Pavendra Transdermal Delivery Patch System

presentation on preparation of transdermal delivery patch

1. Preparation of transdermal patches of leave extract of Calotropis gigantea in the management of Rheumatoid Arthritis By Pavendra

2. Introduction Transdermal drug delivery (TDD) is defined as self-contained, discrete dosage forms which, when applied to the intact skin, deliver the drug, through the skin at controlled rate to the systemic circulation. Most common TDD dosage forms are patches. It allows continuous input of drugs with short biological half-lives and eliminates pulsed entry into systemic circulation Improves bioavailability of drug by avoiding its first pass metabolism It has improved patient compliance

3. Limitations Cost is high. TDDS cannot deliver ionic drugs Cannot develop TDDS for drugs of large molecular size. TDDS cannot deliver drugs in a pulsatile fashion. Cannot develop TDDS, if drug or formulation causes irritation to skin.

4. Different shapes of Marketed Transdermal patches

5. Types of transdermal patches Single-layer drug-in-adhesive – in this the medicine is included right inside the skin-contacting glue with a single backing film . Multi-layer drug-in-adhesive – consist of more than drug-in-adhesive layers underneath a single backing film separated by layers. Reservoir – consists of a drug containing liquid compartment separated from the release liner by a semi-permeable membrane and adhesive. Matrix – consist of a semisolid drug containing matrix in direct contact with the release liner. Vapour patch - adhesive layer not only serves to adhere but also to release vapour . Mainly used to release essential oils

6. Basic Components of TDDS Polymer matrix/ Drug reservoir Drug Permeation enhancers Adhesive Backing laminates Release liner Other excipients like plasticizers, solvents

7. Selection of Drug for TDDS TDDS is more suitable for drugs having : Extensive first pass metabolism Marrow therapeutic window Short half life and more frequent dosing Low molecular weight Adequate solubility in oil and water ( logP ~ 1 to 3) Low melting point (<200 degree C)

8. Solvent Casting Method for TDDS Preparation

9. What is rheumatoid arthritis? Rheumatoid arthritis is an autoimmune disease where the body’s immune system attacks its own tissues. Rheumatoid arthritis can affect anyone at any age, and may cause significant pain and disability.

10. Symptoms of Rheumatoid Arthritis Tender ,warm ,swollen joints joint stiffness that is usually worse in the mornings and after inactivity Fatigue, fever and loss of appetite

11. Pathogenesis of Rheumatoid Arthritis

12. PLANT PROFILE of CALOTROPIS GIGANTEA Taxonomical classification • Kingdom: Plantae • Division: Magnoliophyte • Class: Magnoliopsida • Order: Gentian ales • Family: Apocynaceae • Genus: Calotropis • Species: C. gigantean

13. Chemical constituents of CALOTROPIS GIGANTEA Leaves - contain mainly the amyrin , amyrin acetate, ß- sitosterol , urosolic acid, cardenolides , calotropin , calotropagenin Latex - contains caoutchouc , calotropin , calotoxin 0.15%, calactin 0.15%, uscharin 0.45%, trypsin, voruscharin , uzarigenin , syriogenin and proceroside • Class: Magnoliopsida Flower - contains the flavonoids, queretin - 3- ratinoside , sterol, calactin , calotoxin , calotropagenin , calotropin , polysaccharides with D-arabinose, glucose, glucosamine and L- rhamnose • Family: Apocynaceae B ark - contains triterpenes, a new norditerpenyl ester, named Calotropterpenyl ester, and two pentacyclic triterpenoids, namely calotropursenyl acetate and calotropfriedelenyl acetate, akundarol isovalerate , mundarol isovalerate and quercetin -3- rutinoside

14. Aim The main purpose of this transdermal patches of leave extract of Calotropis gigantea is to prolong the action of drug and used in the management of the rheumatoid arthritis. Transdermal patches give sustained and controlled release of drug so that the dose frequency of drug will reduce.

15. Objective To reveal the efficacy of Calotropis gigantea in treatment of arthritis. Perform both in-vitro and in-vivo study so as to support further clinical evaluation To find a better bioavailable alternate with higher efficacy for arthritis. To make transdermal patches of leaf extract of Calotropis gigantea

16. Material and Methadology Collection of Plant - leaves of Calotropis gigantean were collected from the surrounding areas of Raipur in Chhattisgarh state and were authenticated by department Head. Extraction - soxhlet extraction with petroleum ether 40-60, acetone and 70% ethanol (70:30 hydro-alcoholic). The solvents were evaporated using rotary evaporator to get semisolid extracts. Subsequently, the extracts were weighed and yield was calculated. Phytochemical Screening - Chemical tests were carried out on the all extracts using standard procedures to identify the constituents as described by Kokate et al. 2002.

