Development of a scaleable process for the fat emulsions production used in parenteral nutrition

Abstract

Parenteral nutrition is an extremely important nutrition method to assist in the hospitalized patient's recovery, especially those unable to use the enteral route, and important in diseases such as cancer, AIDS and disorders of the gastrointestinal tract. Data indicate that 80% of deaths in hospitalized patients are due to inability to obtain sufficient amounts of nutrients to sustain metabolic processes and maintain life. Traditionally, parenteral nutrition is carried out with the following components: amino acids, glucose and lipid emulsions. The lipid emulsion is a nanotechnological delivery system that must be formulated to ensure very low particle size average (less than 500nm) in the venous system for the administration in a secure manner. These formulations are part of a parenteral nutrition market that is expected to move up to USD 4.53 billion in 2017. Despite the significant growth of this market, Brazil does not hold the production technology for the fat emulsions used in parenteral nutrition. All products available in the Brazilian market are imported by multinational with factories in Europe, USA and Asia. In this context, the objective of this proposal is to develop a production process for the lipid emulsions used in parenteral nutrition. The results of this project can help to reduce the national deficit technology for the production of fat emulsions and increase the competitiveness of the domestic pharmaceutical industry. In addition, the commercialization of a national product will lead to an importation reduction, reducing overall costs to the country, and will improve the access to this important medicine that has a direct impact on public health. At this stage of the project, lipid emulsions will be developed in laboratory scale to determine a production engineering considering different process variables, such as concentration of ingredients, temperature, pressure and homogenization cycles. The development of the pre-emulsion and the high-pressure homogenization will be studied. Dynamic light scattering, laser diffraction and microscopic analysis, to determine the average particle size, polydispersity index and zeta potential value will characterize the formulations obtained. As required by section <729> of the American Pharmacopoeia (USP), the limit for the average particle size is 500 nm and the size of the larger particles, expressed in weight-percentage volume should not exceed 5¼m to a maximum 0.05%. The zeta potential should be in the range of - 20mV to -40mV. Therefore, the design challenge will be to obtain a stable lipid emulsion, scalable and commercially viable within the legal requirements for the product registration in the regulatory agencies (ANVISA, FDA). (AU)