transdermal drug delivery device

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  • , United States Patent [191

    Gockel et al. ...................... .. 428/43

    [11] Patent Number: 4,877,618 Reed, Jr. [45] Date of Patent: Oct. 31, 1989

    [54] IRANSDERMAL DRUG DELIVERY DEVICE ISqweeny ............................. .. , , W3. ser ....... .. '[76] Invento? g8! D-ff R2212 lg-601359- 4, BOX 855, 4,710,191 12/1987 Kwiatzk et a1. .................. .. 424/449

    . a stat , .

    [21] A l N 170g427 FOREIGN PATENT DOCUMENTS pp . 0.: ,

    0084817 5/1914 Ja an . [22] Filed: Mar. 18, 1988 0024811 5/1984 Jagan . [51] Int (:14 - . . . . . . .. A61K 9/68 8600806 2/1986 PCTMIAPP" '

    [52] U.S. Cl. .................................. .. 424/448; 424/449; OTHER PUBLICATIONS

    1581 Field Of Search ...................... 32432222251, Transdermal Delivery f Drug", 1- 1' Ag F- Kyde' 424/468-470 473 448 449 486- 604/8921 mus lib-D 6' 31' CRC Press Inc- (1987)

    Materials and Technology, vol. I, T. J. W. van [56] References Cited Thoor, Debussy, Ellerman, Harms NV, Amersterdam

    U.S. PATENT DOCUMENTS (1968)- . .

    2561071 7/1951 Prisk 128/260 (Llstcommued on next page) 3,249,109 5/1966 Maeth et a1. . . . . . . . .. 128/268 - - _ ' -

    3,598,122 4/1969 Zaffaroni 128/268 jglsgzz'ztigz?ggrigl? iflgbmson 3,742,951 7/1973 Zaffaroni . 128/268 A A F. ' ' cahin S & Th 3,797,494 10/1973 Zaffaroni . 128/268 tome? 8'3", 0' W1 4 no mas

    3,867,520 2/1974 Mori ....... .. 424/36 [57] ABSTRACT 3,936,573 2/1976 Brockett .. 428/402 - _ _ _ . _

    4,008,719 2/1976 Theeuwes 128/260 A transdermal drug dellvery devlce Includes a Plurahty 4,014,334 2/1976 Theeuwes 128/260 I of adhesive laminae containing the drug to be transder 4,058,122 12/1976 Theeuwes ...... .. 128/260 mally administered which laminae are separated by 4,060,034 1/1977 Chandrasekaran -- 128/260 alternating interlaminar layers within the device and 4,077,407 3/1973 meeu?es ------ -- 128/260 extending in stacked con?guration from a contact adhe i'gg'ig 313M111 6 a1" "" " sive for adhering the device to the epidermis of a user. 4286592 9/1981 128/260 Modulated migration of molecules of the drug serially 4:289:749 9/1981 Keith .............. .. " .... .. 424/28 ' fmm and thmugh the ,interlaminar layers 1, and 4,291,015 9/1981 Keith et al. .............. .. 424/28 thmklgh the _9I1ta_t adheslve results fmm the comm? 4,314,557 2/1982 Chandrasekamn ,, [28/260 physical equ1l1brat1on of the drug between the multiple 4,321,117 3/1982 Kaetsu et a1. 204/159 alternating interlaminar layers and adhesive lamine 4,329,333 5/1982 Barr . . . . . . . . . . . . . . . . . . . . . . .. 424/19 which, when Staeked, provide a relatively constant rate

    4,344,929 8/1982 Bnsen et al 124/15 of dermal diffusion to the skin surface (dermis) for an {Thalia-:1}; """ " extended period. Discharge of the drug other than

    4452775 6/1984 e 424/19 through the contact adhesive is precluded by an imper 4:46O:562 7/1984 Keith ' ' ' ' ' ' ' ' . _ _ " 424/28 meable backing layer. Side sealing may be necessary in

    4,464,434 8/1984 Davis .......... .. 428/402.22 89m: mstanies- ,Th? drug mm? 1 thls type f_de' 4,475,916 10/1984 Kimmelstein 604/890 vice may exist in e1ther an equilibrated or constrained 4,483,846 11/1984 Koide et a1. , . . . . . . . .. 424/19 physical-chemical state.

