Puerarin dry powder inhaler formulations for pulmonary delivery: Development and characterization

Abstract

This study aims at developing and characterizing the puerarin dry powder inhaler (DPI) formulations for pulmonary delivery. The inhalable particles size (<2 μm) was accomplished by micronization and its morphology was examined by scanning electron microscopy (SEM). The puerarin-excipient interaction in powder mixtures was analyzed by using Fourier transform infrared spectroscopy (FTIR), Raman confocal microscopy, X-Ray powder Diffraction (XRD), and differential scanning calorimetry (DSC) methods. Using a Twin stage impinger (TSI), the in-vitro aerosolization of the powder formulations was carried out at a flow rate of 60 L/min and the drug was quantified by employing a validated HPLC method. No significant interactions between the drug and the excipients were observed in the powder formulations. The fine particle fraction (FPF) of the drug alone was 4.2% which has increased five to six-fold for the formulations with aerosolization enhancers. Formulation containing lactose as large carriers produced 32.7% FPF, which further increased with the addition of dispersibility enhancers, leucine and magnesium stearate (40.8% and 41.2%, respectively). The Raman and FTIR techniques are very useful tool for understanding structural integrity and stability of the puerarin in the powder formulations. The puerarin was found to be compatible with the excipients used and the developed DPI formulation may be considered as an efficient formulation for pulmonary delivery for the management of various diseases at a very low dose.

Impact of Leucine and Magnesium Stearate on the Physicochemical Properties and Aerosolization Behavior of Wet Milled Inhalable Ibuprofen Microparticles for Developing Dry Powder Inhaler Formulation

“…However, the subtracted results ( Figure 3 B) showed no remarkable change (red circle) observed among IBF microparticles and excipients. A minor shift in the absorption peak of original IBF occurred due to the presence of possible -OH bonds in lactose and leucine [ 1 , 4 ]. Thus, no specific chemical changes or interaction were noticed among the drug and excipients from the developed DPI formulations.…”

“…Finally, the suspension was homogenized using a high shear homogenizer (Heidolph DIAX 900, Labexchange, Burladigen, Germany) at 17,000 rpm for 30 min in an iced water bath at 5–8 °C. Dry milled IBF microparticles were prepared using a mortar and pestle with the hand milling method [ 1 , 3 , 4 ]. The size of the micronized IBF microparticles was determined by Malvern mastersizer 3000 until we produced the desired size (1–5 µm) and was visualized by scanning electron microscopy (SEM).…”

“…The amount of IBF was determined by means of a validated HPLC assay method. This test was accomplished with a mean drug content of 100 ± 5% (Mean ± Standard Deviation) with a coefficient of variation of <5% for all the DPI formulations [ 1 , 3 , 15 ]. After determining % CV, each formulated powder mixture was manually filled in a hard gelatine capsule shell (Size 3).…”

“…The pulmonary drug delivery system is one of the most preferred routes of drug administration as it delivers drugs directly into the deep lungs, avoids the first-pass metabolism, and produces therapeutic benefits at a very low dose. The DPI formulation provides deep drug deposition of drugs through the patient’s respiration force [ 1 , 2 ]. DPI formulations consist of inhalable sized micronized drug particles (<5 µm), which are produced by the traditional micritization method.…”

“…The micronized inhalable drug particles are highly cohesive and produce a poor flow property that limits the aerosolization and efficient lung deposition of drugs. To overcome these problems, the micronized drug particles are mixed with large carriers (lactose) and dispersibility enhancers such as leucine and MgSt [ 1 , 3 , 4 ]. This study investigated the preparation of micronized particles of a model drug by a wet milling method and determined the role of leucine and magnesium stearate in aerosolization behavior for the development of an efficient DPI formulation.…”