phardose - transdermal drug delivery system

Transdermal Drug Delivery System


• TermsTransdermal Drug Delivery SystemPercutaneous absorptionStratum corneum

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• MeaningFacilitate the passage of therapeutic

quantities of drug substances through the skin and into the general circulation for their systemic effects.

A transdermal patch or skin patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream.



• FactsIn 1965, Stoughton first conceived of the

percutaneous absorption of drug substances.

Transderm-Scop (Baxter) : The first transdermal system that was approved by the Food and Drug Administration in 1979 for prevention of nausea and vomiting associated with travel, particularly at sea.



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• Pathways of Drug Administration



• Mechanisms of Drug Permeation


Factors of affecting

percutaneous absorption

Factors affecting percutaneous absorption

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Drug Concentration

Area of Concentration

A drug that has a greater physicochemical attraction to the skin .

Drugs with molecular weighs of 100 to 800 and adequate lipid and aqueous solubility can permeate skin.

Hydration of the skin

Percutaneous absorption appears to be greater when the TDDS is applied to a site with a thin horny layer than with a thick one.

The longer the medicated application is permitted to remain in contact with the skin, the greater is the total drug absorption.

Percutaneous Absorption Enhancers

Main objective: To increase percutaneous absorption of

therapeutic agents.

Types of Permeation Enhancers


Physical Enhancers

•Iontophoresis•Sonophoresis•Electroporation

Chemical Enhancers

•Solvents•Surfactants


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Physical Enhancers

•Iontophoresis•Sonophoresis•Electroporation

• Sonophoresis : High-frequency ultrasound, is also being studied as a means to enhance transdermal drug delivery.

Among the agents examined are lidocaine, hydrocortisone, and salicyclic acid as gels, creams, and lotions.

• Iontophoresis : Is the delivery of a charged chemical compound across the skin membrane using an electric field.

Drugs that had been examined are lidocaine, dexamethasone, amino acids, peptides and insulin, verapamil, and propranolol.

• Electroporation : Apply short micro to millisecond electrical pulse approx. 100- 1000 v/cm to create temporary aqueous pore in lipid layer.


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• Solvents : Increase penetration by swelling the polar path or by fluidizing lipids. Ex. Dimethyl sulfoxide, oleic acid, propylene glycol, and etc.

• Surfactants : Lipid fluidization or penetration of it into intracellular matrix and result in disruption of order of comeocytes.

Ex. Anionic surfactants – dicotylsulphosuccinate, sodium lauryl

sulphate, and etc Non-ionic surfactants – Pluronic F 127 and Pluronic F68 Natural surfactants(bile salts) – Sodium taurocholate and

Sodium Tauroglycholate and etc.

Percutaneous Absorption Models

IN VIVO EVALUATION


Animal Model 1. The most common animal species used for evaluating transdermal drug delivery system are mouse, hairless rats, dogs, and rhesus monkey, rabbits, guinea pig, and etc. 2. Rhesus monkey – most reliable models for Vivo evaluation of transdermal drug delivery in man. 3. Alternative animals models include weanling pig and human skin grafted nude mouse.

Human Model 1. The most relevant studies are performed in humans however animal models may be used insofar as they may be effective as predictors of human response.

IN VITRO EVALUATION


Typical Franz diffusion cell - A method transdermal system is placed in between receptor and donor compartment of the diffusion cell.

IN VITRO EVALUATION


Typical side-by-side diffusion cell setup used for permeability/diffusion studies.

Design Features of Transdermal Drug Delivery SystemsOften called “Transdermal patches” that are designed to support the passage of drug substances from the surface of the skin through its various layers and into

systemic circulation.

Two types of Transdermal patches

Monolithic•Incorporate a drug matrix layer between the backing and the frontal layers.•Composed of a polymeric material in which the drug is dispered.•Two types of matrix: with or without an excess of drug with regard to its equilibrium solubility and steady-state concentration gradient at the stratum corneum.•As the concentration of the drug in the device diminishes below the skin’s saturation limit, the transport of drug from device to skin declines.•Ensures continuous drug availability and absorption as used TDDSs are replaced on schedule with fresh ones.

