Pharmaceutics III - Transdermal Drug Delivery PDF

1103-511 Pharmaceutics III TRANSDERMAL DRUG DELIVERY ↳ terminate further we can drug release...

1103-511 Pharmaceutics III TRANSDERMAL DRUG DELIVERY ↳ terminate further we can drug release the by removing Mutasem (Mark) Rawas-Qalaji patch B. Pharm (Hon.), Ph.D. t Advantage Associate Professor compared to other control release Department of Pharmaceutics & Pharmaceutical Technology formulations coral , implants) College of Pharmacy University of Sharjah  Definitions Text Transdermal formulations are designed to be applied to the skin for the purpose of delivering therapeutic quantities of the drug through the various skin layers into the general circulation for their systemic effect. Transdermal drug delivery systems (TDDSs), e.g. patches, are designed to support the passage of a drug through the skin. The target site of action is not the skin or skin surface. The potential for percutaneous absorption of drugs was first known in 1965. The first transdermal system, Transderm Scop by Ciba (Novartis), was approved by FDA in 1979 for the prevention of motion sickness. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 2 Approval year Drug/Product name Indication Marketing company 1979 Scopolamine/Transderm-Scop Motion sickness Novartis Consumer Health (Parsippany, NJ, USA) 1981 Nitroglycerin/Transderm-Nitro Angina pectoris Novartis (East Hannover, NJ, USA) 1984 Clonidine/Catapres-TTS Hypertension Boehringer Ingelheim (Ridgefield, CT, USA) 1986 Estradiol/Estraderm Menopausal symptoms Novartis 1990 Fentanyl/Duragesic Chronic pain Janssen Pharmaceutica (Titusville, NJ, USA) GlaxoSmithKline (Philadelphia), Novartis Consumer 1991 Nicotine/Nicoderm, Habitrol, ProStep Smoking cessation Health, Elan (Gainesville, GA, USA) 1993 Testosterone/Testoderm Testosterone deficiency Alza (Mountain View, CA, USA) Lidocaine with epinephrine 1995 Local dermal analgesia Iomed (Salt Lake City, UT, USA) (iontophoresis)/Iontocaine Estradiol with 1998 Menopausal symptoms Novartis norethidrone/Combipatch Post-herpetic neuralgia 1999 Lidocaine/Lidoderm Endo Pharmaceuticals (Chadds Ford, PA, USA) pain Ethinyl estradiol with 2001 Contraception Ortho-McNeil Pharmaceutical (Raritan, NJ, USA) norelgestromin/Ortho Evra Estradiol with levonorgestrel/Climara 2003 Menopausal symptoms Bayer Healthcare Pharmaceuticals (Wayne, NJ, USA) Pro 2003 Oxybutynin/Oxytrol Overactive bladder Watson Pharma (Corona, CA, USA) 2004 Lidocaine (ultrasound)/SonoPrep Local dermal anesthesia Echo Therapeutics (Franklin, MA, USA) 2005 Lidocaine with tetracaine/Synera Local dermal analgesia Endo Pharmaceuticals 2006 Fentanyl HCl (iontophoresis)/Ionsys Acute postoperative pain Alza Attention deficit 2006 Methylphenidate/Daytrana Shire (Wayne, PA, USA) hyperactivity disorder 2006 Selegiline/Emsam Major depressive disorder Bristol-Myers Squibb (Princeton, NJ, USA) 2007 Rotigotine/Neupro Parkinson's disease Schwarz Pharma (Mequon, WI, USA) 2007 Rivastigmine/Exelon Dementia Novartis  Transdermal sales Mutasem Rawas-Qalaji, 4 B.Pharm, Ph.D.  Transdermal sales Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 5  Advantages of Transdermal Drug Delivery Provides a steady drug concentration in the plasma. Avoids significant fluctuations between the peak and trough plasma drug concentrations, which may result in fewer side effects. Releases drug over an extended period of time (prolonged and predictable → pharmacological response) prolonged pretdictable Enhances disease managment Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 6  Very useful delivery option for drugs with short half- lives. Enhances patient compliance by reducing the dosing frequency. Bypass the GIT and the fist-pass hepatic effect. Reduce dosing errors and missed doses by patient. Drug therapy can be terminated by removing the transdermal patch. → best advantage It is convenient, user-friendly, non-invasive, and self- administered alternative route of administration. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 7  Selection Criteria (Limitations) for Transdermal Drug Delivery (TDD) Suitable for potent drugs because only small doses can be loaded into the patch. Suitable for drugs with small molecular weight (about 500 Da or rate limiting step less). Should have adequate solubility in both lipophilic and aqueous media to ensure permeability. need we to - make sure its Suitable for drugs that are extensively metabolized after oral not extensively metabolized administration or require frequent administration. in the skin too - chronic conditions Suitable for non-life-threatening conditions (slow onset of action) Drugs causing skin irritation or sensitization are not suitable for TDDS (contact dermatitis). Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 8 Skin Anatomy → extremely Skin covers an area of 1.73 m2 large surface and receives 1/3 of circulating area rd blood. increase size of patch to doesnt have d alot water → less permeable increase amount Stratum corneum (SC) is the of drug outermost desquamating\ absorbed. ‘horny’ layer of skin. The most challenging most difficult to penetrate cus of → the deeper the , more easily the prescence of can dead cells= less Comprises about 15-20 rows of the drug water to permeate. permibate flat, partially desiccated, keratinized epidermal cells. Thickness ranges from 10-20 μm. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 9  stratum corneum pis - solubility ofdrug or d permeability otmembrane SC is the rate-limiting barrier to percutaneous drug transport Considered the most difficult barrier for drug transport when compared to all epithelial barriers e.g. GI, nasal, buccal, vaginal, or rectal membranes. SC layer is composed of about 40% protein (mainly less " keratin), 40% water, and 20% lipids (triglycerides, free lipophilic) fatty acids, cholesterol, and phospholipids). Most of water ( the lipids surrounds the cells in the extracellular space. In general, once drug molecules cross SC barrier, passage into deeper dermal layers and systemic uptake occurs relatively quickly and easily. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 10  Drug Absorption Through Skin paraceuular Larger surface area Transport of lipophilic drug d d d ?gÉpetemed lipids route molecules is possible by their challenge - tonydrophilicbetwceenus drugs dissolution into intercellular d theories lnatusuauy lipids around the cells of SC. take that route ( polar) Transport of hydrophilic or charged molecules is difficult due to lipid-rich nature of SC and its low water content Transport through skin is by passive diffusion, which relies on drug characteristics Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 11  SO we 're limited to lipophilic d drugs. due to limited absorption very small surface area compared to skin surface C I %) f ] hydrophilic Hydrophilic molecules may water soluble ( take those routes to pass (sweat drugs through the skin glands + Hair follicle ) penetrate the skin through ‘pores’ or openings of hair 00 ⑧ follicles and sebaceous glands. But, the relative surface area of these openings is barely 1% of the total skin surface and their absorption capacity is very limited. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 12  Factors Affecting Percutaneous Absorption 1. Biological factors: * Regional skin sites (horny layer thickness). – The thinner the horny layer the easier the absorption – Skin behind ear is thinner and highly perfusable Skin condition 1- scrotum area of men – Inflammation and psoriasis increase skin absorption – Cuts, abrasions and dermatitis promote penetration Skin age – Premature infants may be born with no SC, i.e. drug absorption is high – No dramatic difference in skin absorption of young and the elderly Cain icarly] Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 13  Blood blow – Vasoconstricting agents such as topical steroids could reduce their own absorption or other drugs Skin metabolism to what extent the drug is metabolized in the skin – Prodrugs with good skin absorption can be designed. When they are metabolized in the skin enter the systemic circulation as active drugs, e.g. Prednisone Desquamation (shedding of skin layer) I removing dead skin) ↳ Cabrasion / expose the more premeable layer Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 14 2. Physico-chemical factors: Drug concentration: – Amount absorbed per surface area per time increases with the increase in drug concentration Surface area of application – The larger the surface area the more drug is absorbed Drug solubility – Drug solubility in both water and lipid is required Contact time with skin – The longer the time the greater the absorption. T residence time , more drug absorption Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 15  Partition coefficient (vehicle vs. skin) – Drug should be attracted (partitioned) to the skin more than the vehicle Y the lipophilic more → more partitioning pH and dissociation constant (pKa) into the skin – Unionized form of the drug penetrate better C the drug should want