Sunday, May 24, 2009



Cellulose esters are heavily used for controlled drug delivery

Cellulose derivatives, widely found in foods and pharmaceuticals, are used as emulsifiers, dispersing agents, and thickeners. While cellulose itself is not readily soluble in water, various derivative esters have increased solubility, even if these esters are hydrophobic in nature. This seemingly contradictory behavior occurs because the ester groups disrupt the cellulose crystalline structure. In addition to solubility, various esters have different glass transition temperatures, tensile strengths, and water vapor transmission rates. The amount and type of esterification present in cellulose material therefore becomes exceedingly important when considering its use in pharmaceuticals or food products.

This article will discuss the discriminant analysis of cellulose esters using Fourier transform near infrared (FT-NIR) spectroscopy. The article will provide an overview of cellulose derivatives, looking at how cellulose acetate esters are heavily exploited in pharmaceuticals, where they are typically used for controlled drug delivery. Current methods will be discussed, along with the issues affecting available technologies. Emerging methods and future developments-and their effects on the pharmaceutical and drug delivery market in general-will also be considered. The purpose of this article is to demonstrate that an FT-NIR analyzer can quickly and accurately identify and classify cellulose esters.

Figure 1. Release Rate in Acidic Conditions

Typical dissolution profile for a drug compounded with various cellulose acetate esters.


Good Excipients and Coatings

Cellulose acetate esters are used a great deal in pharmaceuticals, typically for controlled drug delivery. Their controlled porosity and solubility make them good excipients and coatings for solid dosage forms. Each sugar residue in cellulose has three hydroxyl groups that are amenable to esterification. Quantitative measurement of the amount of ester present is reported either by percent or by degree of substitution (DS). The DS of a particular material, which will fall between zero and three, indicates the average number of ester groups found on each residue.

To provide for greater complexity, cellulose acetate materials are further derivatized with proprionate or butyrate groups to various degrees. As a result, a given cellulose material may primarily be a cellulose acetate with additional proprionate or butyrate ester groups. The sheer variety of available esters allows a great deal of control over how a drug performs after ingestion.

FT-NIR spectroscopy can be used to confirm the identity of cellulose esters with great speed and accuracy; it has proven to be a superior method for identifying and classifying different materials. FT-NIR uses the part of the electromagnetic spectrum between the UV-visible and the mid-infrared regions to detect overtone and combination vibrations present in nearly all organic molecules. The unique structure of specific organic molecules allows them to generate characteristic spectral patterns when irradiated with near-infrared light.

As a spectroscopic technique, FT-NIR can generate results in seconds without sample preparation or destruction, a clear advantage over other spectroscopic methods. Because FT-NIR spectroscopy can discriminate among similar raw materials, a Thermo Scientific Antaris FT-NIR analyzer was chosen to analyze different cellulose acetate esters for this study.

A Range of Materials

Identity and characteristics of cellulose materials used in the experiments.

Nine cellulosic materials were obtained from Eastman Chemical Company (Kings-port, Tenn.) or Acros Organics (Fair Lawn, N.J.). The materials represented a range of type and degree of esterification. While microcrystalline cellulose had no ester groups present, the others were acetate esters with various amounts of additional proprionyl or butyryl moieties (see Table 1, above).

Three samples of each material were taken and placed in glass vials. The samples were analyzed three or four times using the integrating sphere module, for a total of ten scans for each material. Between scans, the contents in the vials were shaken and then compacted by gently rapping the vial on a solid surface. This method ensured consistency in the density of the material while simultaneously effecting variety in sampled material. The samples were scanned between 10,000 and 4,000 cm-1 at a resolution of 8 cm-1 with 16 scans per analysis. No attenuator screen was in place, and a 1X gain was used. Baseline offsets were minimized by analyzing the data as first-derivative spectra. The data demonstrated the variation among the different cellulose materials in the first derivative spectra as well as the regions used in the chemometric analysis.

Discriminant analysis was performed using Thermo Scientific TQ Analyst software. The multiplicative signal correction option was chosen for the path length, and Norris smoothing (segment length = 5; gap = 5) was performed. Additionally, unique distributions were calculated for each class using a technique commonly referred to as SIMCA (soft independent modeling of class analogy). A principal component scores plot shows exceptionally clear discrimination among the various cellulose ester types. The cellulose acetate butyrate esters are widely separated from each other and the other cellulose derivatives; the cellulose acetate proprionate esters require a different region to discriminate. The data show that the spectral differences among these materials range from 5,050 to 4,800 cm-1. A second chemometric analysis on this region using similar parameters allowed discrimination between these proprionate esters (see Figure 2a and 2b, p. 48).

Validating Analysis

To validate the effectiveness of this analysis, new samples of the cellulose materials were obtained and scanned. These materials were then classified according to the chemometric analysis described above (see Table 2, p. 47). All of the test samples were correctly identified and placed into their proper classes. The data indicate that the method is suitable for identifying new samples of the cellulose materials.

Cellulose acetate esters are used a great deal in pharmaceuticals, typically for controlled drug delivery. Their controlled porosity and solubility make them good excipients and coatings for solid dosage forms.

Validation samples were analyzed using the parameters determined from the calibration materials. All of the validation samples were correctly identified.

Figure 2a. Spectral differences among sample materials

Spectral variation was between 5,050 and 4,800 cm-1 for the cellulose acetate proportionate esters.

Figure 2b. A chemometric analysis of sample materials

A principal component scores plot indicating good discrimination between the cellulose acetate proportionate esters.

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