Transdermal Drug Delivery System


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Transdermal Drug Delivery System

  1. 1. Transdermal drug delivery system
  2. 2. Introduction1,2 -The use of the transdermal route has been well established since the1800s.There is considerable interest in the skin as a site of drug application bothfor local and systemic effects.Transdermal drug delivery systems allow delivery of a drug into thesystemic circulation via permeation through skin layers at a controlled rate.The skin poses an extremely good barrier to drug penetration and it isusually necessary to employ enhancement strategies.Innovative research exploiting penetration-enhancing strategies, such asiontophoresis, electroporation, microneedles, and sonophoresis, holdspromise for the successful use of these drugs as consumer-friendly, transdermal dosage forms in clinical practice.
  3. 3. Objective - To explore skin as a site for drug administration. To identify physicochemical properties of drug required in development of TDDs. To study various methods for preparation of TDDs. To study various methods for evaluation of TDDs.
  4. 4. Advantages of TDDS2 - Avoids the risk and inconvenience of intravenous therapy. Usually provides less chance of an overdose or under dose. Permit both local and systemic effects . Reduces dosing frequency. Avoids hepatic first pass elimination and gastrointestinal irritation. Non-invasive drug delivery system. Improve physiological and pharmacological responses. Reduction of fluctuations in plasma levels of drugs. Allow easy termination. Utilization of drug candidates with short half-life and low therapeutic index. Reduction of dosing frequency and patient compliance.
  5. 5. Disadvantages of TDDS7 - TDDS cannot deliver ionic drugs. TDDS cannot achieve high drug levels in blood/plasma. 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.
  6. 6. PERCUTANEOUS ABSORPTION7 -Percutaneous absorption is defined as penetration of substances intovarious layers of skin and permeation across the skin into systemiccirculations.The percutaneous absorption is a step-wise process and can be divided intothree parts:Penetration : is the entry of a substance into a particular layer.Permeation : is the penetration from one layer into another, and is differentboth functionally and structurally from the first layer.Absorption : is the uptake of a substance into systemic circulation.
  8. 8. Anatomy of skin cont… Drug molecules in contact with skin surface can penetrated by three potential pathways, through *sweat ducts, *via the hair follicles and *sebaceous glands. *Stratum corneum.
  9. 9. Ideal properties of drug used for TDDS1Parameter Properties Dose  Should be low (>20 mg/day) Half life in „h‟  10 or less Molecular weight  <400 Partition coefficient  Log P (octanol-water) between 1-4 Skin permeability coefficient  >0.510 -3 cm/hr Skin reaction  Non irritating and non sensitizing Oral bioavailability  Low Therapeutic index  Low
  10. 10. Approaches of TDDS3,4,6,7.Various technologies have been developed to bypass or modulate the barrier function of the skin and to allow easier passage of drugs into the dermal microcirculation; these can be categorized into physical and chemical. Physical Approaches Chemical Approaches. Iontophoresis . Electroporation . prodrug approaches. Microporation. penetration Enhancer. Heat. Needless injection. Medicated tattos. Sonophoresis. Pressure valve Radio Frequency. Magnetophoresis
  11. 11. Physical Approaches.1. Iontophoresis- Iontophoresis is the process of enhancing the permeation of topically applied therapeutic agents. The drug is applied under an electrode of the same charge as the drug, and an indifferent counter electrode is positioned elsewhere on the body. The active electrode effectively repels the active substance and forces it into the skin and rough the skin by the application of electric current. Mechanisms. First mechanism proposes that the drug is forced across the skin by simple electronic repulsion of similar charges. Anionic drugs can cross the skin by using a negatively charged working electrode. Similarly, cationic drugs can cross the skin when a positively charged electrode is used. The second the electric current enhances the permeation by inhibiting the skins ability to perform its protective barrier function.
