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Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is gaining acceptance in clinical practice, but detailed information about the microinjection pump (MIP®), the generated aerosol and drug distribution is missing.Analytical Methods: Ex vivo granulometric analyses by means of laser diffraction spectrometry were performed for MIP® aerosol characterization. Beside the standard operation conditions, the impact of the volumetric liquid flow rate on the aerosol characteristics was investigated with different liquids. Granulometric results as well as the local drug distribution were verified by ex vivo gravimetric analyses. On the basis of determined MIP® characteristics, the aerosol droplet size, which is necessary for a homogenous intra-abdominal drug distribution, was calculated.Results: Granulometric analyses showed that the MIP® aerosol consists of a bimodal volume-weighted particle size distribution (PSD3) with a median droplet diameter of x 50,3 = 25 µm. Calculations reveal that the droplet size for a homogenous intra-abdominal drug distribution during PIPAC therapy should be below 1.2 µm. We show that >97.5 vol% of the aerosolized liquid is delivered as droplets with ≥3 µm in diameter, which are primarily deposited on the surface beneath the MIP® by gravitational settling and inertial impaction. These findings were confirmed by ex vivo gravimetric analyses, where more than 86.0 vol% of the aerosolized liquid was deposited within a circular area with a diameter of 15 cm.Conclusions: The granulometric aerosol properties, as well as the aerodynamic conditions achieved by standard MIP® operation, do not support the idea of widespread or homogenous drug distribution in the abdominal cavity. [ABSTRACT FROM AUTHOR]

Purpose: Temozolomide dry powder formulations for inhalation, performed with no excipient or with a lipid or lactose coating, have been evaluated. Methods: The particle size of raw temozolomide in suspension was reduced by a high-pressure homogenizing technique, and the solvent was evaporated by spray-drying to obtain a dry powder. The physicochemical properties of this powder were evaluated and included its crystalline state, thermal properties, morphology, particle size and moisture and drug content, and these properties were determined by X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, laser light scattering, thermogravimetric analysis and high-performance liquid chromatography, respectively. The aerodynamic properties and release profiles were also evaluated using a multistage liquid impinger and a modified USP type 2 dissolution apparatus adapted for inhaler products, respectively. Results: The dry powder inhalation formulations had a high temozolomide content that ranged from 70% to 100% in the crystalline state and low moisture content. Aerodynamic evaluations showed high fine-particle fractions of up to 51% related to the metered dose. The dissolution profile revealed a similarly fast temozolomide release from the formulations. Conclusions: Dry temozolomide powder formulations, based on the use of acceptable excipients for inhalation and showing good dispersion properties, represent an attractive alternative for use in local lung cancer therapy. [ABSTRACT FROM AUTHOR]