TRANSDERMAL DRUG TRANSDERMAL DRUG DELIVERYDELIVERY

POONAM PARASHARPOONAM PARASHAR

LECTURERLECTURER

M. PHARM (PHARMACEUTICS)M. PHARM (PHARMACEUTICS)

STRUCTURE OF SKINSTRUCTURE OF SKINPercutaneous AbsorptionPercutaneous Absorption

The absorption of substances from outside the skin to positions beneath the skin, direct penetration of the drug through the stratum corneum.

1. Transcellular penetration (across the cells)2. Intercellular penetration (between the cells)3. Transappendageal penetration (via hair follicles, sweat and sebum glands, and pilosebaceous apparatus)Penetration of the Skin by DrugsPenetration of the Skin by Drugs

The main route for the penetration of drug is generally through the epidermal layers, rather than through the hair follicles or the gland ducts, because the bigger surface area to the area of the skin.

Ideal Properties of a Transdermal Drug Delivery System

Properties Comments Shelf life Up to 2 years Patch size < 40 cm2

Dose frequency Once daily to once a week Aesthetic appeal Clear, tan or white color Packaging Easy removal of release liner and minimum

number of steps required to apply Skin reaction Non irritating and nonsensitizing Release Consistent pharmacokinetic and pharmacodynamic profiles over time

Advantages of Transdermal Delivery Advantages of Transdermal Delivery SystemsSystems

Reasonably constant dosage can be maintained (as opposed to peaks and Reasonably constant dosage can be maintained (as opposed to peaks and valleys associated with oral dosage)valleys associated with oral dosage)

First pass metabolism in the liver and GI tract is avoidedFirst pass metabolism in the liver and GI tract is avoided Easy to apply and to monitorEasy to apply and to monitor Sustains therapeutic drug levelsSustains therapeutic drug levels Permits self-administrationPermits self-administration Non-invasive (no needles or injections)Non-invasive (no needles or injections) Improves patient complianceImproves patient compliance Reduces side effectsReduces side effects Allows removal of drug source & Termination of further administration, if Allows removal of drug source & Termination of further administration, if

necessarynecessary

Administration of drugs with:Administration of drugs with:- A very short half-life- A very short half-life- Narrow therapeutic window- Narrow therapeutic window- Poor oral absorption - Poor oral absorption

Limitations of Transdermal Delivery Limitations of Transdermal Delivery SystemsSystems

Skin structure poses a barrier on the mw of the Skin structure poses a barrier on the mw of the drug (< 500 Da)drug (< 500 Da)

Can’t be used for drugs which get metabolized Can’t be used for drugs which get metabolized in skinin skin

Usually reserved for drugs which are Usually reserved for drugs which are extremely potent (thus requiring a dosage of extremely potent (thus requiring a dosage of only a few mg). only a few mg).

Poor penetration Poor penetration

Ideal Drug Candidate

PROPERTYPROPERTY RANGERANGE

Log PLog P 1.0 to 4

Molecular weightMolecular weight < 500 dalton< 500 dalton

Melting pointMelting point <200 °C

Half lifeHalf life <10 hrs<10 hrs

DoseDose <20mg<20mg

Transdermal Drug Delivery SystemsTransdermal Drug Delivery Systems

Polymer Membrane Permeation Controlled TDDS.Polymer Membrane Permeation Controlled TDDS.

Polymer Matrix Diffusion Controlled TDDS.Polymer Matrix Diffusion Controlled TDDS.

Drug Reservoir Gradient Controlled TDDS.Drug Reservoir Gradient Controlled TDDS.

Microreservoir Dissolution Controlled TDDSMicroreservoir Dissolution Controlled TDDS..

Nitrodisc (Nitroglycerin; Searle) In this type, drug Nitrodisc (Nitroglycerin; Searle) In this type, drug reservoir is fabricated by micro dispersion of an reservoir is fabricated by micro dispersion of an aqueous Suspension of drug in biocompatible aqueous Suspension of drug in biocompatible polymer to form homogeneous dispersion.polymer to form homogeneous dispersion.