  12. 12. Mechanism of Iontophoresis
  13. 13. 2. Electroporation. Electroporation is another electrical enhancement method which involves the application of short (microsecond or millisecond), high voltage (50-1000 volts) pulses to the skin. Larger macromolecules have also been delivered by electroporation, including insulin, vaccines, oligonucleotides, and microparticles. A few model compounds such as calcein and LHRH drugs have also been studied for increased transdermal absorption by electroporation. Mechanism. The mechanism of penetration is the formation of transient pores due to electric pulses that subsequently allow the passage of macromolecules from the outside of the cell to the intracellular space via a combination of processes
  14. 14. 3.Microporation - Microporation involves the use of microneedles that are applied to the skin so that they pierce only the stratum corneum and increase skin permeability. Microneedles are needles that are 10 to 200 µm in height and 10 to 50 µm in width. Microneedles do not stimulate the nerves, so the patient does not experience pain or discomfort. They are usually drug coated projections of solid silicon or hollow, drug filled metal needles.
  15. 15. 4 .Heat - Heat enhances the skin permeation of drugs by increasing body fluid circulation, blood vessel wall permeability, rate-limiting membrane permeability, and drug solubility, thus facilitating drug transfer to the systemic circulation. Example: The effect of temperature on in vitro transdermal fentanyl flux was estimated at temperatures of 32 and 37 C. Drug flux approximately doubled over this 5 range. Heat may also cause changes in physiochemical properties of patches, sweating, and increased hydration of skin, thus increasing the permeation of drugs. Mechanism : When heat is applied, the kinetic energy of drug molecules, proteins, lipids, and carbohydrates is known to increase in the cell membrane. Also, drug solubility both in the patch and within the skin may increase with a rise in temperature.
  16. 16. 5.Needleless injection - Needleless injection involves a pain-free method of administration of drugs to the skin. This technique involves firing the liquid or solid particles at supersonic speeds through the stratum corneum. Problems with this technique include the high developmental cost for both the device and dosage form and the inability to program or control drug delivery to compensate for intersubject differences in skin permeability. Mechanism The mechanism involves forcing compressed gas such as helium or nitrogen through the nozzle with the resultant drug particles entrained within the jet flow, reportedly traveling at sufficient velocity for skin penetration.
  17. 17. 6.Medicated tattoos - Medicated tattoos are a modification of temporary tattoos which contain an active drug medicament for transdermal delivery. They are very attractive and fun to wear and are applied by wetting with water and pressing against the skin. The tattoo contains a drug layer, a colour design layer, and an adhesive layer that binds to the skin. There is no predetermined duration of therapy. The manufacturer provides a colours chart that can be compared to the colours of the patients tattoo to determine when the tattoo should be removed. It gives a visual indication as the drug is absorbed into the skin. Upon absorption, the tattoo gradually fades away and is painless to remove with a simple astringent wash containing isopropyl alcohol. The drugs used in medicated tattoos prototypes include acetaminophen, vitamin C etc.
  18. 18. 7.Pressure waves - Pressure waves generated by intense laser radiation, can permeabilize the stratum corneum as well as the cell membrane. PW is only applied for a very short time (100ns-1µs). It is thought that the pressure waves form a continuous or hydrophilic pathway across the skin due to expansion of lacunae domains in the stratum corneum.A single pressure wave is sufficient to permeabilize the stratum corneum and allow the transport of macromolecules into the epidermis and dermis. In addition, the drug delivered into the epidermis can enter the vasculature and produce a systemic effect. Example: Insulin delivered by pressure waves resulted in reducing the blood glucose level over many hours. The application of pressure waves does not cause any pain or discomfort and the barrier function of the stratum corneum always recovers.
  19. 19. 8.Sonophoresis - Sonophoresis is a technique which involves the use of ultrasonic energy to enhance skin penetration of active substances. Transdermal enhancement is particularly significant at low frequency regimes (20 KHz < f <100 KHz) than when induced by high frequency ultrasound. Ultrasound parameters such as treatment duration, intensity, pulse length, and frequency are all known to affect percutaneous absorption with frequency being the most important. Example: Sonophoresis of hypotensive agents and papain has been used in the treatment of eye diseases. Several antibiotics including tetracycline, biomycin, and penicillin have been sonophoretically administered for the therapy of skin diseases.
  20. 20. MechanismThe mechanism of transdermal skin permeation involves the disruptionof the stratum corneum lipids by the formation of gaseous cavities, thusallowing the drug to pass through the skin.
