A prototype single-port device for pressurized intraperitoneal aerosol chemotherapy. Technical feasibility and local drug distribution

Abstract Purpose: To evaluate the technical feasibility and homogeneity of drug distribution of pressurized intraperitoneal aerosol chemotherapy (PIPAC) based on a novel process of intraperitoneal drug application (multidirectional aerosolization). Methods: This was an in vivo experimental study in pigs. A single-port device was manufactured at the smallest diameter possible for multidirectional aerosolization of the chemotherapeutic drug under positive intraperitoneal pressure. Four domestic pigs were used in the study, one control animal that received multidirectional microjets of 9 mL/sec for 30 min and three animals that received multidirectional aerosolization (pig 02: 9 mL/sec for 30 min; pigs 03 and 04: 3 mL/sec for 15 min). Aerosolized silver nitrate solution was applied for anatomopathological evaluation of intraperitoneal drug distribution. Results: Injection time was able to maintain the pneumoperitoneum pressure below 20 mmHg. The rate of moderate silver nitrate staining was 45.4% for pig 01, 36.3% for pig 02, 36.3% for pig 03, and 72.7% for pig 04. Conclusions: Intra-abdominal drug distribution had a broad pattern, especially in animals exposed to the drug for 30 min. Our sample of only four animals was not large enough to demonstrate an association between aerosolization and a higher silver nitrate concentration in the stained abdominal regions.

Bioequivalence of Orally Inhaled Drug Products : Focus on Current Regulatory Perspectives.

Asthma/chronic obstructive pulmonary disease (COPD) medication market is a fast growing market, especially in the emerging markets where drugs have not been launched due to high costs. Use of generic medicines has been increasing in recent years, primarily as a cost saving measure in healthcare provision. Orally inhaled products (OIPs) should continue to remain an attractive clinical proposition. At the same time, establishing bioequivalence of an inhaled therapeutic can be a challenging proposition. The purpose of establishing bioequivalence is to demonstrate equivalence between the generic medicine and the originator medicine in order to allow bridging of the pre-clinical and clinical testing performed on the originator drug. Methodologies to determine bioequivalence are well established for oral, systemically acting formulations. However, for inhaled drugs, there is currently no universally adopted methodology, and regulatory guidance in this area has been subject to debate. There is no one-size-fits-all programme. This review article mainly focused on current regulatory perspectives on bioequivalence of topically acting, orally inhaled drug products.

Aerosol delivery systems in childhood asthma.

Asthma in younger children appears to be increasing in prevalence, whilst at the same time it is recognized that inhaled corticosteroids and bronchodilators are the mainstay of treatment for this condition. Presently the devices available for aerosol treatment of young children are mostly developed for use in older children and adults. However, an awareness of the need for delivery systems dedicated to use by young children is increasing. The devices available at present for aerosol treatment of young children comprises the nebulizer, metered-dose inhaler with spacer, and dry powder inhaler. The inhaler strategy found most useful at present can be summarized as follows: children younger than 2 years can use MDI+spacer+mask or nebulization, while children above 2 years can use MDI+spacer (without mask). Older children (3-4 years) can be easily taught the use of a Rotahaler.