| In vivo skin penetration studies may be undertaken for one or more of the following purposes: | 1 To verify and quantify the cutaneous BIOAVAILABILITY of a topically applied drug.
2 To verify and quantify the systemic BIOAVAILABILITY of a transdermal drug.
3) To establish BIOEQUIVALENCE of different topical formulations of the same drug substance.
4) To determine the incidence and degree of systemic TOXICOLOGIC RISK following topical application of a specific drug or drug product.
5) To relate resultant blood levels of drug in human to systemic therapeutic effects. |
| IN VIVO STUDIES
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.
Animal models include: __
2 Biologic samples used in drug penetration and drug absorption studies include | 1 weanling pig, rhesus monkey, and hairless mouse or rat
2 skin sections,
venous blood from the application site,
blood from the systemic circulation, and
excreta (urine, feces, and expired air). |
| IN VITRO STUDIES
1 Skin permeation may be tested in vitro using various __ in a diffusion cell.
2 In vitro penetration studies using human skin are limited because of difficulties of __
3 Animal skins are much more permeable than human skin. One alternative that has been shown to be effective is __ | 1 skin tissues (human or animal whole skin, dermis or epidermis)
2 procurement, storage, expense, and variation in permeation.
3 shed snake skin (Elaphe obsoleta, black rat snake) |
| IN VITRO STUDIES
1 Test for cell culture studies or in standard diffusion cells | 1 Living Skin Equivalent Test skin |
| 1 are employed in vitro to quantify the release rates of drugs from topical preparations
2 In these systems, __ may be employed as barriers to the flow of drug and vehicle to simulate the biologic system | 1 Diffusion cell systems
2 skin membranes or synthetic membranes |
| Advantages of TDDSs | 1 AVOID GASTROINTESTINAL DRUG ABSORPTION DIFFICULTIES caused by gastrointestinal pH, enzymatic activity and drug interactions with food, drink, or other orally administered drugs.
2 SUBSTITUTE FOR ORAL ADMINISTRATION of medication when that route is unsuitable, as in instances of vomiting and/or diarrhea.
3. AVOID FIRST-PASS EFFECT
4. NONINVASIVE, AVOIDING THE INCONVENIENCE OF PARENTERAL THERAPY
5. EXTENDED THERAPY WITH SINGLE APPLICATION, thereby improving patient compliance over other dosage forms requiring more frequent dose administration.
6. The activity of drugs having short half-lives is extended through the reservoir of drug present in the therapeutic delivery system and its controlled release characteristics.
7 Drug therapy may be terminated rapidly by removal of the application from the surface of the skin.
8 Ease of rapid identification of the medication in emergencies (e.g., nonresponsive, unconscious, or comatose patient) due to the physical presence of TDDS |
| Disadvantages of TDDSs | 1. Only relatively POTENT DRUGS are suitable candidates for transdermal delivery due to the natural limits of drug entry imposed by the skin’s impermeability.
2. Some patients may develop CONTACT DERMATITIS at the site of application due to one or more of the system components, necessitating discontinuation. |
| Examples of transdermal drug delivery systems | 1 Transdermal scopolamine
2 Transdermal Nitroglycerin
3 Transdermal clonidine
4 Transdermal Nicotine
5 Transdermal Estradiol
SNCNE (SENSYA NA) |
| the first TDDS to receive FDA approval.
is a circular flat patch 0.2 mm thick and 2.5 cm2 in area. | Transdermal scopolamine (Transderm-Scop) |
| The TDDS (Transderm-Scop) contains __ and is designed to deliver approximately __ at an approximately constant rate to the systemic circulation over the __ life-time of the system. | 1) 1.5 mg of scopolamine
2) 1 mg of scopolamine
3) 3 day |
| Transdermal scopolamine (Transderm-Scop) is worn in __ | hairless area behind the ear.
Because of the small size of the patch, the system is unobtrusive, convenient, and well accepted by the patient. |
| used widely in the prophylactic treatment of angina.
It has a relatively low dose, short plasma half-life, high peak plasma levels, and inherent side effects when taken sublingually, a popular route.
It is rapidly metabolized by the liver when taken orally, this first-pass effect is bypassed by the transdermal route. | Nitroglycerin |
| A number of nitroglycerin-containing TDDSs have been developed: __ | 1 Deponit (Schwarz)
2 Minitran (3M Pharmaceuticals)
3 Nitro-Dur (Key)
4 Transderm-Nitro (Novartis)
Each of these products maintains nitroglycerin drug delivery for 24 HOURS after application. |
| 1 nitroglycerin 0.02 mg is delivered per hour for every square centimeter of patch
2 each square centimeter delivers approximately 0.013 mg of nitroglycerin per hour. | 1 Transderm-Nitro system
2 Deponit system |
| CONSTRUCTION OF NITROGLYCERIN SYSTEM
1 four-layer drug pouch system
2 thin two-layer matrix system resembling
3 Nitroglycerin TDDS should be placed in the __
4 may increase the absorption of nitroglycerin. | .
1 Transderm-Nitro TDDS
2 Deponit TDDS
3 chest, back, upper arms, or shoulders.
4 physical exercise and elevated ambient temperatures (such as in a sauna) |