to stay in the Molecular weight, size and shape skin more than the vehicle ) – Ideal Mwt is 500 Dalton or less Skin hydration seals the area → any sweating will be retained / – Occlusive film (e.g. TDDS) increases hydration of skin due to sweating and increases skin absorption we need the skin to be hydrated to disslove the drug (but not creams or moisturisers cus its inc hydration like hella and we dont want this) Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 16  Kinetics of Transdermal Diffusion Follows Fick’s Law dQ/dt= DAK (Cvehicle– CP) / h Rate of drug transport across the skin is: – directly proportional to drug oil/water partition coefficient (K) – directly proportional to drug concentration in the formulation vehicle (Cvehicle) – directly proportional to the surface area of the skin to which it is exposed (A) – inversely proportional to the thickness of SC (h) Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 17 3. Formulation factors: TDDS design – Matrix vs. reservoir Drug formulation dissolve → still need to – Solid vs. liquid → faster absorption Penetration enhancers balanced with A. Chemical Enhancers (Passive) need to be side ellects - Ø They reversibly damage or alter the nature of the stratum corneum to reduce its diffusional resistance by: Ø Hydration of the skin Ø Change the structure of lipids and lipoproteins (denaturation). Ø E.g. acetone, ethanol, PEG, PG, azone, DMSO Ø Selection is based on efficacy, toxicity, compatibility Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 18  B. Physical enhancers (Active) difference – Iontopheresis → by applying → urea in charges Enhance the delivery of charged drug by battery AIM similar applying electrical field on the skin. : charges There is interest to be used to deliver proteins and peptides that are currently delivered by injection, e.g. large molecules, charged, poorly absorbed. ). E.g. ZECUITY® is indicated for the acute treatment ttttttt siynkcondition of migraine in adults. Designed for patient self-administration to the upper arm or thigh, should not be applied to other areas of the body and should not be cut. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 19  we use dissolving needles the one aint mentioned here should be polar and charged – Sonophoresis – Enhance the delivery of drugs by applying high-frequency ultrasound which creates pores and alters the integrity of stratum so corneum (disturb the lipids density in the intercellular spaces of SC). regular injections ( used for very potent drugs) smaller dose than → controlled – Microneedles ✗ 101000 → not immediate released release reservoir g. – Solid silicon needles (coated with drug) or hollow metal needles (filled with drug solution) penetrate SC layer to deliver drugs (smallforms piercing molecules, proteins, DNA or vaccines) into the body. and active – Skin permeability increases by 10,000-fold – Microneedle patch for flu vaccination → not all ✓ transdermal Theresa of controlled → type not patches are miaoneedees where the painful release Mutasem Rawas-Qalaji, B.Pharm, Ph.D. ( rapid / Slow release) 20 needles dissolve ↳ immediate eeeect ↳ depends on the polymer used  Design of TDDS The basic components of any TDDS include: 1. An outer backing film which should be: – occlusive (water resistant, drug impermeable, and low retains moisture moisture vapor transmission rate) to protect the system - and drug, and retain skin moisture to hydrate the site of application. fan be same color skinas – can be 2-3 mm thickness, transparent or pigmented film. usually beige – E.g. polypropylene, polyethylene, polyolefin. µ Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 21  - first-order because ghost of groomer 2. A drug(s) is dispersed (matrix system) or dissolved (reservoir usually hsliquid ↳ solid system) in an inert polymeric matrix, which provides a for matrix system not reservoir → support and control the rate of drug release for absorption. 3. A rate-controlling membranes (in reservoir design only), e.g. microporous polyethlene 4. An adhesive layer that sticks the patch to the skin, e.g. polybutyl acrylate. Two designs: 1) Peripheral adhesive: only around circumference of patch to form an adhesive rim around the portion where the drug will be released from. 2) Face adhesive: covers the entire face of the patch (very common). ↳ need make to sure cs > cars > Cy rate it does not affect controlling membrane the permeation of C1 the / creservoir drug C2 → adhesive material C. may contain rate omg ) a only in reservoir Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 22 matrix but there's no polymer  – Must be pressure-sensitive that sticks easily for the entire intended application time. (10 sec) Should not allect release d drug rate the – Non-irritating, easy peel-off, permits normal drug flux, face → compatible and safe. to decrease time adhesive - lag the – May contain drug to provide immediate drug release after application (reservoir systems). 