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Measuring Ingredient-Specific Particle Size Distribution Using Wide-Field Raman Chemical Imaging.
Work performed in collaboration with the U.S. Food and Drug Administration.
Intranasal drug delivery is an attractive delivery method for a broad range of pharmaceuticals that treat a variety of diseases. This patient-friendly delivery method can provide multiple benefits including faster onset, reduction in potential side effects and increased compliance of the drug treatment.
Creating the correct nasal formulation is both challenging and critical. Particle size directly correlates to drug effectiveness, active pharmaceutical ingredient (API) bioavailability and bioequivalence. Nasal sprays formulated as suspensions typically contain micronized API in the presence of numerous excipient materials. Although particle size distribution (PSD) of the drug can be easily determined prior to the formulation, it has been a challenge to determine ingredient-specific PSD in the finished product.
Particle sizing techniques based on laser scattering, cascade impaction or optical image analysis cannot discriminate between particles of API and those of an excipient or a surfactant. Multi-stage cascade impaction followed by extraction and HPLC analysis is an option, but can be extremely time consuming and labor-intensive and is not very reproducible. Consequently, the development of an efficient ingredient-specific approach is essential for ensuring that all ingredients fall into the proper size range, particularly during the early stage of product development.
The images shown here are representative of on-going studies being performed in collaboration with the FDA using the FALCON II™ Wide-Field Raman Chemical Imaging system to determine chemical identity, particle size and particle size distribution (PSD) of micronized drug substance in aqueous suspension nasal spray formulations. Studies are being conducted with the long-term goal of establishing a fully validated in vitro particle sizing method for measuring bioequivalance of nasal drug delivery products. In vitro methods are frequently preferred over in vivo methods, which are often costly, time consuming and inconclusive.
ChemImage’s FALCON II Wide-Field Raman Chemical Imaging system efficiently collects millions of spectrally unique data points at sub-micron spatial resolution. The FALCON II Wide-Field Raman Chemical Imaging system measured PSD of API and the excipient in a nasal spray suspension. The Raman chemical image in Figure 1 is comprised of 442,225 individual spectra collected at a rate of >100 spectra/seconds. The histogram in Figure 2 shows the distribution of 43 API particles in 25 fields of view calculated by CI Xpert™ software. The mean API particle size is 1.8 ± 1.2 µm.
API particles are clearly distinguishable from those of excipients. The FALCON II Wide-Field Raman Chemical Imaging system is able to differentiate between and identify the chemical makeup of multiple components in complex mixtures.
Acquisition rates surpass the speed of competing point and line mapping systems. The substantial time and labor savings are ultimately transformed into cost savings and a reduced time to market.
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