Clinically available pressurized metered-dose inhalers (pMDIs) mainly directly use micronized drugs as inhalable microparticles. Although technology for preparing pMDIs has proven to obtain clinically appropriate aerosol performance, the fine particle fraction and delivered dose content uniformity (DDCU) of pMDIs still need to be improved. DDCU problem is usually exacerbated by patients' handling errors prior to taking a dose. In this study, novel phospholipid microparticle inhalation pMDIs were prepared by a spray-freeze-drying process using mometasone furoate and formoterol fumarate dihydrate as model drugs and distearoylphosphatidylcholine as an excipient. Combined with the material composition, the atomization and freeze-drying processes were also studied. Our data showed that both atomization parameters of gas–liquid ratio and freeze-drying curve settings met the requirements of drug design. According to aerodynamic performance in vitro and DDCU evaluation, the performance of the phospholipid microparticle inhalation pMDI was better than that of the micronized drug microparticle pMDI. In conclusion, preparing pMDIs with particle engineering has the potential to ensure accuracy of quantification and to improve the efficiency of drug deposition in lungs in clinical practice.

The mometasone furoate (MF) and formoterol fumarate dihydrate (FF) inhalable microparticles prepared by different methods, such as micronized active pharmaceutical ingredients (APIs), microparticles of APIs prepared by spray-freeze drying technique (SFD APIs), and phospholipid microparticles of APIs prepared by SFD (SFD Lip-APIs), showed different inhaled drug delivery characteristics. Study on the physicochemical characteristics of those microparticles and the effect of matrix excipients on pharmacokinetic (PK) behaviors of inhalable microparticles is helpful for the development of new methods for inhalable microparticles with excellent performance of inhalation characteristics. In this study, the crystal state of the microparticles was investigated by powder X-ray diffraction and differential scanning calorimetry. The density was investigated by a bulk density method. The suspension and dispersion characteristics were determined by observing its state in hydrofluoroalkane (HFA). Meanwhile, the PK behaviors of SFD Lip-APIs in beagle dogs were also investigated by airway administration to evaluate the effect of phospholipids on drug release. The results indicated that the presence of phospholipids prevents the formation of solid bridges bonding to each other during SFD of pure drug solutions. In comparison to the conventional micronized microparticles, inhalable drug–phospholipid microparticles were easily dispersed and suspended in HFA. The embedded drugs were in a crystal state that endowed a better physical stability, and most interestingly, have similar PK behavior to the control (a mixed solution of MF/FF), suggesting that the phospholipids, as matrix excipients, had no effect on absorption. Given above, our designed SFD phospholipid microparticles may represent an efficient carrier for pulmonary delivery of MF and FF for further clinical treatment.

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Evolved over eons to encode biological assays, plants-derived natural products are still the first dawn of drugs. Most researchers have focused on natural compounds derived from commonly used Pimpinella species, such as P. anisum, P. thellungiana, P. saxifrage, and P. brachycarpa, to investigate their antioxidant, antibacterial, and anti-inflammatory properties. Ethnopharmacological studies demonstrated that the genus Pimpinella has the homology characteristics of medicine and food and mainly in the therapy of gastrointestinal dysfunction, respiratory diseases, deworming, and diuresis. The natural product investigation of Pimpinella spp. revealed numerous natural products containing phenylpropanoids, terpenoids, flavonoids, coumarins, sterols, and organic acids. These natural products have the potential to provide future drugs against crucial diseases, such as cancer, hypertension, microbial and insectile infections, and severe inflammations. It is an upcoming field of research to probe a novel and pharmaceutically clinical value on compounds from the genus Pimpinella. In this review, we attempt to summarize the present knowledge on the traditional applications, phytochemistry, and pharmacology of more than twenty-five species of the genus Pimpinella.