  21. 21. 9.Magnetophoresis - The term, "magnetophoresis" was used to indicate application of a magnetic field and acts as an external driving force to enhance drug delivery across the skin. It induces alteration in the skins structure that could contribute to an increase in permeability. Magnetoliposomes consist of magnetic nanoparticles wrapped by a phospholipid bilayer which can be successfully applied for drug delivery systems, magnetic resonance imaging markers for cancer diagnosis, and thermal cancer therapy.
  22. 22. 10.Radiofrequency - Radiofrequency involves exposure of the skin to a high frequency alternating current of 100 KHz that results in the formation of heat-induced microchannels in the cell membrane. The drug delivery rate is controlled by the number and depth of microchannels formed, which depends on the properties of the microelectrodes in contact with the skin during treatment. Skin delivery of testosterone and human growth hormone are in progress by use of this method.
  23. 23. Chemical approaches
  24. 24. 1. Penetration enhancer - Incorporation of penetration enhancers facilitates the absorption of drugs by altering the barrier property of the stratum corneum. A permeation enhancer should be pharmacologically inert, nontoxic, nonirritating, nonallergic, odorless, tasteless, colorless, com patible with most drug and excipients, inexpensive, and have good solvent properties. Different classes of penetration enhancers includes: Alcohols and polyols (ethanol, propylene glycol). Surfactants (Tween, Span, SLS). Fatty acids (Oleic acid). Amines and amides (Azone, N -methylpyrrolidone). Terpenes (limonene). Sulfoxides (dimethylsulfoxide) Esters(isopropylmyristate).
  25. 25. Mechanism: Permeation enhancers can enhance the skin permeability by a variety of mechanisms, including1. Interaction with intercellular lipids leading to disruption of their organization and increasing their fluidity.2. Extraction of lipids from the stratum corneum.3. Displacement of bound water,4. Loosening of horny cells,5. Delamination of stratum corneum.6. Enhancing solubility and7. Increasing partitioning into the stratum corneum,8. Interaction with intercellular protein, and keratin denaturation.
  26. 26. 2.Prodrug - Prodrugs are therapeutically inactive derivatives of therapeutically active drugs. A prodrug undergoes metabolism to produce the therapeutically active drug. A prodrug is more lipophilic than the parent drug and has different physicochemical properties. Different prodrugs were developed for estradiol and "Transdermal Bioactive Hormone Delivery" devices were developed based on the results. The release rate of estradiol from Transdermal Bioactive Hormone Delivery is dependent on the chain length of the ester group at the 17 th position. Alkyl ester prodrugs of ketorolac having optimum lipophilicity could improve the transdermal delivery of ketorolac. Also, the prodrug approach is a very feasible way to increase the skin permeation of protein/peptide drugs.
  27. 27. Fig. Schematic representation of pro-drug approach to increase drug penetration across skin7 .
  28. 28. Formulation aspects1:Basic Components Of TDDS: Polymer matrix / Drug reservoir Drug Permeation enhancers Pressure sensitive adhesive (PSA) Backing laminates Release liner Other excipients like plasticizers and solvents
  29. 29. Polymer matrix / Drug reservoir -Polymers are the backbone of TDDS, which control the release of the drugfrom the device.Polymer matrix can be prepared by dispersion of drug in liquid or solidstate synthetic polymer base.Polymers used in TDDS should have biocompatibility and chemicalcompatibility with the drug and other components of the system such aspenetration enhancers and PSAs.Additionally they should provide consistent and effective delivery of adrug throughout the product‟s intended shelf life and should be of safestatus.
  30. 30. Examples: Natural Polymers: e.g. cellulose derivatives, zein, gelatin, shellac, waxes, gums, natural rubber and chitosan etc.  Synthetic Elastomers: e.g. polybutadiene, hydrin rubber, polyisobutylene, silicon rubber, nitrile, acrylonitrile, neoprene, butylrubber etc. Synthetic Polymers: e.g. polyvinyl alcohol, polyvinylchloride, polyethylene, polypropylene, polyacrylate, polyamide, polyurea, polyvinylpyrrolidone, polymethylmethacrylate etc.
