1. PATCHES TRANSDERMAL DRUG DELIVERY
Lecturer: ass. prof. Beley N.N.

2. Plasters or patches (Emplastra)
are dosage form for external use, which sticks to the skin, affects on the skin, subcutaneous tissue and, in some cases, makes the overall effect on the body.
At room temperature patches look like a solid mass.

3. At room temperature emplastic mass is dense, but on the skin human it becomes soft and sticky.
When the temperature increases further patches begin to melt, turning into a dens liquid.
For convenience, the patches are applied over the fabric or paper.

4. Classification of patches depend on action and using
1. Epidermatical patches
2. Endermatical patches
3. Diadermatical (transdermal) patches

5. Epidermatical adhesive plasters don’t include medicine substances
and they are used:
to protect any part of the skin from harmful influences;
to close the skin defects;
for bring together the wound edges;
for fixing the bandages on the skin surface.
They must be sufficiently sticky, firmly to stick to the skin and not irritate it.

6. Endermatical adhesive plasters
They include drugs that have therapeutic effect on patient skin.
This type of patches acts only on the external layer of the skin (antiseptic action).

7. Diadermatical (transdermal) adhesive plasters
They include medicines substances and have special structure that ensures drug penetration through the skin.
Medicines substances can penetrate into deeper layers of the skin or have a general effect on the body.

8. Transdermal patches are flexible pharmaceutical preparations of varying sizes, containing one or more active substances.
They are intended to be applied to the unbroken skin in order to deliver the active substance(s) to the systemic circulation after passing through the skin barrier.

9. Dermal and transdermal drug delivery
Patches for dermatological drug therapy are intended to produce desired therapeutic action at specific sites in the epidermal tissue .
A drug′s ability to penetrate the skins epidermis, dermis, and subcutaneous fat layers will lead to transdermal (percutaneous) drug delivery giving rise to systemic action .
Therefore, the extent the drug can travel through the different skin layers determine the delivery system.

10. Advantages of the Transdermal drug delivery
- Avoiding hepatic first pass effect
- Continuous drug delivery
- Fewer side effect
- Therapy can be terminated at any time
- Improved patient compliances

11. Disadvantages of the Transdermal drug delivery:
Cosmetically non-appealing
- May display irregular absorption

12. The fraction of the drug that penetrate the skin via any route depends on:
1. The physicochemical nature of the drug, specially its size, solubility and partition coefficient.
2. The site and condition of the skin.
3. The formulation.
4. How vehicle component temporarily change the properties of the stratum corneum.

13. Ideal molecular properties for drug penetration
- A low molecular weight (generally less than 500 Daltons)
- An adequate solubility in oil and water
- A balanced partition coefficient
- A low melting point
- Potent drug (maximum 50 mg/day)

14. Transdermal patches normally consist of an outer covering which supports a preparation which contains the active substance(s).
The transdermal patches are covered on the site of the release surface of the preparation by a protective liner, which is removed before applying the patch to the skin.

15. The outer covering is a backing sheet impermeable to the active substance(s) and normally impermeable to water, designed to support and protect the preparation.
The outer covering may have the same dimensions as the preparation or it may be larger.
In the latter case the overlapping border of the outer covering is covered by pressure-sensitive adhesive substances which assure the adhesion of the patch to the skin.

16. The patches contain the active substance(s) together with excipients such as stabilisers, solubilisers or substances intended to modify the release rate or to enhance transdermal absorption.

17. Application of the patches
When applied to the dried, clean and unbroken skin, the transdermal patch adheres firmly to the skin by gentle pressure of the hand or the fingers and can be peeled off without causing appreciable injury to the skin or detachment of the preparation from the outer covering.
The patch must not be irritant or sensitising to the skin, even after repeated applications.

18. The protective liner generally consists of a sheet
of plastic or metal material.
When removed, the protective liner does not detach the preparation (matrix or reservoir) or the adhesive from the patch.
Transdermal patches are normally individually enclosed in sealed sachets.

19. Classification of the adhesive plasters
1. Depend on the composition:
ordinary
rubber,
2. Depend on the technique:
patches as the mass
smeared patches

20. Classification of the ordinary patches:
Depending on the substances that are prevalent in emplastic base:
lead (Diachylon),
Lead-pitch,
Lead-wax,
Pitch-wax patches.

