Crystalline Behavior Research of Excipients

Physical instability is a major challenge for the use of neat amorphous active pharmaceutical ingredients in tablets and capsules. The conversion of the amorphous form to the crystalline state during storage or drug dissolution constitutes a physical instability of amorphous drugs, and hinders the solubility advantages they offer. Therefore, in practical pharmaceutical applications, the application of polymeric, co-crystallized excipients is required to stabilize the neat amorphous drugs. Based on the interaction between drug and low molecular weight excipient molecules, excipients can effectively impede the molecular mobility. In general, excipients contain water and need to interact with it. The water associated with excipients can exist in various forms, which can be referred to as free water, bound water, structural water, and water of crystallization. The type of water will determine how it is involved in the interaction between the excipient and the API or other excipients. Free water is the form that is most often associated with excipient interactions, which will lead to the formation of crystalline excipients. During the formulation, excipients enhance aerosol dispersibility. In addition, the crystallinity of excipients in drugs is associated with changes in the particle morphology of active pharmaceutical ingredients (API), reduction in powder density and improvement in dispersibility. Compared to amorphous bulking agents, the presence of crystalline excipients also results in a lyophile with a low water content.

Figure 1. Combining crystalline and polymeric excipients in API solid dispersions. (Veith, H.; et al. 2020)

Crystalline Behavior Research Services

The crystallization of excipients can significantly affect the bioavailability of dosage forms, and BOC Sciences uses a variety of characterization tools and analytical methods to help our customers achieve improved drug performance and commercial viability.

Differential Scanning Calorimetry (DSC)

DSC is an analytical technique commonly used to detect and quantify the crystalline content of drugs, foods, polymers and many other materials. The heating process in a DSC experiment shows up as an endothermic peak, the temperature and area of the peak can be used to help identify, characterize and quantify the crystalline structure. At BOC Sciences, we perform DSC testing and analysis of pharmaceutical excipients and investigate the effects of crystalline structure on the properties of synthetic drugs.

X-Ray Diffraction (XRD)

X-ray diffraction measurements are developed based on the three-dimensional structure of a sample caused by the physical arrangement of atoms and molecules. Recently, XRD has been used to "fingerprint" specific solid forms of crystalline excipients in order to identify any changes in solid form throughout the product development and commercialization process. At BOC Sciences, X-ray diffraction (XRD analysis or XRPD analysis) is used specifically to determine the crystallinity of compounds.

Our Comprehensive Services:

• Distinguishing between amorphous and crystalline excipients
• Quantification of the percentage crystallinity of excipients
• Quantification and identification of polymorphic forms in the excipients
• Quantitative and qualitative analysis of crystalline chemical compounds present in the excipients

Figure 2. Effect of crystalline celluloses in structural engineering of composite oleogels. (Bhattarai, M.; et al. 2022)

Raman Spectroscopy

Raman spectroscopy has been used as an important research tool in different areas of the pharmaceutical industry, and it is increasingly being accepted as a powerful tool for pharmaceutical research and analysis. In general, the different applications of excipients can be distinguished as follows: diluents, binders, lubricants, dispersants, etc. Our Raman department investigates the Raman spectra of the most commonly used excipients in pharmaceutical formulations, and these spectra can be used as a reference to simplify the interpretation of the different Raman spectra during drug analysis. Moreover, we recommend our Raman spectroscopy analysis service for the study of crystallinity of microcrystalline cellulose (MCC).