  31. 31. Drug:The transdermal route is an extremely attractive option for the drugs withappropriate pharmacology and physical chemistry.Transdermal patches offer much to drugs which undergo extensive firstpass metabolism, drugs with narrow therapeutic window, or drugs withshort half life which causes non- compliance due to frequent dosing.The foremost requirement of TDDS is that the drug possesses the right mixof physicochemical and biological properties for transdermal drug delivery.It is generally accepted that the best drug candidates for passive adhesivetransdermal patches must be; non ionic,of low molecular weight (less than 500 Daltons), have adequate solubility in oil and water (log P in the range of 1-3), a low melting point (less than 200 C) potent (dose in mg per day).
  32. 32. Permeation Enhancers:These are the chemical compounds that increase permeabilityof stratum corneum so as to attain higher therapeutic levels ofthe drug candidate.Penetration enhancers interact with structural components ofstratum corneum i.e., proteins or lipids.They alter the protein and lipid packaging of stratumcorneum, thus chemically modifying the barrier functionsleading to increased permeability .Over the last 20 years, a tremendous amount of work has beendirected towards the search for specificchemicals, combination of chemicals, which can act aspenetration enhancers.
  33. 33. Pressure sensitive adhesives:A PSA is a material that helps in maintaining an intimate contact betweentransdermal system and the skin surface.It should adhere with not more than applied finger pressure, be aggressivelyand permanently tachy, exert a strong holding force.Additionally, it should be removable from the smooth surface without leaving aresidue.Polyacrylates, polyisobutylene and silicon based adhesives are widely used inTDDSs.The selection of an adhesive is based on numerous factors, includingthe patch design and drug formulation. For matrix systems with a peripheraladhesive, an incidental contact between the adhesive and the drug andpenetration enhancer should not cause instability of the drug, penetrationenhancer or the adhesive.In case of reservoir systems that include a face adhesive, the diffusing drugmust not affect the adhesive. In case of drug-in-adhesive matrix systems, the selection will be based on therate at which the drug and the penetration enhancer will diffuse through theadhesive.Ideally, PSA should be physicochemically and biologically compatible andshould not alter drug release.
  34. 34. Backing Laminate:While designing a backing layer, the consideration of chemical resistance of thematerial is most important.Excipient compatibility should also be considered because the prolongedcontact between the backing layer and the excipients may cause the additives toleach out of the backing layer or may lead to diffusion of excipients, drug orpenetration enhancer through the layer.However, an overemphasis on the chemical resistance may lead to stiffness andhigh occlusivity to moisture vapor and air, causing patches to lift and possiblyirritate the skin during long wear.The most comfortable backing will be the one that exhibits lowest modulus orhigh flexibility, good oxygen transmission and a high moisture vaportransmission rate.Examples :vinyl,polyethyleneand polyester films.
  35. 35. Release Liner:During storage the patch is covered by a protective liner that is removed anddischarged immediately before the application of the patch to skin.It is therefore regarded as a part of the primary packaging material rather than apart of dosage form for delivering the drug.However, as the liner is in intimate contact with the delivery system, it shouldcomply with specific requirements regarding chemical inertness andpermeation to the drug, penetration enhancer and water.Typically, release liner is composed of a base layer which may be non-occlusive (e.g. paper fabric) or occlusive (e.g. polyethylene, polyvinylchloride)and a release coating layer made up of silicon or teflon.Other materials used for TDDS release liner include polyester foil andmetallized laminates.
  36. 36. Other excipients:Various solvents such as chloroform, methanol, acetone, isopropanol anddichloromethane are used to prepare drug reservoir .In addition plasticizers such as dibutylpthalate, triethylcitrate, polyethyleneglycol and propylene glycol are added to provide plasticity to thetransdermal patch.
  37. 37. VARIOUS METHODS FOR PREPARATION TDDS4:a. Asymmetric TPX membrane method.b. Circular teflon mould method.c. Mercury substrate method.d. By using “IPM membranes” method.e. By using “EVAC membranes” method.f. Aluminium backed adhesive film method.
