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DIFFUSION STUDIES IN TANSDERMAL DRUG DELIVERY SYSTEM

DIFFUSION STUDIES IN TANSDERMAL DRUG DELIVERY SYSTEM. DIFFUSION. Movement of molecules from an area of high concentration to area of low concentration. Movement from one side of membrane to other side. Diffusion is time dependent process.

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DIFFUSION STUDIES IN TANSDERMAL DRUG DELIVERY SYSTEM

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  1. DIFFUSION STUDIES IN TANSDERMAL DRUG DELIVERY SYSTEM

  2. DIFFUSION • Movement of molecules from an area of high concentration to area of low concentration. • Movement from one side of membrane to other side. • Diffusion is time dependent process. • Movement is based on kinetic energy(speed),charge and mass of molecules. • diffusion of polar drugs is much faster than viable tissue than across stratum corneum.

  3. Fick’s First Law of Diffusion Percutaneous absorption of most drugs is a passive-diffusion process that can be described by Fick’s first law of diffusion dQ/dt = JT = PAΔC • JT is the total flux transported through a unit area of skin per unit time in steady state (µg/hr) • A is area of the skin • P is the effective permeability coefficient • ΔC is the drug concentration gradient across the skin

  4. The Structure of Human Skin

  5. SKIN • Skin is the most intensive and readily accessible organ of the body as only a fraction of millimeter of tissue separates its surface from the underlying capillary network. • Skin has been used for centuries for administration of drugs for local treatment, but recently it has been used as a pathway for systemic drug delivery. • The barrier function of skin prevents both water loss and entrance of external agents. • Transdermal route is through the skin is of particular interest for drugs that have a systemic short elimination half life or undergo extensive first pass metabolism.

  6. The various steps involved in transport of drug from patch to systemic circulat are as follows: Diffusion of drug from drug reservoir to the rate controlling membrane. Diffusion of drug from rate limiting membrane to stratum corneum. Sorption by stratum corneum and penetration throughviable epidermis. Uptake of drug by capillary network in the dermal papillary layer. Effect on target organ.

  7. TRANSDERMAL DRUG DELIVERY SYSTEM (TDDS) • Transdermal drug delivery systems (TDDS), also known as ‘‘patches,’’ are dosage forms designed to deliver a therapeutically effective amount of drug across a patient’s skin .

  8. Properties of the drug to be formulate into TDS: • The drug dose should be less than 10 mg. • The molecular weight of the drug should less than 1000 daltons. • Drug must be hydrophobic in nature. • Types of transdermal systems. • Matrix control drug delivey systems • Microsealed control drug delivey systems • Matrix diffusion control drug delivey systems

  9. Advantages of transdermal delivery system • The system avoids the chemically hostile GI environment • No GI distress or other physiological contraindications of the oral route • Can provide adequate absorption of certain drugs • Increased patient compliance • Avoids first-pass effect • Allows effective use of drugs with short biological half-life • Provides controlled plasma levels of very potent drugs

  10. Disadvantages of TDS • Drug that require high blood levels cannot be administered • Adhesive may not adhere well to all types of skin • Drug or drug formulation may cause skin irritation or sensitization • Uncomfortable to wear • May not be economical

  11. TRANSDERMAL ADMNISTRATION • To study the percutanious transfer o drugs the skin can be considered as a bilaminate membrane consisting of stratum corneum (lipophilic layer) and the living tissue (hydrophilic layer)that comprises granular and basal layers of the epidermis and the dermis. • Permeability coefficient through the skin P can be expressed as P= permeability cofficient . k= Partition coefficient Lv ,Ls = diffusion pathlenghts Dv ,ds = diffusion coefficients S,v = stratum corneum and viable tissue

  12. If the drug diffuses slowly through the stratum corneumklvDs is much less than lsDvand the equation becomes This case skin permeability is controlled by stratum corneum alone. • The diffusion through the stratum corneum is fast, klvds is much greater than lsdv and te equation becomes • the partition coefficient may be influenced in the permeability.

  13. TOJO’S BRICK MODEL

  14. Tojo proposed a random brick model for the transfer of drugs across the stratum corneum. • According to this model the transfer of drug is divided into 3 parallel pathways • a) across the cellular – inter cellular regions in series. • b)across the lipid inter cellular spaces • C) across the thin lipid layer sandwiched between flattened protein cells of the stratum corneum.

  15. Briks model equation is Deff= 2ε(1- ε) D1 + ε2 D2+ (1- ε)2 D3 By substituting d1,d2, d3 in the above equation ,it becomes the term n = volume fraction of lipids in the skin. K= lipid protein partition coefficient Dp & D1= diffusion coefficients And finally the flux across the skin is given by Cp = concentration of drug in protein cell layer h = thickness of the skin.

  16. In vitro drug diffusion studies • Usually, two types of diffusion cells are used • The Franz diffusion cell and • KesharyChien (K-C) diffusion cell • Diffusion cells generally comprise two compartments, one containing the active component (donor compartment) and the other containing receptor solution (receptor compartment), separated by barrier i.e. albino rate abdominal skin.

  17. Franz diffusion cell

  18. The donor compartment was open at the top and was exposed to atmosphere. • The temperature was maintained at 37 ±0.50c and receptor compartment was provided with sampling port. • The diffusion medium used was phosphate buffer (pH 7.4). • The diffusion studies were done to get an idea of permeation of drug through barrier from the transdermal system.

  19. The in vitro diffusion study was carried out with the abdominal rat skin using Franz diffusion cell. • The mice abdominal skin was placed on receptor compartment and both compartments held tight by clamps. • Phosphate buffer pH 7.4 was used as receptor solution. • The volume of diffusion cell was 15 ml and stirred with bent stainless steel pin. • The temperature was maintained at 37 ± 0.5°C with the help of magnetic stirrer.

  20. The diffusion was carried out for 24 hours and 1 ml sample was withdrawn at an interval of 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hour. • The same volume of phosphate buffer pH 7.4 was added to receptor compartment to maintain sink conditions and the samples were analyzed at 220nm in UV spectrophotometer.

  21. CONCLUSION • Diffusion helps in developing so many drug delivery systems especially controlled &sustain drug delivery systems. • Diffusion helps in understanding pharmacokinetic parameters of drug. • Diffusion helps in many bioavailability studies.

  22. BIBLOGRAPHY • WWW.GOOGLE.COM • WWW.WIKIPEDIA.COM • MARTIN TEXT BOOKS. • www.googleimage.com

  23. THANK YOU

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