Increasing levodopa and carbidopa loading quantity in oral pullulan thin film

Abstract

Due to the non-compliance of Parkinson’s patient, both youth and elderly patients commonly suffer from the consequent of tablet administration. Therefore, the way to solve this patient’s non-compliance is the development of levodopa (LD) and carbidopa (CD) as an oral thin film (OTF) formulation. The current study focuses on the increasing solubility of LD and CD in order to improve the loading quantity for OTF preparation including formulation development and short-term stability investigation. The technique of solubilization by ionization approach was selected. Quantitative determination of solubilized LD and CD in various acid solvents showed the highest solubility of both drugs in 0.1 M HCl acid/0.1 M citric acid pH 1.5. The utilization of cosolvency, surfactant and high polymer concentration were also applied. The result revealed that they were not provide synergistic effect on the improving of LD and CD solubility in acid solvent. OTFs containing LD and CD were prepared by solvent casting method using pullulan as polymeric material. Glycerin and ascorbic acid were used as a plasticizer and antioxidant, respectively. The OTF formulation was assessed according to various physico-mechanical properties. The OTF produced without glycerin was breakable whereas 5% and 10%w/w addition provided tackier film. However, small level of glycerin at 1% and 2%w/w were successfully applied to gain appropriate OTF. Although high pullulan content of 8 %w/w was remarkably showed acceptable film characteristic, loading content of both drugs was negligibly improved. Therefore, the developed OTFs that met the requirements was found to be composed of 8 %w/w of pullulan with either glycerin added of 1% or 2 %w/w of dry pullulan. When considering the stability of mentioned products, they were not exhibited appreciable stability as shown with the significant disappearing of LD and CD content during storage. Further formulation development should be conducted by pointing out with specific additives and method of preparation.