CONTEXT: Asenapine maleate (ASPM) is an antipsychotic drug for the treatment of schizophrenia and bipolar disorder. Extensive metabolism makes the oral route inconvenient for ASPM. OBJECTIVE: The objective of this study is to increase ASPM bioavailability via transdermal route by improving the skin permeation using combined strategy of chemical and nano-carrier (transfersomal) based approaches. MATERIALS AND METHODS: Transfersomes were prepared by the thin film hydration method using soy-phosphatidylcholine (SPC) and sodium deoxycholate (SDC). Transfersomes were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, and in vitro skin permeation studies. Various chemical enhancers were screened for skin permeation enhancement of ASPM. Optimized transfersomes were incorporated into a gel base containing suitable chemical enhancer for efficient transdermal delivery. In vivo pharmacokinetic study was performed in rats to assess bioavailability by transdermal route against oral administration. RESULTS AND DISCUSSION: Optimized transfersomes with drug:SPC:SDC weight ratio of 5:75:10 were spherical with an average size of 126.0 nm, PDI of 0.232, ZP of -43.7 mV, and entrapment efficiency of 54.96%. Ethanol (20% v/v) showed greater skin permeation enhancement. The cumulative amount of ASPM permeated after 24 h (Q24) by individual effect of ethanol and transfersome, and in combination was found to be 160.0, 132.9, and 309.3 μg, respectively, indicating beneficial synergistic effect of combined approach. In vivo pharmacokinetic study revealed significant (p < 0.05) increase in bioavailability upon transdermal application compared with oral route. CONCLUSION: Dual strategy of permeation enhancement was successful in increasing the transdermal permeation and bioavailability of ASPM.
CONTEXT: Asenapine maleate (ASPM) is an antipsychotic drug for the treatment of schizophrenia and bipolar disorder. Extensive metabolism makes the oral route inconvenient for ASPM. OBJECTIVE: The objective of this study is to increase ASPM bioavailability via transdermal route by improving the skin permeation using combined strategy of chemical and nano-carrier (transfersomal) based approaches. MATERIALS AND METHODS: Transfersomes were prepared by the thin film hydration method using soy-phosphatidylcholine (SPC) and sodium deoxycholate (SDC). Transfersomes were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, and in vitro skin permeation studies. Various chemical enhancers were screened for skin permeation enhancement of ASPM. Optimized transfersomes were incorporated into a gel base containing suitable chemical enhancer for efficient transdermal delivery. In vivo pharmacokinetic study was performed in rats to assess bioavailability by transdermal route against oral administration. RESULTS AND DISCUSSION: Optimized transfersomes with drug:SPC:SDC weight ratio of 5:75:10 were spherical with an average size of 126.0 nm, PDI of 0.232, ZP of -43.7 mV, and entrapment efficiency of 54.96%. Ethanol (20% v/v) showed greater skin permeation enhancement. The cumulative amount of ASPM permeated after 24 h (Q24) by individual effect of ethanol and transfersome, and in combination was found to be 160.0, 132.9, and 309.3 μg, respectively, indicating beneficial synergistic effect of combined approach. In vivo pharmacokinetic study revealed significant (p < 0.05) increase in bioavailability upon transdermal application compared with oral route. CONCLUSION: Dual strategy of permeation enhancement was successful in increasing the transdermal permeation and bioavailability of ASPM.
Authors: Yana Zorkina; Olga Abramova; Valeriya Ushakova; Anna Morozova; Eugene Zubkov; Marat Valikhov; Pavel Melnikov; Alexander Majouga; Vladimir Chekhonin Journal: Molecules Date: 2020-11-13 Impact factor: 4.411