  38. 38. Asymmetric TPX membrane method: A prototype patch can be fabricated for this a heat sealable polyester film (type 1009, 3m) with a concave of 1cm diameter will be used as the backing membrane. Drug sample dispensed into concave membrane Covered by TPX (poly-4-mthl-1- pentene) Sealed by adhesive
  39. 39. Circular teflon mould method:Polymer solution (in various ratio) + Organic Solvent Drug dissolve in half amount of same organic solvent calculated Enhancer (in different concentration)+ Different ratio of drug & solvent Addition of Di-N-butylphthalate Stir 12hrs & pour into Circular teflon mouldThe solvent is allowed to evaporate for 24 hrs. The dried films are to be stored foranother 24hrs at 25 0.5 C in a desiccators containing silica gel before evaluation toeliminate aging effects. The type films are to be evaluated within one week of theirpreparation.
  40. 40. Mercury substrate method:Drug is dissolve in polymer solution along with plasticizer Stir for 10-15 minutes to produce a homogenous dispersion pour in to a leveled mercury surface, covered with inverted funnel to control solvent evaporation
  41. 41. By using “IPM membranes” method: drug is dispersed in a mixture of water andpropylene glycol containing carbomer 940 polymer stir for 12 hrs in magnetic stirrer dispersion is to be neutralized and made viscous by the addition of triethanolamine Buffer pH 7.4 can be used in order to obtain solution gel The formed gel will be incorporated in the IPM membrane
  42. 42. By using “EVAC membranes” method:The proliposomes are prepared by carrier methodusing film deposition technique. From the earlier reference drug and lecithin in the ratio of 0.1:2.0 can be used as an optimized one. The proliposomes are prepared by taking5mg of mannitol powder in a 100 ml round bottom flask which is kept at 60-70 c temperature and the flask is rotated at 80-90 rpm and dried the mannitol at vacuum for30 minutes.
  43. 43. After drying, the temperature of the waterbathis adjusted to 20-30 C. Drug and lecithin are dissolved in asuitable organic solvent mixture, a 0.5ml aliquot of theorganic solution is introduced into the round bottomedflask at 37 C, after complete drying second aliquots(0.5ml) of the solution is to be added. After the last loading, the flask containing proliposomes are connected in a lyophilizer and subsequently drug loaded mannitol powders (proliposomes) are placed in a desiccator over night and then sieved through 100 mesh.
  44. 44. The collected powder is transferred into a glass bottle and stored at the freeze temperature until characterization.
  45. 45. Aluminium backed adhesive film method:Free film of cellulose acetate is prepared bycasting on mercury surface. A polymer solution 2% w/w is to be prepared by using chloroform. Plasticizers are to be incorporated at a concentration of 40% w/w of polymer weight. Five ml of polymer solution was poured in a glass ring which is placed over the mercury surface in a glass petri dish. The rate of evaporation of the solvent is controlled by placing an inverted funnel over the petri dish.
  46. 46. The film formation is noted by observing themercury surface after complete evaporation of thesolvent. The dry film will be separated out and stored between the sheets of wax paper in a desiccator until use. Free films of different thickness can be prepared by changing the volume of the polymer solution.
  47. 47. Evaluation1,4,7: 11. Peel Adhesion test:1. Interaction studies:2. Thickness of the patch: 12. Flatness test:3. Weight uniformity: 13. Percentage Elongation break test:4. Folding endurance: 14. Rolling ball tack test:5. Percentage Moisture content: 15. Quick Stick (peel-tack) test: 16. Skin Irritation study:6. Percentage Moisture uptake: 17. In vitro drug release studies:7. Drug content: 18. In vitro skin permeation studies:8. Water vapour permeability (WVP) 19. Stability studies:evaluation:9. Uniformity of dosage unit test:10. Shear Adhesion test:
  48. 48. 1. Interaction studies:Excipients are integral components of almost all pharmaceutical dosageforms. The stability of a formulation amongst other factors depends on thecompatibility of the drug with the excipients.The drug and the excipients must be compatible with one another toproduce a product that is stable, thus it is mandatory to detect any possiblephysical or chemical interaction as it can affect the bioavailability andstability of the drug.If the excipients are new and have not been used in formulations containingthe active substance, the compatibility studies play an important role informulation development.Interaction studies are commonly carried out in Thermal analysis, FT-IR, UV and chromatographic techniques by comparing theirphysicochemical characters such as assay, meltingendotherms, characteristic wave numbers, absorption maxima etc.,
  49. 49. 2. Thickness of the patch: The thickness of the drug loaded patch is measured in different points by using a digital micrometer and determines the average thickness and standard deviation for the same to ensure the thickness of the prepared patch.3. Weight uniformity: The prepared patches are to be dried at 60 c for 4hrs before testing. A specified area of patch is to be cut in different parts of the patch and weigh in digital balance. The average weight and standard deviation values are to be calculated from the individual weights.
