This presentation talks about the design and in vivo pharmacokinetic study of a newly developed lamivudine transdermal patch and lists the advanatages of this new formulation over the oral formulation of the drug.

1. Design and in vivo pharmacokinetic study of a
newly developed lamivudine transdermal
patch
Project by
Sriram Alluru
Pharmaceutical Engineering and Science
Department of Chemical and Biochemical Engineering
Rutgers, The State University of New Jersey
April 16th, 2020

2. Aim:-
➢ To formulate a matrix-type transdermal patch as an attempt to deliver LAM transdermally to overcome the problems
that are associated with the short biological half life.
➢ To develop an appropriate formulation for the transdermal patch.
Introduction:-
➢ Lamivudine (LAM) is an antiretroviral drug for treatment of Acquired immunodeficiency syndrome (AIDS) and
Hepatitis B Virus (HBV).
➢ Although, the bioavailability of orally administered form is suitable, major limitations of the current treatment are
related to the short biological half-life.

3. ➢ Three polymers were selected for the preparation of the drug supply layers of
the patches-
• Methyl Cellulose (MC) -(neutral)
• Sodium Alginate (SA) -(anionic)
• Chitosan (CS) -(cationic)
➢ Moreover, a hydrophilic polymer, is frequently responsible for the formation of a
water-permeable and easily hydrated film.
https://www.semanticscholar.org/paper/Formulation-and-
Evaluation-of-Repaclinide-Patch-
Natarajan/5d5c19294fc3e6705c24cd0a6613576ea728eda9
https://www.apotheken-
umschau.de/Verhuetung/Verhuetungspflaster-52286.html

4. Preparation of the placebo polymeric monolithic films:-
➢ Polymeric monolithic films are prepared by “solvent casting method”.
• Casting solvent of SA and MC was ethanol and distilled water mixture in ratio 1:2.
• 1% concentrated lactic acid aqueous solution was used as the casting solvent for CS.
➢ Plasticizers are added during the process to improve the brittleness of the polymer and to provide flexibility.
https://www.sciencedirect.com/science/article/pii/S2314724517301255

5. Drug-polymer compatibility studies:-
➢ The compatibility between the polymer and the drug was studied using the tests FT-IR and DSC.
➢ FT-IR result tell us that there are neither major shifts nor loss of functional peaks in the spectra of the polymeric films
containing drug.
➢ The result of DSC show us that there are slight changes in peak temperature and peak shape, which might be due to
dilution effect of polymers as well as thermal energy supplied during DSC scan.
https://www.sciencedirect.com/science/article/pii/S2314724517301255
FT-IR result DSC result

6. Physiochemical evaluation of the medicated films:-
➢ The thickness of the prepared films was measured using a micrometer.
➢ Drug content uniformity was measured for multiple patches spectrophotometrically using Spectro UV-VIS double beam
spectrophotometer.
➢ Surface pH was measured just to check if the patch was causing any type of irritation, edema, redness, etc., on the skin.
https://www.sciencedirect.com/science/article/pii/S2314724517301255

7. Ex vivo permeation study:-
➢ The permeation experiment was carried out using modified ‘Franz diffusion
cell’. Albino male rabbit’s skin is used for the analysis.
➢ The skin samples were mounted on the donor half-cells, so that SC (stratum
corneum) side was towards the donor and the dermal side was facing the
receptor compartment.
http://www.biogoods.com/products_bio/fabu/SupplyItem1547374280406.
html

8. ➢ The permeability coefficient was 10.76 ± 5.87 cm/min for FA. Significantly higher ‘P’ of 13.67 ± 6.06 and 16.76 ± 2.27
cm/min were achieved by FB and FC respectively.
➢ Similarly, FB and FC achieved significantly higher steady state flux (Jss) of 683.4 ± 30.3 and 837.9 ± 113.5 mg cm-2 min-1
respectively.
➢ The permeation data of the tested patches could be arranged as the following: MC patches > CS patches > SA patches.
https://www.sciencedirect.com/science/article/pii/
S2314724517301255
https://www.sciencedirect.com/scienc
e/article/pii/S2314724517301255

9. In vivo pharmacokinetic study:-
➢ Male Sprague-Dawley rats were used in this study. The rats were divided into two groups (n=6 for each group).
➢ The animals of the first group (oral solution group) received oral solution of LAM while the second group animals (MC
transdermal patch group).
➢ Blood samples were collected post oral dose and transdermal patch application. The blood samples were centrifuged at
5000 rpm for 10 min and the separated plasma samples were assayed by a reported HPLC method.
https://www.sciencedirect.com/science/article/pii/S2314724517301255

10. ➢ A graph was plotted for ‘mean plasma concentration’ versus ‘time’, this shows the concentration profile
➢ The area under curve (AUC) for the orally administered dose was 16.91 ± 12.17 (μg*h)/ml
➢ The area under curve for a transdermal patch was observed to be 54.04 ± 13.18 (μg*h)/ml
https://www.sciencedirect.com/science/article/pii/S2314724517301255
https://www.sciencedirect.com/science/article/pii/S2314724517301255
➢ Frel % value of 74.07% suggested enhanced and
adequate pharmacological effect.

11. Advantages of transdermal patch:-
➢ Transdermal drug delivery system of LAM that could penetrate rat skin and reach the blood circulation for about 6 days.
➢ The biological half-life of LAM when delivered through a transdermal system was increased by 40 folds.
➢ Hence, toxicity caused by fluctuations and multi-doses can be controlled.
➢ No lag time was observed for the transdermal drug delivery system.
Alternative for the transdermal patch:-
➢ Controlled release tablet was formulated and analyzed which had a t1/2 of 9.08 hours.

12. Thank you!