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Edit Comment Close Premium member Presentation Transcript WELCOME: WELCOME 4/10/2011 1 vikramjit singhEvaluation of Transdermal Drug Delivery System by In-Vitro Method: Evaluation of Transdermal Drug Delivery System by In-Vitro Method PRESENTED BY…. Vikramjit Singh 1 ST SEM. M.PHARM DEPARTMENT OF PHARMACEUTIC S 4/10/2011 2 vikramjit singhCONTENTS: CONTENTS 4/10/2011 3 Introduction Evaluation of adhesives In-vitro drug release studies In-vitro skin permeation studies Conclusion Reference vikramjit singhINTRODUCTION: INTRODUCTION Transdermal therapeutic systems are defined as self-contained, discrete dosage forms which, when applied to the intact skin, deliver the drug(s), through the skin, at a controlled rate to the systemic circulation. It provide a means for non invasive, continuous administration of various types of drugs. When skin is use as a port for the entry of drug, a Transdermal therapeutic system can delivery medications to the systemic circulation more conveniently and effectively than can currently available dosage forms. 4/10/2011 4 vikramjit singhSlide 5: Transdermal drug delivery system requires systemic evaluation at various stages of its development. These evaluation tests are described below: Evaluation of adhesive In vitro dissolution studies for drug release and skin permeation studies 4/10/2011 5 vikramjit singhEVALUATION OF ADHESIVE: EVALUATION OF ADHESIVE 4/10/2011 6 Pressure sensitive adhesives can be evaluated on the basis of their three basic properties : Peel adhesion properties Tack properties Shear strength properties For the evaluation of adhesive properties, adhesive laminates are prepared, consisting of a backing sheet or membrane, an adhesive film and release liner. For the preparation of test laminate in laboratory transfer coating process is used vikramjit singhSlide 7: A schematic representation of this process Air or oven dry Apply backing membrane Press laminates Roller Finished laminates Release liner Adhesive material 4/10/2011 7 vikramjit singhPEEL ADHESIVE PROPERTIES: PEEL ADHESIVE PROPERTIES Peel adhesion is the force required to remove an adhesive coating from a test substrate. It is important in Transdermal devices because the adhesive should provide adequate contact of the device with the skin and should not damage the skin on removal. 4/10/2011 8 vikramjit singhSlide 9: A single tape is applied to a stainless steel plate or a suitable backing membrane of choice and then tape is pulled from the substrate at a 180° angle, and the force required for tape removal is measured. 4/10/2011 9 vikramjit singhSlide 10: 4/10/2011 10 The force is expressed in term of ounces(or grams) per inch width of tape, the higher values indicate greater bond strength. No residue on the substrate indicates adhesive failure which is desirable for Transdermal devices. Remnant on the substrate indicates cohesive failure signifying a deficit of cohesive strength in the coating. vikramjit singhTACK PROPERTIES: TACK PROPERTIES Tack is the ability of a polymer to adhere to a substrate with little contact pressure. It is important in case of T.D.D. System which are applied with finger pressure. Tack is dependent upon the molecular weight and composition of polymer as well as the use of tackifying resin in the polymer. 4/10/2011 11 vikramjit singhSlide 12: Generally there are 4 test which are used for tack determination : Thumb tack test Rolling ball tack test Quick stick tack test Probe tack test 4/10/2011 12 vikramjit singhSlide 13: Thumb tack test: It is a quantitative test applied for the determination of tack property. In this test, thumb is simply pressed on the adhesive and the relative tack property is detected. By experience one can differentiate between relative degree of tack. 4/10/2011 13 vikramjit singhSlide 14: Rolling ball tack test: This test measures the softness of a polymer that relates to tack. In this test, a stainless steel ball of 7/16 inches in diameter is released on an inclined track so that it rolls down and comes in contact with horizontal, upward facing adhesive. The distance the ball travels along the adhesive provides the measurement of tack, which is usually expressed in inches. 4/10/2011 14 vikramjit singhSlide 15: ROLLING BALL TRACT Ball (diameter = 7/16 inches) Slope = 22.5° The less tacky the adhesive, the farther the ball will travel. 