Assessment of Degree of Substitution (DS) of Derivatized Celluloses

The degree of substitution of a polymer is the (average) number of substituents attached to each monomer unit. The DS is defined as the average number of substituted hydroxyl groups per glucose unit, and the term is mainly used in cellulose chemistry. Cellulose is the most abundant natural polymer from renewable sources. Products of cellulose ethers or cellulose derivatives are widely employed as pharmaceutical excipient. DS of MC play critical roles in its physicochemical properties, such as water solubility, thermal stability, thickening, and gel- and film-forming properties. When some polymeric materials are used as excipients in solid form, they may have poor water resistance and low mechanical strength. Several chemical modifications have been carried out to improve these disadvantages. Chemical modifications involve the substitution of functional groups in the polymeric excipients’ structure, including esterification and etherification, and the lengthening of the molecular chains through the formation of crosslinks and encapsulation. Depending on the DS, these modifications significantly alter several properties of the excipients, such as homogeneous film formation, increased tensile strength, improved thermal stability and sustained release of active pharmaceutical ingredients. Therefore, accurate determination of DS is very important because DS is the main measure that determines the properties of excipients.

Figure 1. The effect of the degree of substitution on the solubility of cellulose acetoacetates in water. (Wu, W.; et al. 2020)

Our Services of Assessment of DS

The DS of the cellulose backbone has a large impact on the hydrophilic/hydrophobic character of the cellulose derivatives and its functionality in pharmaceutical applications. It is therefore important to control and characterize this critical property. BOC Sciences can provide accurate information about the DS by offering fast and flexible hands-on characterization services for cellulose derivatives.

Nuclear Magnetic Resonance (NMR) Spectroscopy

At BOC Sciences, calculation of the DS of cellulose acetate samples is achieved by nuclear magnetic resonance. The DS of the cellulose derivatives is analyzed using NMR spectroscopy by comparing the carbonyl carbon integral of the cellulose derivatives with the cellulose C1 signal integral.

• First, the cellulose sample is dissolved in a suitable solvent
• Then, the DS is measured by integration method of ¹H NMR signals: The quantification of the number of acetyl groups present in the sample is determined by comparing the area of methyl group signals and the area of ring proton signals.

Figure 2. Characterization of the DS pattern of cellulose derivatives using carbohydrate-binding modules. (Schantz, L. V.; et al. 2014)

Fourier Transform Infrared (FTIR)

FTIR is used to determine the DS of cellulose derivatives. The introduction of acetyl groups, carboxymethyl groups and carbonyl groups can be confirmed by FTIR spectroscopy. Moreover, we often combine FTIR and ¹³C solid-state nuclear magnetic resonance spectroscopy for studying the The degrees of vinyl acrylate (VA) substitution (DS). At BOC Sciences, DS is quantified by FTIR intensity measurements and local asymmetry.

Elementary Analysis (EA)

The elementary analysis method provides a simple and powerful method for the determination of the DS values of homosubstituted and heterosubstituted (mixed) esters of cellulose or amylose. Samples in the whole DS-range can be analyzed, and BOC Sciences has introduced state-of-the-art EA instruments capable of providing accurate analysis of cellulose or amylose mixed derivatives such as ethers or even ester-ethers. Our experts perform the elemental analysis to obtain more precise information about the DS achieved.