21. Patches are produced in the follow forms:
1. Viscose mass on the liner (fabric, paper … )
2. Solid patches mass (cylinders, rods, bars, sticks)
3. Liquid (skin glue)
4. Foam
5. Films

22. Composition of the diachylon
Sunflower oil parts,
Fat purified parts
Lead oxide parts
Water in sufficient quantity.

23. Stages of obtaining simple diachylon:
1. Melting oil and fat
2. Shredding litharge
3. Sifting litharge
4. Mixing litharge with fresh boiling water clean
5. Mixing suspensions of Pb oxide with alloy of oil and fat
6. Production patches mass
7. Flushing ready mass from glycerol
8. Drying patches

24. Technology of the simple diachylon:
In the boiling process, which lasts for 1/2-2 hours, the original red mixture gradually turns into a whitish-gray, and at the end of boiling - to whitish.
In this case, the saponification reaction occurs, resulting in the formation fatty acid salt of lead (lead soap).
Consequently, it is chemically diachylon is a mixture of lead salts of oleic, palmitic and stearic acids with a significant predominance of the former.

25. Boiling patch is considered complete when a small sample at pouring it into cold water, gives a plastic mass which at the kneading does not stick to your fingers.
Then, patch is washed off from glycerol.

26. Ready emplastic mass is rolled out to form sticks, which enveloping parchment or waxed paper.
Diachylon itself has no use, but its part are used to many patches and certain ointments production.

27. Elastic patches Natural rubber - 25,7 pm Rosin - 20.35 pm
Composition:
Natural rubber ,7 pm
Rosin pm
Zinc oxide pm
Lanolin anhydrous ,9 pm
Liquid paraffin ,3 pm
Neozonu D ,75 pm

28. Diachylon simple 85 parts,
Hard-lead (Emplastrum plumbi compositum) - is an alloy of diachylon with resinous substances.
Composition:
Diachylon simple parts,
Rosin parts,
Turpentine parts.
Diachylon and rosin are melted in a boiler with a steam heating. After that, the turpentine is added, mixed thoroughly and mass is rolled out or form sticks.
Used as a mild irritant.

29. Lead-wax patches
Bases in these patches are simple alloys diachylon with beeswax and lanolin:
Mercury Patch (Ernplastrum hydrargyri)
Epilinovy patch (Ernplastrum epilini)
Akrihinovy patch (Ernplastrum acrichini)

30. Corn patches is a homogeneous soft, sticky, but the discrepancy mass yellow or dark yellow. The melting point is above 60 ° C.
Composition:
Salicylic acid parts,
Rosin parts,
Paraffin parts,
Petrolatum parts.
Wax, rosin and petroleum jelly are loaded in the reactor to alloy with stirring, then salicylic acid is dissolved, and the obtained mass poured into molds to 3 g.

31. Rubber (caoutchouc) plaster Adhesive tape (Emplastrum adhaesivum elasticum externum)
Composition:
Rosin parts
Yellow wax parts
Zinc oxide parts
Anhydrous lanolin parts
Rubber parts
Gasoline parts

32. Stages of the Adhesive tape production
1. Preparation of rubber glue (dissolution of rosin and rubber in gasoline)
2. Obtaining the mix of substances that prevent aging (homogenization mixture of lanolin protystarytelem)
3. Preparation of zinc base (homogenization mixture lanolin, beeswax and zinc oxide)
4. Mixing rubber adhesives, pastes and zinc substances that prevent aging basis (6 hours)
5. Put plasters mass on a moving belt machines for plastering of the mass (shpredinh)

33. Machine for smearing of the plasters mass on the tape from fabric

34. Pepper Patch (Emplastrum capsici)
Composition:
Soft extract of capsicum
(obtained specifically for the patch) ,0 %
Soft extracts of belladonna ,3 %
Tinctures Aralias ,3 %
They are produced in the form of rectangular pieces of paper size 12X18, 10x18 cm and 8X18, in each package are located on two pairs of pieces that ran in cellophane.

35. Bactericidal patches (Emplastrum adhacsivum bactericidum)
which consists of a gauze pad soaked in antiseptic solution, which contain:
Frc %
Sintomitsina ,08 %
Brilliant green in 40% alcohol ,01%

36. Skin glue or liquid adhesives (Emplastra Liquida)
Skin glue - liquid, which forms adhesive elastic strong film at the skin after evaporation of the solvent.
Skin adhesives are otherwise called liquid adhesives, and relatively widely used as epidermatical and endermatical patches.
Most often emplastic film is formed by substances such as collodion, rosin or synthetic.
To provide greater flexibility to the mixture vegetable oils are added.

37. Mustard
are rectangular sheets of paper size 8X12, 5 cm, coated on one side of a layer of powder defatted mustard seeds thickness 0,3-0,55 mm.
Raw materials are seeds Sarepts (Semina sinapis junceae) and Black (Semina sinapis nigrae) mustard.

38. From the resulting skim powder cake mustard paste is prepared by mixing it with a solution of rubber in gasoline.
Smearing is produced by emplastic machine.

39. Stages of the mustard production:
1) preparation of glue;
2) preparation of mustard mass;
3) smearing of the mass on the paper, drying of cutting roll and laying mustard patches to the feet;
4) packing;
5) the recovery of gasoline.