4/10/2011 15 vikramjit singhSlide 16: Quick stick tack (peel-tack) test: In this test , the tapped is pulled away from the substrate at 90° at the speed of 12 inches/min. The peel force required to break the bond between adhesive and substrate is measured and recorded as tack value, which is expressed in ounces (or grams) per inch width. The higher the value of force required indicates the higher degree of tack. 4/10/2011 16 vikramjit singhSlide 17: Probe tack test: In this test probe tack tester is used. The tip of the clean probe with a defined surface roughness is brought into contact with adhesive and a bond is formed between the probe and adhesive. The subsequent removal of the probe mechanically break it. The force required to pull the probe away from the adhesive at fixed rate is recorded as tack (expressed in grams). 4/10/2011 17 vikramjit singhSHEAR STRENGTH PROPERTIES: SHEAR STRENGTH PROPERTIES It is the measure of the cohesive strength of an adhesive polymer. If Transdermal device has adequate cohesive strength, it will not slip after application and will leave no residue upon removal. In this particular test, adhesive-coated tape is applied onto a stainless steel plate. A specified weight is hung from the tape to affect its pulling in a direction parallel to the plate. Shear strength is determined by measuring the time it takes to pull the tape off the plate. The longer time taken for removal, greater in a the shear strength. 4/10/2011 18 vikramjit singhSlide 19: Adhesive Tensile & Shear Tester 4/10/2011 19 Shear strength test vikramjit singhIN VITRO STUDIES: IN VITRO STUDIES The design and development of Transdermal drug delivery system is greatly aided by in vitro studies. In vitro studies can help in investigating the mechanism of skin permeation of the drug before it can be developed into a Transdermal therapeutic system. Information such as the time needed to attain steady state permeation and the permeation flux at steady state can be obtained from in vitro studies of the developed Transdermal drug delivery systems. It is used to optimize the formulation before more expensive in vivo studies are performed. 4/10/2011 20 vikramjit singhSlide 21: Advantages of in vitro studies: Ease of methodology Ease of analytical assay Reason : Since there are no complications arising from the disposition of the drug in the body and better control over experimental condition than is possible in vivo. 4/10/2011 21 vikramjit singhSlide 22: Transdermal therapeutic systems are evaluated for their drug release and permeation studies by using a two compartment diffusion cell assembly under identical condition. These include Valia-Chien cell, Ghannam-Chien membrane permeation cell, Jhawer-Lord rotating disc system, Franz diffusion cell and Keshary –Chien cell. 4/10/2011 22 vikramjit singhFRANZ DIFFUSION CELL: FRANZ DIFFUSION CELL 4/10/2011 23 vikramjit singhSlide 24: 4/10/2011 24 vikramjit singhVALIA-CHIEN CELL: VALIA-CHIEN CELL 4/10/2011 25 vikramjit singhPROCEDURE: PROCEDURE The release and skin permeation studies of the drug from Transdermal drug delivery system can be carried out by individually mounting a skin specimen excised from either a human cadaver or a live animal (guinea pig skin, hairless mouse skin) on a vertical diffusion cell, such as the Franz diffusion cell and its modification or a horizontal diffusion cell, such as Valia-Chein skin permeation cell. 4/10/2011 26 vikramjit singhSlide 27: Each unit of the Transdermal drug delivery system 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 pre-determined intervals until the steady flux is established and assaying drug concentrations in the sample by a sensitive analytical methods, such as high performance liquid chromatography. 4/10/2011 27 vikramjit singhIN VITRO DRUG RELEASE STUDIES: IN VITRO DRUG RELEASE STUDIES Using a Franz diffusion cell assembly, the rates of drug release from Transdermal drug delivery system can be evaluated and compared. For e.g.: in case of nitroglycerine T.D.D. System, the release of nitroglycerine from Transderm-Nitro (a polymer membrane permeation-controlled T.D.D. System) and Deponit (a drug reservoir gradient-controlled T.D.D. System) can be compared by plotting the data for cumulative amount of drug released from these system as a function of time (Q versus t) 4/10/2011 28 vikramjit singhRESULT: RESULT It is found that the release rate of nitroglycerine from Transderm-nitro system (0.843 ± 0.035mg/cm 2 /day) is almost three times greater than that from the Deponit system (0.324 ± 0.011 mg/cm 2 /day). This suggest that diffusion through the rate controlling adhesive polymer matrix in Deponit system plays a greater rate-limiting role over the release of nitroglycerine than does permeation through the rate-controlling polymer membrane in the Transderm-nitro system. 