5. A release liner, which needs to be peeled off before applying the patch to the skin. I Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 23  Rate of Drug Transport Either controlledcontrolling by: membrane) → patch crate 1. Device: When the rate of drug release to the stratum high cornium is less than the absorption capacity of the skin absorption → for that specific drug, then, drug transport is controlled capacity d by the device. L we need to [ reduced) slow it for rate controlling membrane OR - no nee ⇐ C. Reservoir down. 2. Skin: when the skin get saturated at the rate the drug is released from the device and no further drug release takes place until depletion of released drug, then, drug transport will be controlled by the skin. ↳ mostly matrix design ( drug release is not The rate of drug transport is proportional to the slowed surface area of the patch. down ) Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 24  release wqwataqnpsjfysfer-meski a nitseefcontrok.tn nsusuallynopursedeflect because still needs time it to Matrix (Monolithic) TDDS for the drugto * polymer used is permeate skin usually layers Cwewill. saturate biodegradable the skin but it needs time non f ↳ easier manufacture - topassinroucsnthe ↳ cheaper to stratumcorneamandget mostly - usually melted absorbed tothebkod) omdynappens A drug is dispersed (dissolved or blended) in a hydrophilic or in implants lipophilic polymer matrix ↳ depends on → most polymer times as water-insoluble usually we use The polymer controls the rate of drug release the properties Fabrication of the matrix TDDS: (ofthedneg whatever slows – The matrix is casted (molded) as a sheet or disc and dried.down drug – Then cut into individual units that has specific dimensions ) release containing certain dose (surface area and thickness) – Then mounted between the backing film and the frontal layer (adhesive layer). → dnegahd polymerin is dissolved / suspended vehicle that there is ghost here but it is neglictable an organic Laleroncsowhdherdntt → release evaporates vehicle evaporates Liner is suspended / dissolved. behind anyway ] Mutasem Rawas-Qalaji, B.Pharm, Ph.D. leaving drug 25  The amount of drug in the matrix, with regards to its equilibrium solubility and steady-state concentration gradient at stratum corneum, can be: ifpatchisfortsodallsiwe. rate release the don't want toaedineauickey - 1) without excess:nastoalwaysexceed release rate declines when drug → solubility saturation concentration in the TDDS is below the skin solubility Disadvantages limit (saturation), follows first order kinetics : → as there is a patch will ghost left ÷÷÷ / Most times → biodegradable → insoluble + non 2) with excess: release rate is maintained for a longer period - with still polymer drug init - Ctzrdof drug] canegiswasledduring application before it declines (more common) we need expensive force sale ↳ driving tomaresure change No rate-controlling membrane is present won't disposal Also, the adhesive material can be blended with the matrix, no separate adhesive layer (simple design) → adhesive is + polymer mixed with the d drug Simple Design Matrix System → wenaveto thinner →save space maresuretne adhesive doesn't Csimplestdesign) interact with the Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 26 skin for matrix  sealed - Reservoir (Membrane-Controlled) TDDS ↳ more expensive as you have to build a construct then introduce aformalationtsealit A drug reservoir in a form of liquid or gel is formulated. The drug release is controlled by a polymeric controlling membrane between the drug reservoir and the adhesive layer. The release rate is maintained constant by maintaining the drug solution in the reservoir saturated (follows zero-order). A small amount of the drug is added to the adhesive layer to provide immediate drug release after application. Ca > C2 >↳ - a → have to be adhesives C2 saturated with outside primed drug to go with Cz d drug Mutasem Rawas-Qalaji, B.Pharm, Ph.D. usually primed to 27 reduce lag time  expensive y Fabrication of reservoir TDDS: – The delivery unit is pre-constructed, then reservoir is filled with drug and sealed. easier for matrix - – Or by continuous process “lamination” of construction, filling, and sealing ↳ more difficult 2 1 3 Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 28 → used for chronic memorize the stalls → condition idea not names Transdermal Scopolamine First FDA approved patch to treat motion sickness (reservoir in oil TDDS). 