Real-Time Quantitative Evaluation of a Drug during Liposome Preparation Using a Probe-Type Raman Spectrometer.

During the manufacturing process of liposome formulations, it is considered difficult to evaluate their physicochemical properties and biological profiles due to the complexity of their structure and manufacturing process. Conventional quality evaluation is labor-intensive and time-consuming; therefore, there was a need to introduce a method that could perform in-line, real-time evaluation during the manufacturing process. In this study, Raman spectroscopy was used to monitor in real time the encapsulation of drugs into liposomes and the drug release, which are particularly important quality evaluation items. Furthermore, Raman spectroscopy combined with partial least-squares (PLS) analysis was used for quantitative drug evaluation to assess consistency with results from UV-visible spectrophotometry (UV), a common quantification method. The prepared various ciprofloxacin (CPFX) liposomes were placed in cellulose tubes, and a probe-type Raman spectrophotometer was used to monitor drug encapsulation, the removal of unencapsulated drug, and drug release characteristics in real time using a dialysis method. In the Raman spectra of the liposomes prepared by remote loading, the intensities of the CPFX-derived peaks increased upon drug encapsulation and showed a slight decrease upon removal of the unencapsulated drug. Furthermore, the peak intensity decreased more gradually during the drug release. In all Raman monitoring experiments, the discrepancy between quantified values of CPFX concentration in liposomes, as measured by Raman spectroscopy combined with partial least-squares (PLS) analysis, and those obtained through ultraviolet (UV) spectrophotometry was within 6.7%. The results revealed that the quantitative evaluation of drugs using a combination of Raman spectroscopy and PLS analysis was as accurate as the evaluation using UV spectrophotometry, which was used for comparison. These results indicate the promising potential of Raman spectroscopy as an innovative method for the quality evaluation of liposomal formulations.

Potential application of novel liquid crystal nanoparticles of isostearyl glyceryl ether for transdermal delivery of 4-biphenyl acetic acid.

Novel liquid crystal nanoparticles (LCNs) composed of isostearyl glyceryl ether (GE-IS) and ethoxylated hydrogenated castor oil (HCO-60) were developed for the enhanced transdermal delivery of 4-biphenyl acetic acid (BAA). The physical properties and pharmaceutical properties of the LCNs were measured. The interaction between the intercellular lipid model of the stratum corneum and the LCNs was observed to elucidate the skin permeation mechanism. In the formulation, the LCNs form niosomes with mean particles sizes of 180-300 nm. The skin absorption mechanisms of LCNs are different, depending upon the application and buffer concentration. The LCNs composed of GE-IS and HCO-60 are attractive tools for use as transdermal drug delivery systems carriers for medicines and cosmetics, due to their high efficiency and safety.

Imaging Analysis Enables Differentiation of the Distribution of Pharmaceutical Ingredients in Tacrolimus Ointments.

We demonstrated the difference in the distribution state of pharmaceutical ingredients between tacrolimus (TCR) original ointment and six kinds of generic medicines. Two-dimensional imaging and depth analysis using attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy and confocal Raman microscopy were used, in addition to the evaluation of pharmaceutical properties, including spreading properties, rheological properties, and amount of solvent. The solvents, such as propylene carbonate and triacetin, in TCR ointments formed liquid droplets and dispersed in hydrocarbon oils. Waxes, white beeswax and beeswax, formed other domains. Confocal Raman microscopy could detect liquid droplet size without coalescence of that on germanium or glass surfaces. The combination of ATR FT-IR and confocal Raman imaging would be a powerful tool to reveal the size and shape of liquid droplets of pharmaceutical ingredients in semisolid formulations.