  50. 50. 4. Folding endurance: A strip of specific are is to be cut evenly and repeatedly folded at the same place till it broke. The number of times the film could be folded at the same place without breaking gave the value of the folding endurance.5. Percentage Moisture content: The prepared films are to be weighed individually and to be kept in adesiccator containing fused calcium chloride at room temperature for 24hrs. After 24 hrs the films are to be reweighed and determine thepercentage moisture content from the below mentioned formula. Percentage moisture content = [Initial weight- Final weight/ Final weight] 100.
  51. 51. 6. Percentage Moisture uptake: The weighed films are to be kept in a desiccator at room temperature for 24 hrs containing saturated solution of potassium chloride in order to maintain 84% RH. After 24 hrs the films are to be reweighed and determine the percentage moisture uptake from the below mentioned formula. Percentage moisture uptake = [Final weight- Initial weight/ initial weight] 100.7. Drug content: A specified area of patch is to be dissolved in a suitable solvent in specific volume. Then the solution is to be filtered through a filter medium and analyse the drug contain with the suitable method (UV or HPLC technique). Each value represents average of three different samples.
  52. 52. 8. Water vapour permeability (WVP) evaluation: The WVP can be determined by the following formula Water vapour permeability can be determined with foam dressing method the air forced oven is replaced by a natural air circulation oven. WVP=W/AWhere, WVP is expressed in gm/m2 per 24hrs,W is the amount of vapour permeated through the patch expressed in gm/24hrs and A is the surface area of the exposure samples expressed in m2.
  53. 53. 9. Uniformity of dosage unit test: An accurately weighed portion of the patch is to be cut into small pieces and transferred to a specific volume volumetric flask, dissolved in a suitable solvent and sonicate for complete extraction of drug from the patch and made up to the mark with same. The resulting solution was allowed to settle for about an hour, and the supernatant was suitably diluted to give the desired concentration with suitable solvent. The solution was filtered using 0.2m membrane filter and analysed by suitable analytical technique (UV or HPLC) and the drug content per piece will be calculated.
  54. 54. 10. Shear Adhesion test: This test is to be performed for the measurement of the cohesive strength of an adhesive polymer. It can be influenced by the molecular weight, the degree of crosslinking and the composition of polymer, type and the amount of tackifier added. An adhesive coated tape is applied onto a stainless steel plate; a specified weight is hung from the tape, to affect it pulling in a direction parallel to the plate. Shear adhesion strength is determined by measuring the time it takes to pull the tape off the plate. The longer the time take for removal, greater is the shear strength.
  55. 55. 11. Peel Adhesion test: In this test, the force required to remove an adhesive coating form a test substrate is referred to as peel adhesion. Molecular weight of adhesive polymer, the type and amount of additives are the variables that determined the peel adhesion properties. A single tape is applied to a stainless steel plate or a backing membrane of choice and then tape is pulled from the substrate at a 180º angle, and the force required for tape removed is measured.12. Flatness test: Three longitudinal strips are to be cut from each film at different portion like one from the center, other one from the left side, and another one from the right side. The length of each strip was measured and the variation in length because of non-uniformity in flatness was measured by determining percent constriction, with 0% constriction equivalent to 100% flatness.
  56. 56. 13. Percentage Elongation break test: The percentage elongation break is to be determined by noting the length just before the break point, the percentage elongation can be determined from the below mentioned formula. Elongation percentage = L1-L2 100 L2 Where, L1is the final length of each strip and L2 is the initial length of each strip.14. Rolling ball tack test: This test measures the softness of a polymer that relates to talk. In this test, stainless steel ball of 7/16 inches in diameter is released on an inclined track so that it rolls down and comes into contact with horizontal, upward facing adhesive. The distance the ball travels along the adhesive provides the measurement of tack, which is expressed in inch.
