UV–vis Imaging of Piroxicam Supersaturation, Precipitation, and Dissolution in a Flow-Through Setup

Abstract

Evaluation of drug precipitation is important in order to address challenges regarding low and variable bioavailability of poorly water-soluble drugs, to assess potential risk of patient safety with infusion therapy, and to explore injectable in situ suspension-forming drug delivery systems. Generally, drug precipitation is assessed in vitro through solution concentration analysis methods. Dual-wavelength UV-vis imaging is a novel imaging technique that may provide an opportunity for simultaneously monitoring changes in both solution and solid phases during precipitation. In the present study, a multimodal approach integrating UV-vis imaging, light microscopy, and Raman spectroscopy was developed for characterization of piroxicam supersaturation, precipitation, and dissolution in a flow-through setup. A solution of piroxicam dissolved in 1-methyl-2-pyrrolidinone was injected into a flowing aqueous environment (pH 7.4), causing piroxicam to precipitate. Imaging at 405 and 280 nm monitored piroxicam concentration distributions during precipitation and revealed different supersaturation levels dependent on the initial concentration of the piroxicam solution. The combination with imaging at 525 nm, light microscopy, and Raman spectroscopy measurements demonstrated concentration-dependent precipitation and the formation, growth, and dissolution of individual particles. Results emphasize the importance of the specific hydrodynamic conditions on the piroxicam precipitation. The approach used may facilitate comprehensive understanding of drug precipitation and dissolution processes and may be developed further into a basic tool for formulation screening and development.

Surface Dissolution UV Imaging for Investigation of Dissolution of Poorly Soluble Drugs and Their Amorphous Formulation

“…Drug supersaturation, which often precedes precipitation, is conventionally determined in vitro through solubility and solution concentration comparison. A recent study conducted using UV-vis imaging, light microscopy and Raman spectroscopy has characterised the piroxicam supersaturation, precipitation and dissolution in an enclosed flow-through casing (15). A study by Sun et al (15) is different as crystalline drug and dissolved drug were inserted instead of the API or formulation that was used in the present study.…”

“…A recent study conducted using UV-vis imaging, light microscopy and Raman spectroscopy has characterised the piroxicam supersaturation, precipitation and dissolution in an enclosed flow-through casing (15). A study by Sun et al (15) is different as crystalline drug and dissolved drug were inserted instead of the API or formulation that was used in the present study. Our study also reveals that hydrodynamic conditions such as flow rate and flow pattern influence the rate and extent of drug precipitation (15).…”

“…A study by Sun et al (15) is different as crystalline drug and dissolved drug were inserted instead of the API or formulation that was used in the present study. Our study also reveals that hydrodynamic conditions such as flow rate and flow pattern influence the rate and extent of drug precipitation (15). Furthermore, swelling, crystal growth and/or precipitation at the compact surface can be detected as it has also been shown for the metastable forms of amlodipine besylate where the amorphous salt, the crystalline anhydrate and dihydrate salt forms as well as the amlodipine free base were confirmed (21).…”

“…A supersaturated drug solution is thermodynamically unstable compared to the equilibrium condition (saturation). Thus, it has the tendency to return to the equilibrium state (lowest chemical potential) by drug precipitation (15). The higher the supersaturation, the more precipitation will take place as the former is the driving force for the latter (16).…”

Towards a better understanding of the release mechanisms of caffeine from PLGA microparticles

“…Poly(lactic‐ co ‐glycolic acid) (PLGA) is frequently used as a polymeric matrix former in controlled drug delivery systems, in particular microparticles, scaffolds, nanofibers, and implants . This type of advanced drug products allows to preprogram the release rate of the active agent into the human body after injection or implantation.…”