0.5mg excess→ Contains 1.5 mg scopolamine and deliver 1 mg over 3 days. 200 µg is the priming dose in the adhesive layer. breservoirtype Continuous release is controlled by the microporous membrane and not the skin. rate ↳ controlling Applied behind the ear 4 hours membrane before the effect is required. & Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 29  Transdermal Nitroglycerin → noneedtomomorize Nitro-Dur®, Key (gel reservoir) gzeroorder Transderm-Nitro®, Novartis (reservoir) Nitrodisc®, Searrle Pharm (reservoir) - sirsotrder Deponit®, Schwarz Pharma (solid matrix) Minitran®, 3M Pharm (matrix) ↳ diffcdnegreleaserclle. Cfirstandzero notinlerchancfable orders Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 30  daily Used for the prophylactic treatment of angina. An excess amount of drug is added to ensure continuous drug release for the intended period of use Nitroglycerin has short half-life, very potent, rapidly metabolized in the liver. Applied once daily with an approximately 12 h ‘rest period’ to avoid tolerance. The delivery rate depends on the design of the system Patches can NOT be used interchangeably by patient. drug permeate might change amount of that pnyaration They should be applied to clean, dry, hairless area of already [ so we keep dry ) occlusive → film the chest, back, upper arms, or shoulders. creates moisture ↳ unless specified for exact location on the skin. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 31  zero order → Nitro-Dur® is a saturated suspension reservoir system that contains 5 mg nitroglycerin/cm2 of the patch and qcnanga e delivers 0.02 mg/hr/cm2. d system controlling another the release in addition to the rcuecontooving – Nitroglycerin is adsorbed on lactose that is suspended in membrane in the patch glycerol. → soeednegtnatpermealethroughsrin.cwnendnlgieaues.to contains Cd skin , , so but we– Non-adsorbed nitroglycerin the solution diffuse to skin.moreamg will be can't be sure liberated so – System get re-saturated and equilibrated by releasing ) from lactose allowed more nitroglycerin from lactose to solution. not I ↳ can't know whether its reservoir or matrix creates an equilibrium between the dnegonthesurfaceof Lactose Transderm-Nitro® delivers nitroglycerin 0.02mg/hr/cm2 drug and in glycerol of the patch. Nitroglycerin is adsorbed on lactose as reservoir system. Depoint® delivers nitroglycerin 0.013 mg/hr/cm2 of the patch. Matrix system is used. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 32  Minitran MINITRAN System Rated Total Nitro-glycerin System Size Release In Vivo* Content 0.1 mg/hr 3.3 cm2 9 mg 0.2 mg/hr 0.4 mg/hr 0.6 mg/hr I 6.7 cm2 13.3 cm2 20.0 cm2 1 18 mg 36 mg 54 mg → size is proportional to the release rate Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 33  for hypertension Transdermal Clonidine 7- days Catapres TTS® (Boehringer Ingelheim) was marketed in 1985 for hypertension. Good permeability Clonidine is lipid soluble and potent drug - Patch releases drug for 7 days, and replaced on a weekly basis. Applied to clean, dry, hairless area of the chest or upper arms. Achieves steady state after 2-3 days of initial application. Plasma levels is maintained for a 8 hrs after removal of the patch. n¥?÷n¥ short half life ( so the reason , ,, is some drug is sublayer Mutasem Rawas-Qalaji, B.Pharm, Ph.D. still in the of the skin ( especially that the drug is Lipid ) soluble 34  Transdermal Clonidine A reservoir system composed of 4 layers The amount of drug released is directly proportional to the area (available in different sizes) An excess amount of drug is added to ensure continuous drug release for 7 days. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 35  16-24 hours Transdermal Nicotine t same idea as Habitrol® (Novartis) NTG Nicoderm CQ® (SmithKline Beecham) Nicotrol® (McNeil) Prostep® (Lederle) Used as adjunct therapy in smoking cessation programs Not approved for use by anyone younger than 18 years old Several patches available in the market Alternative to nicotine chewing gum, lozenges, sublingual tablets etc. Available at different strengths, 7, 15, and 21 mg. To be worn for 16 to 24 h/day during the course of treatment of 6- 12 weeks. