Effect of Formulation Additives on Drug Transport through Size-Exclusion Membranes
| Autor: | Konstantin Tsinman, Oksana Tsinman, Enikő Borbás, Bálint Sinkó, Krisztina Takács-Novák, Petra Tőzsér, Zsombor Kristóf Nagy, Gergely Völgyi |
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| Rok vydání: | 2018 |
| Předmět: |
Cell Membrane Permeability
Pyrrolidines Vinyl Compounds Drug Compounding Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Polyethylene Glycols Excipients 03 medical and health sciences 0302 clinical medicine Drug Development Drug Discovery Particle Size Solubility Dissolution Antihypertensive Agents Supersaturation Aqueous solution Chemistry Regenerated cellulose Permeation 021001 nanoscience & nanotechnology Solvent Membrane Chemical engineering Molecular Medicine Carvedilol Polyvinyls 0210 nano-technology |
| Zdroj: | Molecular Pharmaceutics. 15:3308-3317 |
| ISSN: | 1543-8392 1543-8384 |
| Popis: | The aim of this research was to investigate the driving force of membrane transport through size-exclusion membranes and to provide a concentration-based mathematical description of it to evaluate whether it can be an alternative for lipophilic membranes in the formulation development of amorphous solid dispersions. Carvedilol, an antihypertensive drug, was chosen and formulated using solvent-based electrospinning to overcome the poor water solubility of the drug. Vinylpyrrolidone-vinyl acetate copolymer (PVPVA64) and Soluplus were used to create two different amorphous solid dispersions of the API. The load-dependent effect of the additives on dissolution and permeation through regenerated cellulose membrane was observed by a side-by-side diffusion cell, μFLUX. The solubilizing effect of the polymers was studied by carrying out thermodynamic solubility assays. The supersaturation ratio (SSR, defined as the ratio of dissolved amount of the drug to its thermodynamic solubility measured in exactly the same medium) was found to be the driving force of membrane transport in the case of size-exclusion membranes. Although the transport through lipophilic and size-exclusion membranes is mechanistically different, in both cases, the driving force of membrane transport in the presence of polymer additives was found to be the same. This finding may enable the use of size-exclusion membranes as an alternative to lipid membranes in formulation development of amorphous solid dispersions. |
| Databáze: | OpenAIRE |
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