Transdermal drug delivery system (TDDS) it's formulation and evaluation
- 1. TRANSDERMAL DRUG DELIVERY SYSTEM (TDDS) FORMULATION & EVALUATION SUBJECT : PHARMACEUTICS AND NANOTECHNOLOGY BY- S. DASH
- 3. INTRODUCTION Trans means across & dermal means skin. Therefore, transdermal means across the skin. (TDDS) are defined as self contained, discrete dosage forms which are also known as “patches”. These patches are applied to the intact skin, deliver the drug through the skin at a controlled rate to the systemic circulation. The first adhesive transdermal delivery system (TDDS) patch was approved by the Food and Drug Administration in 1979 (scopolamine patch for motion sickness). Nitroglycerine patches were approved in 1981.
- 4. GENERAL STRUCTURE AND BASIC COMPONENTS OF TDDS
- 5. GENERAL STRUCTURE OF TDDS All such transdermal dosage forms have a basic structure comprising of many layers, each having specific function. 1. Farthest from the skin, when the system is in place, is a backing layer, preventing wetting of the system during use. 2. The second layer is a reservoir that supplies a continuous quantum of drug for the predetermined functional life-time of the system. 3. Next to the reservoir is the rate control polymeric membrane which regulates the rate of drug during predetermined time interval. The drug so delivered diffuses through the skin and enters the systemic circulation. 4. Next is the adhesive layer it keeps the TDDS in contact with the skin and final layer is the liner which protect the drug during the storage.
- 6. PROPERTIES OF THE DRUG USED IN TDDS PHYSIOCHEMICAL PROPERTIES : 1. The drug should have a molecular weight of less than approximately 1000 daltons. 2. The drug should have affinity for both lipophilic and hydrophilic phases. 3. The drug should have low melting point. BIOLOGICAL PROPERTIES : 1. The drug should be potent with the daily dose of the order of a few mg/day. 2. The half life of the drug should be short. 3. Drug which degrade in the GI tract or rare inactivated by hepatic first-pass effect suitable candidates for transdermal delivery.
- 8. POLYMER MEMBRANE PERMEATION CONTROLLED TDDS In this system, the drug reservoir is embedded between an impervious backing layer and a rate controlling membrane. The drug releases only through the rate controlling membrane, which can be micro porous or non-porous. In the drug reservoir compartment, the drug can be in the form of a solution, suspension, or gel or dispersed in solid polymer matrix. Example : Scopolamine
- 9. ADHESIVE DIFFUSION CONTROLLED TDDS The drug reservoir is formed by dispersing the drug in an adhesive polymer and then spreading the medicated polymer adhesive by melting the adhesive (in case of hot-melt adhesives) onto an impervious backing layer. The drug reservoir layer is then covered by a non-medicated rate controlling adhesive polymer of constant thickness to produce an adhesive diffusion controlling drug delivery system. Example : Isosorbide dinitrate for Angina Pectoris
- 10. MATRIX DIFFUSION CONTROLLED TDDS The drug is dispersed homogenously in a hydrophilic or lipophilic polymer matrix. The drug containing polymer disk then is fixed onto an occlusive base plate in a compartment fabricated from a drug-impermeable backing layer. Instead of applying the adhesive on the face of the drug reservoir, it is spread along the circumference to form a strip of adhesive rim. Example : Nitro Dur (Nitroglycerin)
- 11. MICRORESERVOIR CONTROLLED TDDS This drug delivery system is a combination of reservoir and matrix- dispersion systems. The drug reservoir is formed by first suspending the drug in an aqueous solution of water-soluble polymer and then dispersing the solution homogenously in a lipophilic polymer to form thousands of unreachable, microscopic spheres of drug reservoirs. Example : Nitro Disc
- 12. FORMULATION
- 13. EVALUATION
- 14. PHYSIOCHEMICAL EVALUATION INTERACTION STUDIES These are done by thermal studies, FTIR, UV and chromatographic techniques by comparing their physicochemical properties like assay, melting point, wave numbers, absorption maxima. THICKNESS OF THE PATCH The thickness of the drug prepared patch is measured by using a digital micrometre at different point of patch and determines the average thickness and standard deviation for the same to ensure the thickness of the prepared patch. WEIGHT UNIFORMITY The prepared patches are to be dried at 60ºC for 4 hours 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.
