Surface analysis in pharmaceutical research

From the distribution of the active pharmaceutical ingredient to impurities on or in blister packages

Pharmaceutical research is a multi-faceted field. The development of new active pharmaceutical ingredients, the improvement of existing drug formulations (galenics) and their dosage forms (drug delivery) are important areas of research. Recent developments in the field of anti-diabetics form a classic example of the latter. Many patients find insulin injections unpleasant. Therefore, alternatives are sought to allow for the safe and non-invasive administration of insulin (e.g., in the form of tablets, patches, or sprays). However, such developments require a suitable analytical support as the following example shows:

Insulin

Oral delivery of insulin

Spray instead of syringe - Supporting XPS analysis for the development of new dosage forms

The oral intake of insulin is developed as an alternative to the widespread injection of this hormone. Suitable insulin carriers are bio-degradable nanoparticles that encapsulate the insulin and release it only after it has reached the blood stream. The quality of the nano-encapsulation and the amount of encapsulated hormone are crucial for the efficacy of the oral administration. Therefore, surface-sensitive XPS studies have been combined with bulk-analytical methods to obtain qualitative and quantitative information about the quality of the insulin encapsulation.

Basically, the uncharged nanoparticles and insulin provide very similar XPS spectra. These show signals of the main elements C, O and N. In the XPS spectrum, however, insulin can be differentiated from the nanoparticles used on the basis of its characteristic disulfide bridge (Cys-S-S-Cys), as shown by the S2p detail spectrum in the above figure. Due to the disulfide bridges, the insulin provides signals with an S2p3 / 2 binding energy (BE) of 163.5 eV. The SO32 / SO42 bonds (BE ca. 168 eV), which have also been detected, can be assigned to a sulfur component present on the nanoparticles.

Due to the information depth of the method, the XPS succeeds in quantitatively recording the insulin in the top 10 nm of a nanoparticle. A comparison with the results of a total ­ volume ­ determination of the insulin ­ content thus allows an estimate of the surface portion of the hormone.

Table 1 shows examples of results of two nanoparticle batches. While the total insulin content of both batches is almost identical, the XPS data show a significantly higher insulin content on the surface of batch # 2. In addition, the insulin content of this batch can be significantly reduced by washing. This indicates a faulty or incomplete encapsulation of the hormone. Corresponding nanoparticles are unsuitable as carriers of insulin for oral administration.

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