Kalpesh Patel

Tyrosine kinase inhibitors treat chronic myeloid leukemia but have many negative effects. These BCS Class II or IV medicines have low oral bioavailability due to poor solubility, permeability, or both. As P-glycoprotein substrates and hepatic presystemic metabolism inactivators, these medicines have another drawback. The present work sought to overcome the limitations of tyrosine kinase inhibitor bosutinib. A transdermal system with the medication put into a SMEDDS was created. The investigation began with solubility and emulsification studies to choose the proper oil (oleic acid), surfactant (Tween 20), and cosurfactant (Transcutol® P). The microemulsion zone was identified using ternary phase diagrams. The resultant SMEDDS exhibited a narrow polydispersity index and a droplet size of 45.66 ± 2.4 nm. The formulation's zeta potential prevented aggregation during storage, as shown by thermodynamic stability investigations under physical and thermal stress. Dispersibility and dilution experiments showed that the formulation formed the microemulsion instantly in vivo. BOS-loaded liquid SMEDDS was gelled with 2% HPMC K15M to make G-SNEDDS. The liquid SMEDDS and G-SMEDDS had similar properties. In vitro dissolution showed that near to 100% drug release could be achieved in 30 mins, compared to 5–6% for the simple medication. The formulation's in vitro permeability testing employing an artificial membrane demonstrated a 2.18-fold increase in drug penetration compared to the basic drug suspension.

Tyrosine kinase inhibitors have shown to be effective in the treatment of chronic myeloid leukemia. These drugs generally belong to the Biopharmaceutical Classification System Class II or IV, indicating that their oral bioavailability is less due to its poor solubility, permeability, or both. Dasatinib is a tyrosine kinase inhibitor and the present study was aimed to overcome these limitations associated with it. Thus, a transdermal system comprising of the drug loaded into a self-microemulsifying drug delivery system was formulated. The study started by selecting the right combination of the oil (oleic acid), surfactant (Labrasol®), and cosurfactant (polyethylene glycol 400) by performing solubility and emulsification ability studies. The ternary phase diagrams were constructed to identify the microemulsion region. The liquid system was converted into an easy-to-handle gel form using 1% w/w Carbopol ETD 2020 as the gelling agent. The final system had a droplet size of 76.42 ± 1.2 nm, a narrow polydispersity index, and a high zeta potential. The thermodynamic stability studies, dispersibility and dilution tests proved that the formulation would be unaffected and would form the microemulsion instantaneously. In vitro dissolution confirmed close to 100% drug release could be obtained within 30 mins as opposed to the plain drug showing only 50 – 60 % release. In vitro permeability studies, revealed a 1.6-times enhancement in the permeation of the drug. Preparation of a self-microemulsifying drug delivery system and loading it into a topical gel could address the issues associated with the effective delivery of dasatinib.