Transdermal drug delivery system sonam


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Transdermal drug delivery system sonam

  2. 2. There are main four types of TDDS 1) Membrane moderated system. 2) Adhesive diffusion controlled system. 3) Matrix dispersion system. 4) Micro reservoir system. 2
  3. 3.  In this system, the drug reservoir is totally encapsulated in a shallow compartment molded from a drug impermeable metallic plastic laminate and a rate controlling polymeric membrane. In the drug reservoir compartment, the drug solids are either dispersed in a solid polymeric matrix or suspended in an unleachable, viscous liquid medium, eg: ethylene-vinyl acetate copolymer. 3
  4. 4. Rate controllingpolymeric membrane Drug reservoir Drug-impermeable Metallic plastic laminate Adhesive Layer 4
  5. 5.  Theintrinsic rate of drug release from this type of drug delivery system is defined by dq/dt = Cr 1/Pm+1/Pa where Cr=drug concentration in reservior compartment Pm & Pa=permeability co-efficients of adhesive layer and rate controlling membrane 5
  6. 6. Adhesive layer Drug impermeable metallic plastic laminate ……………………..Rate controlling adhesive layer Drug reservoir 6
  7. 7.  It is a simplified version of the membrane moderated drug delivery system . Instead of completely encapsulating drug reservoir in a compartment fabricated from a drug impermeable metallic plastic backing. In this system the drug reservoir is formulated by directly dispersing the drug in an adhesive polymer and than spreading the medicated adhesive, by solvent casting onto a flat sheet of drug impermeable metallic plastic sheet backing to form a thin drug reservoir layer . Eg: verapamil TDDS – Once a day The release rate is given by dq/dt=(Ka/r x Da) Cr 7
  8. 8.  In this the drug reservior is formed by homogeneously dispersing the drug solids in a hydrophilic or lipophilic polymer matrix and the medicated polymer in then molded into medicated disc with a defined surface area and controlled thickness. This drug reservoir contaning polymer disc is then glued onto an occlusive baseplate in a compartment fabricated from a drug impermeable plastic backing. The release rate is defined by dq/dt=(ACp x Dp)½ 2t Where A= initial drug loading dose in polymer. Cp&Dp=drug concentration in polymer and drug diffusion from polymer . 8
  9. 9. Absorbent padOcclusive baseplate Impermeable backingAdhesive rim Drug reservoir 9
  10. 10.  MATRIX DISPERSION TYPE TDDS Eg: nicotine copolymer matrix type tdds 10
  11. 11. Occlusive base plate adhesive foam pad adhesive rim microscopic drug reservoir polymeric matrix (silicone elastomer) 11
  12. 12.  In this system both reservoir and matrix dispersion type combination is used. The drug reservoir is formed by first suspending the solid drug in aqueous solution of water soluble polymer and than dispersing homogenously the drug suspension in a lipophlilic polymer by high shear mechanical force to form thousands of unleachable , microscopic spheres of drug reservoirs , than stabilized by cross linking the polymer chain , so formed medicated disc is positioned at center of the aluminium backing and is surrouneded by adhesive rim. 12
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  15. 15.  Transdermal drug delivery system is evaluated using a two compartment diffusion cell assembly under identical conditions. The evaluation is necessary for screening and measuring fluxes, partition co-efficient and diffusion co-efficient. The evaluation is performed by 1) In-vitro method A) In-vitro drug release kinetics. B) In-vitro skin permeation kinetics. 2) In-vivo method. 15
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  17. 17.  Two compartment diffusion cell assembly under identical condition is done by mounting a skin specimen excised from either human cavander or a live animal on a vertical diffusion cell such as franz diffusion cell and other one is horizontal diffusion cell such as vilia-chien skin permeation cell. Each unit of the TDDS is then applied with its drug releasing surface in intimate contact with the stratum corneum surface of the skin. The skin permeation profile of the drug is followed by sampling the receptor solution at predetermined intervals untill steady state flux is established and assay drug concentration in the sample by a sensitive analytic method . Such as HPLC . 17
  18. 18.  Using franz diffusion cell assembly, the mechanism and the rate of drug release of different TDDS where evaluated and compared. The results indicated that nitroglyrerin is released at a constant rate profile from TDDS like the transderm nitro system(a polymer membrane permeation controlled TDDS) and the deponit system (a drug reservior controlled TDDS). The release rate from of nitro glycerine from transderm nitro system (0.843 0.035 mg /cm2/day) is almost three times greater than that from the deponit system (0.324 0.011 mg /cm2/day) . This suggest that diffusion through the rate controlling adhesive polymer matrix in it the deponit system play a greater rate limiting role over the release of nitroglycerine than does permeation through the rate controlling polymeric membrane in the transderm nitro system. 18
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  22. 22.  1) Animal skin model The skin permeation studies of this TDDS suggest that all four system give a constant rate of skin permeation as shown in figure. The highest rate of skin permeation was observed with the nitrodsic system (0.426 0.024 mg /cm2/day) which is how ever statistically no different from the rate of skin permeation for nitroglycerine (0.476 0.041 mg /cm2/day). A comparision made between the rate of skin permeation and the rate of drug release suggest that under sink condition all TDDS deliver nitroglycerine at a greater than its rate of permeation across the skin ( Rd > Ra ). This phenomenon is an indication that the stratum corneum play a rate limiting role in the transdermal delivery of drugs. eg: Transderm nitro and depoit system. 22
  23. 23.  2) Human cadaver skin model. This system is used to investigate for various nitroglycerine releasing TDDS using valia chien skin permeation cell. it as been found that difference in the type and thickness of a skin specimen and variation in the hydrodynamics of invitro skin permeation cells could affect intraspecies corelation in the skin permeation rates. eg: the skin permeation rates of progesterone and its hydroxy derivatives across human cadaver skin. 23
  24. 24.  In transdermal bioavailability of nitroglycerine resulting from the 24-32 hr topical application of TDDS system in in human volunteers as shown in figure 24
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  26. 26. T hanku 26