4/10/2011 29 vikramjit singhIN VITRO SKIN PERMEATION STUDIES: IN VITRO SKIN PERMEATION STUDIES In vitro permeation kinetic studies can be performed on hairless mouse skin or human cadaver skin by using Valia-Chien permeation cell. Animal skin model: The permeation of nitroglycerine across hairless mouse skin from different T.D.D. Systems was compared for their kinetics. The rate of skin permeation and the rate of release was compared. 4/10/2011 30 vikramjit singhRESULT: RESULT The skin permeation studies of these T.D.D. Systems suggested that all 4 systems give a constant rate of skin permeation. T.D.D. Systems Rate of skin permeation (mg/cm 2 /day) Nitro-Disc 0.426 ± 0.024 Nitro-Dur 0.408 ± 0.024 Transderm-Nitro 0.388 ± 0.017 Deponit 0.175 ± 0.16 4/10/2011 31 vikramjit singhSlide 32: A comparison made between the rate of skin permeation and the rate of release suggest that under sink condition all T.D.D. System deliver nitroglycerine at a rate greater than its rate of permeation across the skin. For e.g. T.D.D. System Rate of drug delivery (mg/cm 2 /day) Rate of skin permeation (mg/cm 2 /day) Transderm-Nitro 0.843 0.338 Deponit 0.324 0.175 4/10/2011 32 vikramjit singhSlide 33: This phenomenon is an indication that the stratum corneum plays a rate-limiting role in the Transdermal delivery of drugs, including the relative skin permeable nitroglycerine, as a result of its extremely low permeability coefficient. The difference in skin permeation rates among the various T.D.D. System could be attributed to the variation in the formulation design that affects the magnitude of the partition coefficient. 4/10/2011 33 vikramjit singhSlide 34: Human cadaver skin model: The permeation of nitroglycerine across the skin of human cadaver was also investigated for various nitroglycerine T.D.D. System using the Valia-Chien skin permeation cell assembly. RESULT It indicate that the skin permeation of nitroglycerine through human cadaver skin following the delivery from all the T.D.D. Systems evaluated also follows the same zero-order kinetic profile as observed with hairless mouse abdominal skin. 4/10/2011 34 vikramjit singhSlide 35: It has also been seen that difference in the type and thickness of a skin specimen and variation in the hydrodynamics of in vitro skin permeation cell could affect interspecies correlation in skin permeation rates. Drugs T.D.D System Permeation rate ( μ g/cm 2 /hr) Human cadaver Hairless mouse Nitroglycerine Transderm-Nitro 19.21 14.08 Nitro-Dur 20.29 17.01 Nitro disc ----- 17.75 Deponit ----- 7.29 Estradiol Estraderm 0.27 0.40 Clonidine Catapres-TTS 2.05 3.62 4/10/2011 35 vikramjit singhCONCLUSION: CONCLUSION For better correlation, a skin model with a controlled source, such as hairless mouse, and a skin permeation cell with well-calibrated hydrodynamics, like Valia-Chien skin permeation cells, should be used in skin permeation kinetics studies 4/10/2011 36 vikramjit singhCONCLUSION: CONCLUSION Conventional drug delivery is being replaced by various forms of modified-release dosage technology. Currently there is a significant emphasis on research and development of new drug delivery systems with controllable as well as predictable drug release characteristics for old drug as well. 4/10/2011 37 vikramjit singhSlide 38: This advancement, however, has significantly affected the quality assurance as well as quality control departments of the drug industry. A variety of variables, previously unknown, that influences the drug release characteristics have surfaced with even more force than usual. In-vitro dissolution testing, one of the most powerful quality control tools, has changed significantly and many new modifications are currently underway which hopefully, will assist in addressing the various problems. 4/10/2011 38 vikramjit singhREFERENCE: REFERENCE Vyas SP, Khar RK. Controlled drug delivery. 1 st ed. Delhi: Vallabh Prakashan; 2002. Jain NK, Controlled and Novel Drug Delivery, 1 st ed. Reprint2004. Delhi: CBS Publishers & Distributors; 2002. Robinson JR, Lee HL. Controlled drug delivery. 2 nd ed. New York: Marcel Dekker; 1987. Chien Y W. Novel Drug Delivery System.2 nd ed. New York: Marcel Dekker Inc. p.443-449 4/10/2011 39 vikramjit singhTHANK YOU: THANK YOU 4/10/2011 40 vikramjit singh You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.