Molecules derived from cellulose such as hydroxyethyl cellulose are widely used in the pharmaceutical industry. Such macromolecules are often utilized as viscosity modifiers for different products such as moisturizing creams, eye drops and as excipients in a wide range of applications. To that end, standard analysis of cellulose derivatives has focused on measuring the sample’s intrinsic viscosity and molecular weight distribution. The aim of this analysis is to comprehend how the viscosity is affected by the addition of the cellulose derivative to an existing solution/process.
Miscalculation of the quantity of cellulose required to change the viscosity will not only prevent the realization of the desired increase, but may also increase the pumping and other processing expenditures. Prior to mixing the cellulose into the existing solution, users should examine the cellulose so that they know how much of the cellulose must to be added, how to grade or blend the sample, or whether to look for another source of cellulose if the evaluated batch does not meet their specifications.
Size-exclusion chromatography (SEC) or gel permeation chromatography (GPC) technique is extensively used for the characterization of a wide range of macromolecules, ranging from proteins to bulk manufactured polymers. This method can be utilized to determine the molecular weight distribution, molecular weight moments, the intrinsic viscosity, and the hydrodynamic size of these macromolecules. Figure 1 shows a complete setup for a GPC system.
Figure 1. Malvern Panalytical OMNISEC triple detection GPC system.
This article demonstrates how the OMNISEC triple detection system from Malvern Panalytical is used to analyze a wide range of aqueous cellulose derivatives. It also shows the slight yet clear variations between these different derivatives which can be parsed out by the OMNISEC triple detection GPC system.
For GPC analysis, four cellulose derivative samples were formulated in an aqueous mobile phase of 0.05M Na2SO4. The samples used were hydroxybutylmethylcellulose (HBMC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), and hydroxypropylmethylcellulose (HPMC). A standard triple detector chromatogram using the HEC samples is shown in Figure 2. Here, the refractive index detector signal is shown in red, the low angle light scattering (LALS) in black, the right angle light scattering (RALS) signal in green, and the viscometer signal in blue. The measured molecular weight at each retention volume is shown in gold to observe the molecular weight distribution of the sample.
Figure 2. Triple detector chromatogram of HEC.
Summary of Results
Table 1 compares the molecular information achieved for the four cellulose derivative samples. Presented values comprise the intrinsic viscosity ([η]), moments of molecular weight distribution (Mw, Mn and Mz), and hydrodynamic radius (Rh).
Table 1. Molecular data derived for the cellulose derivative samples.
Table 1 shows that the HBMC sample and the HPC sample have the highest and lowest viscosity [η], respectively. Similarly, the HBMC sample has the highest Mw and the HPC sample has the lowest. This trend of increasing [η] and increasing Mw is anticipated and these measurements only give the average numbers about the samples in their entirety.
The Mark-Houwink plot (Figure 3) provides a more detailed way of viewing the effect of these samples on the solution’s viscosity. This plot reveals the [η] of the sample at each Mw across the whole molecular weight distribution. Samples that are more open in solution are higher on the plot, whereas samples that are more closely packed in solution are lower at a given molecular weight. Likewise, samples having a more open structure will increase the viscosity of a solution when compared to higher density samples.
Figure 3. Mark-Houwink overlay plot of duplicate injections of samples of HEC (black & green), HPC (red & purple), HPMC (grey & cyan), and HBMC (blue & olive).
In Figure 3, the HBMC sample appears the least dense, and the HPC sample is the densest. Cellulose derivatives can be compared with analogous structures where HBMC is less dense than that of HPMC and HEC is less dense than that of HPC. Initially, this may look counterintuitive in that the longer alkyl chain raises the density in the first comparison (HPC and HEC) and reduces it in the second (HBMC and HPMC). One possible explanation for this is variations in the degree of substitution of butyl, propyl, ethyl, or methyl groups, which is not known in these samples.
Malvern Panalytical’s OMNISEC triple detection GPC system has been utilized to examine samples of cellulose derivatives. The variations between the samples can be distinctly seen with respect to the molecular weight distribution, molecular weight as well as the molecular structure in the form of a Mark-Houwink plot.
The variations thus viewed between the samples can be utilized in the pharmaceutical industry to compare their molecular characteristics with their performance, for example, as viscosity modifiers or excipients. The characterization of such samples would allow them to be suitably blended so that the preferred performance properties can be reliably obtained.
The performance of the OMNISEC triple detection GPC system in terms of its refractive index sensitivity and light scattering, along with its robustness and ease-of-use with self-balancing viscometer, makes it the ultimate system for performing these measurements.
This information has been sourced, reviewed and adapted from materials provided by Malvern Panalytical.
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