- 15. WATER VAPOUR PERMEABILITY (WVP) EVALUATION WVP=W/A Where W is the amount of vapor permeated through the patch expressed in gm/24 hours and A is the surface area of the exposure samples expressed in metres. DRUG CONTENT A specified area of path 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 with suitable methods like UV or HPLC technique. PROBE TACK TEST In this test, the tip of a clean probe with a defined surface roughness is brought into contact with adhesive, and when a bond is formed between probe and adhesive. The subsequent removal of the probe mechanically breaks it. The force required to pull the probe away from the adhesive at fixed rate is recorded as tack and it is expressed in grams. Few other physiochemical evaluation include- folding endurance studies, percentage moisture content, content uniformity test, percentage elongation test, stability studies and many more.
- 16. IN VITRO EVALUATION a. In vitro drug release studies :- • The paddle over disc method 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 500ml of dissolution medium or phosphate buffer (pH- 7.4), and the apparatus was equilibrated to 32ºC. • The paddle was then set at a distance of 2.5cm 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 hours and analysed by UV spectrophotometer or HPLC.
- 17. a. In vitro skin permeation studies • Full thickness abdominal skin of male Wistar rats weighing 200-250 grams. Hair from the abdominal region is carefully removed by using an electric clipper. • The dermal side of the skin was thoroughly cleaned with distilled water to remove any adhering tissues or blood vessels. • Equilibrate 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 diffusion of diffusant. • The temperature of the cell was maintained at 32ºC 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 analysed 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 vs time in hours.
- 19. Animal Model Most common animal species used for evaluating TDDS are mouse, hairless rat, hairless dog, hairless rhesus etc. Rhesus monkey is one of the most reliable models for in vivo evaluation of TDDS in animals. Human volunteers The final stage of the development of a transdermal device involves collection of pharmacokinetic and pharmacodynamic data following application of the patch to human volunteers. It is divided into 4 phases :- PHASE-1 Conducted to determine safety in volunteers. PHASE-2 Conducted to determine the effectiveness in patients. PHASE-3 Conducted to check the safety and efficiency of the drug in large number of patient population. PHASE-4 Conducted to detect the adverse drug reactions on the patients’ body.
- 20. MARKET SHARE
- 21. EXAMPLES
- 22. MERITS : • Avoidance of first-pass effect. • Long duration of action. • Ease of termination of drug action, if necessary. • No interference with gastric and intestinal fluids. • Suitable for administration of drugs having- Very short half-life, e.g. nitroglycerine. Narrow therapeutic window. Poor oral availability.
- 23. DEMERITS : • Poor diffusion of large molecules. • Skin irritation. • Requires drug load. • Unsuitable if drug dose is large. • Absorption varies with different sites of skin.
- 24. REFERENCES : • Chandrasekaran, S. K., & Shaw, J. E. (1977). Design of transdermal therapeutic systems. In Contemporary topics in polymer science (pp. 291-308). Springer, Boston, MA. • Shaw, J. E. (1980). Drug delivery systems. In Annual Reports in Medicinal Chemistry (Vol. 15, pp. 302-315). Academic Press. • Keleb, E., Sharma, R. K., Mosa, E. B., & Aljahwi, A. A. Z. (2010). Transdermal drug delivery system-design and evaluation. International Journal of Advances in Pharmaceutical Sciences, 1(3). • Patel, D., Chaudhary, S. A., Parmar, B., & Bhura, N. (2012). Transdermal drug delivery system: a review. The pharma innovation, 1(4).
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