17. In- vivo animal study Adult healthy Wistar rats of 7–8 weeks of age weighing between 150 and 200 g were selected. Animals were divided in 10 groups containing six animals in each. Acute oral toxicity studies - of Leaves of Calotropis gigantean extracts were carried out in Wistar rats using the limit test or main test (Up and down procedure) as per OECD guideline 425. Physical parameters - Paw volume, Ankle joint thickness, Grip strength, Body weight were measured Biochemical assessment - aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphates (ALP), blood urea and creatinine, estimation was done. Haematological assessment - red blood count (RBC), haemoglobin ( Hb ), total white blood cell count, and platelet counts were measured. Organ to body weight ratio

18. Formulation design

19. Evaluation of Transdermal patches Physicochemical parameters Gross visual appearance Scanning Electron Microscopy (SEM) Thickness Test Folding Test Uniformity of weight Moisture content Moisture uptake Drug-polymer interaction studies by FT-IR spectrophotometry In vitro diffusion studies Stability studies Skin Irritation test

20. Result And Discussion Extraction yield of Calotropis gigantea with various solvents

21. Qualitative phytochemical test of various extracts + = Positive, - = Negative; CGHY = Calotropis gigantea hydro-alcoholic extract CGAC = Calotropis gigantea acetone extract CGPE = Calotropis gigantea petroleum ether extract

22. Calculated LD 50 of the various extracts of Calotropis gigantea for Acute toxicity studies

23. Effect of Calotropis gigantea extracts on ankle joint diameter of CFA induced arthritic animals (Percentage inhibition)

24. Graphical Representation

25. Effect of Calotropis gigantea extracts on serum liver and kidney markers

26. Graphical Representation

27. Effect of Calotropis gigantea extracts on hematological parameters

28. Graphical Representation

29. Effect of Calotropis gigantea extracts on relative body organ weight ratio

30. Graphical Representation

31. Evaluation of TDDS of acetone extract of Calotropis gigantea Calotropis gigantea Transdermal Patches

32. Surface morphology by Scanning Electron Microscopy (SEM) Films showed uniform distribution of drug in the polymer matrix. The SEM of transdermal films of PVP: PG are 1000X and 1500X represented

33. Physicochemical Evaluation of Herbal Transdermal Patch

34. Moisture uptake values of films at two relative humidity values (75% and 95%)

35. FTIR study for drug polymer interaction FTIR spectra of pure C. gigantea acetone extract FTIR spectra of Transdermal patch mixture with drug

36. In–Vitro Drug Release Study of Prepared Transdermal Patch

37. Graphical Representation

38. Evaluated data of optimized formula after 6 months of Stability studies

39. Conclusion Present study's findings suggest that the studied extracts might be a practical and inexpensive way to get a good effective alternative for the treatment of arthritis.

40. References 1. A. Arunachalam , M. Karthikeyan . D Vinay Kumar, Pratap . M, S. Seetharaman , Ashutosh Kumar, S. Manidipa “Transdermal Drug Delivery System: A Review Current Pharma Research” Volume. 1, Issue 1, October-December 2010 2. Loyd V. Allen Jr, Nicholas G. Popovich, Howard C. Ansel. Pharmaceutical dosage forms and drug delivery systems, 8th Edition., Wolter Kluwer Publishers, New Delhi, 2005 3. Kumar P, Sankar C, Mishra B. Delivery of macromolecules through skin. The Indian Pharmacist 2004, 4. Kumar R, Philip A. Modified Transdermal Technologies: Breaking the Barriers of Drug Permeation via the Skin. Trop J Pharm Res. 2007, 5. Shingade GM et al, “review on: recent trend on transdermal drug delivery” Journal of Drug Delivery & Therapeutics; 2012. 6. Chien YW et al, Transdermal Controlled-Release Drug Administration, Novel Drug Delivery System: Fundamental Development concepts and Biochemical Applications. New York: Marcel Dekker; 1982. 7. Puttipipatkhachorn S. Journal of Controlled Release, 2001 8. Wilkosz MF. Transdermal Drug Delivery: Part I. U.S. Pharmacist. Jobson publication;2003. 9. Ramteke K.H. et al, “transdermal drug delivery system: a review” Journal of Advanced Scientific Research 2012, 10. Dhiman et al, transdermal patches: a recent approach to new drug delivery system International Journal of Pharmacy and Pharmaceutical Sciences Volume 3, 2011

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