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Investigation of Pharmaceutical Dosage Forms

The Golden Gate Diamond ATR is now over 25 years old but remains at the forefront of research in materials and pharmaceutical formulation and many other areas.

Investigation of pharmaceutical dosage forms

A pharmaceutical formulation is the process by which the bioactive component in a medicine is processed into a stable form, by which the correct dosage may be administered safely to the patient. The correct dose of a medicine may be far too small for practical application in its raw form. Instead, the active ingredient is formulated with a number of other compounds, called excipients, which make up the physical bulk of most tablets and capsules, but these same excipients also have a vital role in supporting the stability of the active ingredients during manufacture.1,2

During the pre-formulation phase, studies may be undertaken to assess the effect of excipients or manufacturing processes on the stability, delivery, or bioavailability of the active ingredient. The bioavailability is mainly a function of its solubility in aqueous and lipid environments and therefore much research has been directed at ways of improving dissolution and absorption characteristics.3,4

These studies are particularly needed for the characterisation of novel pharmaceutic agents. One such category of substances is proteins, whose characteristic secondary and tertiary structures may easily be disrupted by heat and mechanical stress. Processes used during the formulation of a drug, such as spray-drying, are a potential cause of protein denaturation due to their tendency to migrate towards the air–liquid interface at the surface of droplets.2

In one combined infrared and terahertz spectroscopy study, the dielectric relaxation processes which signal the mobility of proteins within a formulation were studied. The effects of three commonly used excipients, trehalose, L-arginine HCl, and polysorbate 20 on formulations with the model protein Bovine Serum Albumin (BSA) were the targets of this work. The terahertz time-domain spectroscopy study (THz-TDS) revealed the temperature dependent transitions between two modes of relaxation, one of which is considered indicative of large-scale mobility and the macromolecular level, and the other small-scale. FT-IR spectroscopy, on the other hand, is sensitive to changes in the protein secondary structure. This was investigated using a heated Golden Gate ATR accessory over a temperature ramp from 303.15 K to 393.15 K to provide a context for the changes observed in the THz-TDS spectra.2

In another study, drug loading within mesoporous silica carriers was investigated using ATR FT-IR spectroscopic imaging. A hot melt process was used to load the model API (Ibuprofen) into the silica carrier. In situ hot melt loading and dissolution studies, involving a temperature ramp from ambient to 80 °C followed by dissolution in a phosphate buffer were carried out on a Golden Gate ATR using a flow cell attachment specially designed by the researchers. The resulting spectra showed the process by which crystalline ibuprofen is absorbed into pores within the compacted mesoporous silica during heating and then, during dissolution, partly recrystallised in the vacant holes left by the original crystals.4

Sustainable food packaging

There has been much effort in recent years to avoid excessive use plastics and other packaging, whose disposal represents an increasing problem. Alternative, sustainable sources of packaging derived from plant waste, as part of a circular economy, are of great interest to researchers. In addition to this, the use of naturally occurring agents within packaging materials can help increase shelf life by preventing microbial decay of foodstuffs, thereby minimising food waste.5,6

Polyhydroxyalkanoates (PHAs) are a class of naturally biodegradable polymers which require modification by various treatments in order to provide good mechanical properties and be compatible with typical manufacturing processes.7

The polymeric nature of these materials makes them ideal for studying by FT-IR spectroscopy. Blends of different PHAs from mixed microbial cultures were studied by one group, prepared as thin mats suitable for food packaging by the electrospinning process. The prepared films were subjected to a temperature ramp experiment on the Golden Gate diamond ATR from 30 °C to 180 °C in order to investigate the changes in molecular ordering as the bioplastic reached its melting point.5

Another bio-based application for food packaging is the use of essential oils from plants as antimicrobial coatings. Active packaging materials contain agents which are released from the material over time and act to stabilise food, increase its shelf-life, or have antimicrobial properties. ATR FT-IR combined with chemometric tools such as PLS have been used successfully to characterise and quantify these agents on packaging materials.6


  1. P. Furrer, “The central role of excipients in drug formulation”, European Pharmaceutical Review (2013).
  2. T.A. Shmool, M. Batens, J. Massant, G. Van den Mooter and J.A. Zeitler, “Tracking solid state dynamics in spray-dried protein powders at infrared and terahertz frequencies”, Eur. J. Pharm. Biopharm. 144, 244–251 (2019). https://doi.org/10.1016/j.ejpb.2019.09.013
  3. T.M. Jones, “Preformulation studies”, in Pharmaceutical Formulation: The Science and Technology of Dosage Forms. Royal Society of Chemistry (2018).
  4. D. Lizoňová et al. “Molecular-level insight into hot-melt loading and drug release from mesoporous silica carriers”, Eur. J. Pharm. Biopharm. 130, 327–335 (2018). https://doi.org/10.1016/j.ejpb.2018.07.013
  5. B. Melendez-Rodriguez et al., “Preparation and characterization of electrospun food biopackaging films of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) derived from fruit pulp biowaste” Front. Sustain. Food Syst. 2, 1–16 (2018). https://doi.org/10.3389/fsufs.2018.00038
  6. A.C.S. Valderrama and G.C. Rojas De, “Traceability of active compounds of essential oils in antimicrobial food packaging using a chemometric method by ATR-FTIR”, Am. J. Anal. Chem. 8, 726–741 (2017). https://doi.org/10.4236/ajac.2017.811053
  7. Z. Li, J. Yang and X.J. Loh, “Polyhydroxyalkanoates: opening doors for a sustainable future”, NPG Asia Mater. 8, e265 (2016). https://doi.org/10.1038/am.2016.48