Assessment of Drug-excipient Interactions in Solid Disperstion

A solid dispersion is defined as a dispersion of one or more active ingredients in an inert carrier. In the pharmaceutical industry, amorphous excipients with high glass transition temperature (T_g) are commonly employed in glass solutions of poorly soluble active pharmaceutical substances (APIs) to form solid dispersions. Amorphous drugs can be formulated into asmicroscale solid dispersions by a variety of manufacturing process such as spray-drying, freeze-drying or hot-melt extrusion in which the drug is usually stabilized by polymeric excipients. Common excipients with high glass transition temperatures include hydroxypropyl methylcellulose (HPMC) and poly(vinylpyrrolidone) (PVP). These polymeric stabilizers significantly reduce the molecular mobility of the dispersed drug and prevent recrystallization of the amorphous drug during storage, which is very beneficial when the drug is dissolved and supersaturated, increasing the absorption of the drug at the gastrointestinal barrier. BOC Sciences is ready to identify and evaluate the drug-excipient interactions since this type of interaction is necessary for a solid dispersion to stabilize.

Advantage of the Formation of Solid Dispersions

• Delay the crystallization of drug molecules
• Slow the diffusion of drug
• Increases the activation barrier for crystallization by forming the physical binding of drug molecules through hydrophobic, hydrogen bonding or other interaction sites on polymer chains

Figure 1. Classification of solid dispersions. (Shete, G.; et al. 2013)

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BOC Sciences has introduced several analytical techniques for determining complex formation in the solid disperstions.

Nuclear Magnetic Resonance Spectroscopy

There are specific drug-excipient interactions and phase behavior exist in amorphous solid dispersions of some APIs and drug polymer excipients such as Soluplus, polyvinylpyrrolidone vinyl acetate (PVPVA), hydroxypropyl methylcellulose succinate (HPMCAS), and hydroxypropyl methylcellulose phthalate (HPMCP). We have used solid-state NMR spectroscopy to study such drug-excipient interactions in amorphous solid dispersions.

• ¹³C and ¹⁵N solid-state NMR is employed to identify the changes in local structure and protonation (i.e., salt formation) of drug within the solid dispersions, which clearly indicates that whether ionic complexes form between drug and excipient in amorphous solid dispersions
• Thermal studies are carried out to assess the single glass transition (T_g) to identify the formation of the drug-excipient interactions in solid dispersion
• Additional services to study the dissolution and stability behavior of different drug-excipient systems.

Figure 2. Drug–Excipient Interactions in Biclotymol Amorphous Solid Dispersions. (Benjamin, S.; et al. 2018)

Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XPD) & Dielectric Relaxation Spectroscopy (DRS)

We chose three different solid-state characterization tools (DSC, XPD and DRS) to investigate the effect of low molecular weight excipients on the interactions between drug and excipients, molecular mobility and recrystallization tendency of amorphous active pharmaceutical ingredients. XRD is used to confirm the amorphous nature of the dispersion and DSC is applied to measure the glass transition temperature (T_g).

• Molecular dynamic behavior of solid dispersions near the glass transition temperature
• Quantum mechanical simulations to understand the interactions between drug and excipients
• Thermodynamics of amorphous solid dispersions to study drug-excipient stability