ingredients onto excipient materials affects the stability and efficiency of the drug through the loss of active pharmaceutical ingredients, resulting in reduced drug response and difficulty in controlling the concentration of the delivered drug. Excipients in formulations may adsorb to active ingredients and if these excipients are hydrophobic, dissolution rates and bioavailability may be retarded. Quantification of the amount of excipient adsorbed onto the surface of drug particles has demonstrated that only a very small amount of excipient is required to have a significant effect on the particle properties of the drug. For example, hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) have showed a large degree of adsorption and a significant effect on the physicochemical properties of the particles.

Classification of Adsorption Behavior

• Hydrogen-donating interactions

Direct drug-excipient interactions are most common when the interacting API and excipients are water-soluble and in liquid systems. For example, polyvinylpyrrolidone (PVP or povidone) can interact with API compounds containing hydrogen-donating functional groups. Hydrogen bond donor (HBD) sites can interact most efficiently with hydrogen bond acceptor (HBA) sites. Many excipients such as microcrystalline cellulose (MCC) and carboxymethyl cellulose (CMC) have multiple HBDs, and are able to form hydrogen bonds with HBAs in APIs.

• Charge interactions

Soluble and ionizable excipients can generate counter that interact with ionizable APIs, resulting in insoluble API-excipient products. This interaction is usually rapid and is evident in liquid systems.

Factors Impacting Adsorption Behavior

• Chemical properties of the excipients, and the quantities used
• Physicochemical properties of the drug such as concentration, spatial site resistance and lipophilicity

Figure 1. Energetics of adsorption on the surface of excipients. (Cazade, P. A.; et al. 2021)

Our Capabilities

BOC Sciences has introduced different methodologies and techniques to characterize the adsorption behavior between API and excipient since a comprehensive understanding of drug adsorption on excipient materials is essential for the design of more effective and safer drug delivery systems.

Differential Examining Calorimetry (DSC) & Fourier Change Infrared Spectrophotometry

We introduce DSC and FTIR technologies to measure the reactivity of drugs and excipients.

Monte Carlo (MC) and Molecular Dynamics (MD) Computer Simulations

At BOC Sciences, we characterize the range of adsorption energies and configurations encountered during adsorption of individual molecules of active pharmaceutical ingredients (APIs) on the surface of excipients using Monte Carlo and molecular dynamics simulations.

Scanning Electron Microscopy (SEM)

Our excipient teams employ SEM tool to characterize the API-excipient composite powder.

X-ray Photoelectron Spectroscopy (XPS)

We perform the XPS analysis of the surface components of the excipient-API to study that the excipients adsorb to specific surfaces of the API.

Molecular Modeling

We help our clients to understand the adsorption behavior at the macroscopic and microscopic levels by establishing a molecular modeling approach. The Gibbs free energy calculations are performed to investigate the strength of the interaction between the excipient surface and the drug.

High Performance Liquid Chromatography (HPLC)

Our experts perform HPLC experiments to separate and identify API particles restored on the surface of excipients.