Journal of Pharmaceutical Innovation

, Volume 14, Issue 4, pp 391–399 | Cite as

Response Surface Methodology for Optimization of Ultrasound-Assisted Transdermal Delivery and Skin Retention of Asenapine Maleate

  • Jyothsna Manikkath
  • Gautham G. Shenoy
  • Sureshwar Pandey
  • Srinivas MutalikEmail author
Original Article



Asenapine maleate (ASP) is an antipsychotic agent used in the treatment of schizophrenia and bipolar disorder. It has extremely low oral bioavailability of < 2%, necessitating the utilization of alternate route of administration. The objective of this work is to study and optimize the sonophoretic transdermal delivery and skin retention of ASP statistically, in Sprague-Dawley rat skin, using response surface methodology in Design of Experiments (DoE).


I-optimal design was employed, using the ultrasound (US) parameters viz., duration of US application, amplitude of US, and mode of US application (simultaneous application or pretreatment) as the input variables. Steady-state flux (Jss) of ASP and amount of drug retained in skin after 24 h was taken as the output responses.


The model and dependent variables were found to be significant and representative of the data and response surface. While passive diffusion yielded Jss of 2.575 μg/cm2/h, the same values with US application ranged from 8.18 to 127.68 μg/cm2/h. Passive diffusion of drug showed 46.22 ± 5.2 μg/cm2 of ASP retained in 24 h, while US application resulted in 99.07 to 1495.6 μg/cm2 of drug retained in skin in 24 h. Based on the findings from optimization studies, 30 min of US application, with amplitude of 27–28, and simultaneous application mode was found to achieve the optimal transdermal drug flux, with slightly lower retention values in skin.


The study found that the sonophoretic transdermal permeation and retention of ASP in vitro could be optimized using response surface methodology.


Asenapine maleate Transdermal Ultrasound Sonophoresis Design of Experiments Response surface methodology 



The authors are thankful to Orbicular Pharmaceutical Technologies Pvt. Ltd., Hyderabad, India for the gift sample of asenapine maleate, and to Manipal Academy of Higher Education, Manipal, India, for providing the facilities required to conduct the research work.

Compliance with Ethical Standards

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jyothsna Manikkath
    • 1
  • Gautham G. Shenoy
    • 2
  • Sureshwar Pandey
    • 3
  • Srinivas Mutalik
    • 1
    Email author
  1. 1.Department of Pharmaceutics, Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalIndia
  2. 2.Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical SciencesManipal Academy of Higher EducationManipalIndia
  3. 3.School of Pharmacy, Faculty of Medical SciencesThe University of West IndiesSt AugustineTrinidad and Tobago

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