Film Backing

Drug/Adhesive Layer

Protective Liner (removed prior to use)

skin

Schematic Drawing of the Matrix (Drug-in-Adhesive) type of patch.

Film Backing

Drug Layer

Protective Peel Strip (removed prior to use)

skin

Schematic Drawing of the Reservoir type of patch.

Rate-controlling Membrane

Contact Adhesive

Release linerRelease liner : Protects the drug during storage and is : Protects the drug during storage and is removed prior to use ; silicon PE polypropyleneremoved prior to use ; silicon PE polypropylene

DrugDrug : solution or coated vehicle ;mineral oil,polyisobutylene : solution or coated vehicle ;mineral oil,polyisobutylene

AdhesiveAdhesive : Serves to bind the components of the patch to the : Serves to bind the components of the patch to the skin; Polyisobutyleneskin; Polyisobutylene

Rate controlling membraneRate controlling membrane: Controls the release of the drug : Controls the release of the drug from the reservoir PVC, Polyacrylonitritefrom the reservoir PVC, Polyacrylonitrite

BackingBacking : Protects the patch from the outer environment ; : Protects the patch from the outer environment ; metallized PE, metallized PVCmetallized PE, metallized PVC

NOVEL CARRIERS FOR ENHANCED TDDSNOVEL CARRIERS FOR ENHANCED TDDS

LIPOSOMESLIPOSOMES NIOSOMESNIOSOMES ETHOSOMESETHOSOMES TRANSFEROSOMESTRANSFEROSOMES

EVALUATION PARAMETERSEVALUATION PARAMETERS

SpreadibiltySpreadibilty ExtruditibilityExtruditibility Uniformity drug contentUniformity drug content Texture(spreadibilty)Texture(spreadibilty) Thickness of patchThickness of patch In vitroIn vitro drug release drug release In vitro skin permeationIn vitro skin permeation StabilityStability

MARKETED PRODUCTSMARKETED PRODUCTS

BRAND NAMEBRAND NAME DRUGDRUG USEUSE

Catapres TTS Catapres TTS ®® CLONIDINE CLONIDINE

WEEKLYWEEKLY

HypertensionHypertension

Ortho-EvraOrtho-Evra®® Ethinylestradiol (EO) and Ethinylestradiol (EO) and norelgestromin (N) norelgestromin (N) WEEKLYWEEKLY

ContraceptionContraception

Nitro-DurNitro-Dur®®, Transderm-, Transderm-NitroNitro®®

Nitroglycerin DRUG IN Nitroglycerin DRUG IN ADHESIVE TYPE ADHESIVE TYPE (DAILY)(DAILY)

AnginaAngina

LidodermLidoderm®® LidocaineLidocaine

RESERVOIR (DAILY)RESERVOIR (DAILY)

Painful condition caused by Painful condition caused by the varicella zoster virusthe varicella zoster virus

HabitrolHabitrol®®, Nicoderm – , Nicoderm – CQCQ®®, Nicotrol, Nicotrol®®, Prostep, Prostep®®

NicotineNicotine

DAILYDAILY

Smoking cessationSmoking cessation

REFERENCESREFERENCES Scheindlin Stanley Transdermal drug delivery: PAST, Scheindlin Stanley Transdermal drug delivery: PAST,

PRESENT, FUTURE. Molecular interventions (2004), PRESENT, FUTURE. Molecular interventions (2004), 4(6), 308-12.4(6), 308-12.

Dixit Nitin; Bali Vikas; Baboota Sanjula; Ahuja Alka; Ali Dixit Nitin; Bali Vikas; Baboota Sanjula; Ahuja Alka; Ali Javed Iontophoresis - an approach for controlled drug Javed Iontophoresis - an approach for controlled drug delivery: a review. Current drug delivery (2007), 4(1), 1-delivery: a review. Current drug delivery (2007), 4(1), 1-1010Novel drug delivery system- Y.W.Chien. Novel drug delivery system- Y.W.Chien.

Pg no. 1-132Pg no. 1-132Fundamentals of controlled release drug delivery- Robinson. Fundamentals of controlled release drug delivery- Robinson. Pg no. 482 - 508Pg no. 482 - 508Web – www.google.comWeb – www.google.com