  57. 57. 15. Quick Stick (peel-tack) test: In this test, the tape is pulled away from the substrate at 90ºC at a 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.16. Skin Irritation study: Skin irritation and sensitization testing can be performed on healthy rabbits (average weight 1.2 to 1.5 kg). The dorsal surface (50cm2) of the rabbit is to be cleaned and remove the hair from the clean dorsal surface by shaving and clean the surface by using rectified spirit and the representative formulations can be applied over the skin. The patch is to be removed after 24 hr and the skin is to be observed and classified into 5 grades on the basis of the severity of skin injury.
  58. 58. 17. In vitro drug release studies: The paddle over disc method (USP apparatus V) can be employed for assessment of the release of the drug from the prepared patches. Dry films of known thickness is to be cut into definite shape, weighed, and fixed over a glass plate with an adhesive. The glass plate was then placed in a 500-ml of the dissolution medium or phosphate buffer (pH 7.4), and the apparatus was equilibrated to 32 0.5 C. The paddle was then set at a distance of 2.5 cm from the glass plate and operated at a speed of 50 rpm. Samples (5- ml aliquots) can be withdrawn at appropriate time intervals up to 24 h and analyzed by UV spectrophotometer or HPLC. The experiment is to be performed in triplicate and the mean value can be calculated.
  59. 59. 18. In vitro skin permeation studies: An in vitro permeation study can be carried out by using diffusion cell. Full thickness abdominal skin of male Wistar rats weighing 200 to 250g. Hair from the abdominal region is to be removed carefully by using a electric clipper; the dermal side of the skin was thoroughly cleaned with distilled water to remove any adhering tissues or blood vessels, equilibrated for an hour in dissolution medium or phosphate buffer pH 7.4 before starting the experiment and was placed on a magnetic stirrer with a small magnetic needle for uniform distribution of the diffusant. The temperature of the cell was maintained at 32 0.5 C using a thermostatically controlled heater. The isolated rat skin piece is to be mounted between the compartments of the diffusion cell, with the epidermis facing upward into the donor compartment. Sample volume of definite volume is to be removed from the receptor compartment at regular intervals, and an equal volume of fresh medium is to be replaced. Samples are to be filtered through filtering medium and can be analyzed spectrophotometrically or HPLC. Flux can be determined directly as the slope of the curve between the steady-state values of the amount of drug permeated (mg cm2) vs. time in hours and permeability coefficients were deduced by dividing the flux by the initial drug load (mg cm2).
  60. 60. 19. Stability studies: Stability studies are to be conducted according to the ICH guidelines by storing the TDDS samples at 40 0.5 c and 75 5% RH for 6 months. The samples were withdrawn at 0, 30, 60, 90 and 180 days and analyze suitably for the drug content.
  61. 61. Conclusion - Transdermal drug delivery system has been recognized as a potential delivery system in spite of its limitation. Essentially this drug delivery system brings ratecontrolled delivery with fewer side effects , increased efficacy and constant delivery. The skin has an extremely good barrier function and to improve the penetration of active ingredients it is frequently necessary to employ enhancement strategies.
  62. 62. References - Geeta Agrawal,Dr.Sanjiv Dhawan,Development fabrication and evaluation of TDDS, Review,Vol.7 Issue 5-2010 A. E. Benson TDDS Penetration enhancement Technology 2005 bentham Science Publisher limited. Bharkatya M,Neema RK,Skin Penetration Enhancement Technique,J Young Pharmacist 2009;110-5. J Ashok Kumar ,Nikhila pullakandan, S. Lakshamana prabu,V.Gopal,Faculty Of Pharmacist,PRIST University, Thanjavur, Tamilnadu-614904.
  63. 63. Indian Journal Of Pharmaceutical Sciences, ReviewArticle,Year-2008,Volume-70,Issue-1,Page no-5-10.Swati Rawat, SudhaVengurlekar,B.Rakesh,S.Jain,G.Srikarti,SmritiCollege Of Pharmaceutical Education Indore-452010,India Mathur et al Enhancer in TDDS,Asian Journal OfPharmaceutical Sciences, nov-2010. Ramesh Panchagnula,Transdermal Delivery of drugIndian Journal of Pharmacology July-1997.
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