Membrane-controlled systems

•Designed to contain a drug reservoir or pouch, usually in liquid or gel form, rate- controlling membrane, and backing, adhesive, and protecting layers. •Ex. Transderm-Nitro (Summit) and Transderm-Scop (Baxter)•Has an advantage over Monolithic systems in that as long as the drug solution in the reservoir remains saturated, the release rate of drug through the controlling membrane remains constant.

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Transdermal patches

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• Other Facts:If the drug is delivered to the stratum corneum at a rate less than the absorption capacity, the device is the controlling factor.BUT if the drug is delivered to the skin area to saturation, the skin is the controlling factor.

TDDSs may be constructed of a number of layers: Occlusive backing membrane – To protect the system from

environmental-entry and from loss of drug from the system or moisture from the skin.

Drug reservoir/Matrix system – To store and release the drug at the skin site.

Release liner – which is removed before application and enables drug release.

Adhesive layer – To maintain contact with the skin after application.

Two types of adhesive 1. Peripheral adhesive 2. Face adhesive – most common.

Transdermal patches

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Design objectives are the following:

1. Deliver the drug to the skin for percutaneous absorption at therapeutic levels at an optimal rate.

2. Contain medicinal agents having the necessary physicochemical characteristics to release from the system and partition into the stratum corneum.

3. Occlude the skin to ensure one-way flux of the drug into the stratum corneum.

4. Have a therapeutic advantage over other dosage forms and drug delivery systems

5. Not irritate or sensitize the skin.6. Adhere well to the patient’s skin and have size,

appearance, and site placement that encourage acceptance.

Transdermal patches

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Advantages•Avoid gastrointestinal drug absorption difficulties…•Can substitute for oral administration of medication when that route is unsuitable as vomiting and diarrhea.

•Avoid first-pass effect•Are non invasive, avoiding the inconvenience of parenteral therapy.

•Provide extended therapy with a single application, improving compliance over other dosage forms requiring more frequent dose adminstration.

•The activity of drugs having a short half- life is extended through the reservoir of drug in the therapeutic delivery system and its controlled release.

•Drug therapy may be terminated rapidly by removal of the application from the surface of the skin.

•Are easily and rapidly identified in emergencies.

Disadvantages•Only relatively potent drugs are suitable candidates for transdermal delivery because of the natural limits of drug entry imposed by the skin’s impermeability.•Some patients develop contact dermatitis at the site of application from one or more of the system components, necessitating discontinuation.•The barrier function of skin changes from one site to another on the same person, from person to person and with age.•Limited only to potent molecules, those requiring a daily dose of 10 mg or less.•It is rather slow and sustained.•Does not adhere well to all types of skin.•Uncomfortable to wear•May not be economical

Examples of TDDSs

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Transdermal Scopolamine

Transdermal Nitroglycerin

Transdermal Clonidine

Transdermal Nicotine

Transdermal Estradiol

Transdermal Contraceptive

System

Transdermal Testosterone

Transdermal Methylphenidat

e

Other transdermal therapeutic system

General Clinical Considerations in the use of TDDSs

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1. Percutaneous absorption may vary with the site of application.

2. TDDSs should be applied to clean, dry skin that is relatively free of hair and not oily, irritated, inflamed, broken, or callused.

3. Use of skin lotion should be avoided at the application site because lotions affect skin hydration and can alter the partition coefficient between the drug and the skin.

4. TDDSs should not be physically altered by cutting since this destroys the integrity of the system.

5. A TDDS should be removed from its protective package, with care not to tear or cut into the unit.

6. A TDDS should be placed at a site that will not subject it to being rubbed off by clothing or movements.

General Clinical Considerations in the use of TDDSs

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7. A TDDS should be worn for the full period stated in the product’s instructions.8. The patient or caregiver should be instructed to cleanse their hands thoroughly before and after applying TDDS.9. If the patient exhibits sensitivity or intolerance to a

TDDS or if undue skin irritation results, the patient should seek re-evaluation.

10. Upon removal, a used TDDS should be folded in half with the adhesive layer together so that it cannot be reused. The used patch, which contains residual patch, should be placed in the replacement patch’s pouch and discarded in a manner safe to children and pets.

phardose - transdermal drug delivery system

Documents

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transdermal system

skin patch

percutaneous absorptionfactors

skin membrane

lipid layer

sodium tauroglycholate

rhesus monkey