Microparticles formation of anti-inflammatory drug with bio-degradable polymer

Multi-scale and/or multi-disciplinary approach to process-product innovation

Controlled Release of the Active Ingredient: Mechanisms, Devices & Analysis (T3-2)

Dr Ljudmila Fele Zilnik
National Institute of Chemistry
Laboratory for Process Engineering
Hajdrihova 19, P.O.Box 660, SI-1001 Ljubljana
Slovenia

Dr Andrej Krzan
National Institute of Chemistry
Laboratory for Polymer Chemistry and Technology
Hajdrihova 19, 1001 Ljubljana
Slovenia

Dr Detlef Freitag
University of Erlange-Nuernberg
Chair of Separation Science and Technology, High Pressure Laboratory
Haberstrasse 11, 91058 Erlangen
Germany

Keywords: supercritical antisolvent precipitation, poly(lactide), dimethylsulfoxide, diclofenac sodium

Supercritical antisolvent precipitation, a semicontinuous precipitation technique, is widely used to produce micrometric and sub-micrometric particles of pharmaceutical and related compounds like hydrophobic enzymes, anti-inflammatory drugs, antibiotics, biopolymers. Employing SCF-GAS technique, where the application of an antisolvent decreases the solubility of a material dissolved in the solution, can form micro-particles, where the drug is embedded into degradable polymer matrix. This technique is applicable to the material, if the compound is insoluble (or slightly soluble) in the gas and the gas is (very) soluble in the liquid. For a successful operation, a good solvent-antisolvent combination has to be chosen. The solubility of solid substances in the chosen solvents is essential for evaluating the feasibility of a process and for establishing optimum process conditions.
In the present work, preliminary experiments on the formation of micro particles for pharmaceutical purposes have been done by employing the GAS technique. The drug of interest was diclofenac sodium, a non-steroidal active substance that acts anti-inflammatory, with prolonged release, used in the treatment of rheumatic disorders. The substance, 2-[(2,6-Dichlorophenyl) amino]benzeneacetic acid sodium salt is a weak acid with a pKa of 4 and a partition coefficient (n-octanol/aqueous buffer, pH 7.4) of 13.4. Different copolymers can be used as the drug carrier to reach the right physical and chemical properties and adjust polymer degradation and erosion. As a first step, a linear biodegradable polyester poly (lactide), biochemical inert, nontoxic with FDA approval and not too expensive was used. The experiments were performed by using dimethylsulfoxide (DMSO) and a mixture of DMSO, dichloromethane as solvent and supercritical carbon dioxide as anti-solvent. The experiments were focused on the exploration of favorable operating conditions to yield the appropriate micro particles.

Presented Tuesday 18, 11:00 to 11:20, in session Controlled Release of the Active Ingredient: Mechanisms, Devices & Analysis (T3-2).