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 36  Transdermal Nicotine ↳ should not use the gum I smoke Course of treatment 6-12 weeks Applied to upper arm or upper front torso No smoking when wearing the patch Replaced daily Alternate sites Discarded properly (poisonous for children) ↳ patch still has remaining drug Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 37  Transdermal Estradiol Estraderm® (Novartis, gel reservoir system) Vivelle® (Novartis, matrix system) Climara® (Berlex, matrix system) Estraderm delivers 0.05 or 0.1 mg proportional → to the estradiol/day for 10 cm2 or 20 cm2 patch. area -noneedfornew formulation → when treated wedoublethedose , we increase same concentration. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 38 ofdnlg  twice or once / week Used for the treatment of menopause symptoms, female hypogonadism, estrogen deficiency. Orally administered estradiol is rapidly - snort ) metabolized in C potent drug the liver (t½ = 1 hr) into estrone and its conjugates, achieve therapeutic which require higher doses of estradiol. concentration → to Transdermal estradiol is absorbed with minimal skin metabolism and avoids side effects associated with higher dose of oral estrdiol and its metabolites. Patch applied twice/week (once/ week for Climara) for 3 weeks and off for 1 week. Patch is applied on the trunk, abdomen, or buttocks Patch should not be applied to the waistline to avoid damage by tight clothing. avoid areas of friction → Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 39  once / week Transdermal Contraceptives Ortho Evra® (Ortho-McNeil- Janssen Pharm., matrix system) reasons : into skin if its matrix then partition of drug [ Me ① properties ) + dose be different cane to might ② " "" """ " "" " " " " "£ "^" " " "* ⑨ " ② " "of driving force Contains 6 mg norelgestromin and 0.75 mg ethyl drug) estradiol/ 20 cm2 patch Releases 150 µg norelgestromin and 20 µg ethyl estradiol/24 hrs. Patch applied once a week on the shoulder, upper arm, lower abdomen, outer buttocks. 3 weeks on and 1 week off Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 40  daily in the morning Transdermal Testosterone Testoderm ( Alza, matrix system) Androderm (SmithKline Beecham, gel reservoir system) Hormonal replacement - therapy Testoderm is applied daily in the morning (to mimic testosterone release) Applied to the scrotal skin (5x more permeable) for 6-8 weeks. Plasma peak is reached 2-4 hrs after application. Androderm is applied to the back, abdomen, upper arm, or thighs. I can't be applied elsewhere Mutasem Rawas-Qalaji, B.Pharm, Ph.D. C decided by the manufacturer41  Patient Counseling Absorption may vary based on the site of application. The preferred site of application is stated in the package insert. - because theskinwillbeilerynydraled Location should be rotated within the site of application. towards the end , neauiresaweer-c-one.at → Wait 7 days before using a previously used site. Mone drug is Patch should be applied to clean, dry, hairless skin that is absorbed than cast Skin should be not oily, irritated, inflamed, or broken. paten. Site of application should avoid friction. has occlusive Can be worn during swimming and bathing. → film If patch is de-attached, it should be reapplied or replaced with a new one. Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 42  Lotion should be avoided because it alter skin hydration solid → therefore Like a tablet d partition coefficient. aasie-iointsg.EE#-s%EFIs okay for matrix design but we never Patches should not be cut (lose system integrity). know whether for reservoir ↳ , damaged itsang-msfealandatnefiau.EE matrix reservoir it will be as or Patch should be removed from package carefully to avoid its damage.. The protective liner should be removed to expose the adhesive layer without touching the exposed adhesive part of the patch and pressed against the skin for 10 sec. Should be worn for the full period instructed then removed and replaced with fresh one. Used patch should folded in half with the adhesive layer together and placed in the replacement patch’s pouch and discarded. → hard to be reached “4-18-2012: FDA evaluated a series of 26 cases of pediatric accidental exposures to ← fentanyl patches reported over the past 15 years. Of these 26 cases, 10 resulted in narcotics death and 12 in hospitalization. Sixteen of the 26 cases occurred in children two years old or younger.” Mutasem Rawas-Qalaji, B.Pharm, Ph.D. 43