    4,485,087 3/ 1982 Otsuka et a1. 424/28 4,486,193 12/ 1984 Shaw et a1. .. 604/897 4,490,322 12/1984 Zierenberg 264/205 4,493,869 I/ 1985 Sweeny et al. 428/905 4,525,340 4/1983 Lange et al. . . . . . . . . .. 424/16

    4,524,095 10/1988 44 Claims, _5 Drawing Sheets

  • Page 2

    OTHER PUBLICATIONS

    Studies of Nichotines Effect on Brain Yield Ways to Kick Smoking Habit, David Stipp, The Wall Street Journal, p. 31, (Apr. 23, 1987). Transdermal Nicotine Reduces Cigarette Craving and Nicotine Preference, Jed E. Rose, Ph.D., et al., Clini

    cal Pharmacologv and Therapeutics 38(4), p. 450 (85), Transdermal Administration of Nicotine, Drug and

    Alcohol Dependence, I3, pp. 209-213 (1984). Dynamics Surface-Properties Due to Amine Migra tion and Chemical-Reaction in Primary Amilne Epox ide Systems; R. T. Foister, Journal of Colloid and Inter face Science, Vol. 99, No. 2, pp. 568-585, (1984). The In?uence of Diffusion and Chemical-Reaction on

    , Absorbtion Kinetics in Binary Surfactant Systems, R. T. Foister, Journal of Colloid and Interface Science, vol. 86, No. 2, pp. 386-410, (1983).

  • US. Patent 0ct.31,1989 Sheet 2 of 5 4,877,618 5

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  • US. Patent Oct. 31, 1989 Sheet3 0f5 4,877,618 54 Z00 20.

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  • US. Patent Oct.31, 1989 Sheet 4 of5 4,877,618

  • US. Patent Oct.31, 1989 Sheet 5 of5 4,877,618

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  • 1

    TRANSDERMAL DRUG DELIVERY DEVICE

    CROSS-REFERENCE TO RELATED DISCLOSURE

    Information relating to the invention described herein is contained in Disclosure Document No. 159164 ?led on July 14, 1986 by the present inventor, which information is incorporated herein by reference.

    BACKGROUND OF THE INVENTION

    1. Field of the Invention The present invention relates to drug delivery de

    vices and, more particularly, to transdermal drug deliv ery devices (TDDDs).

    2. Description of the Prior Art Delivery of drugs transdermally has been in practice

    for some time and various devices have been developed for such purpose. Such known devices may be catego rized as a reservoir device with a rate controlling mem brane, a reservoir device without a rate controlling membrane, a monolithic system .and a laminated struc ture. These devices are described in detail in Trans dermal Delivery of Drugs, Volume I, pages 7-11, ed ited by Agis F. Kydonieus and Bret Berner, published by CRC Press, Inc., Boca Raton, Fla. Various patents have also been directed to transdermal drug delivery devices. In example, US. Pat. No. 4,286,592 is directed to a device having a reservoir for the drug to be admin istered. A contact adhesive layer in ?uid communica tion with the reservoir serves in the manner of a conduit for transmission of the drug to an adhered skin surface. The adhesive layer equilibrates with the drug contain ing reservoir and determines the release rate for admin istration of the drug. Devices of this type generally provide a rapid initial administration followed by an asymptotically declining administration rate. For many drugs, such a varying rate of administration is unaccept able. In a monolithic type device the drug is disbursed throughout a carrier, layer or membrane in contact with the skin. In an adhesive dispersion type of device, the drug to be administered is disbursed throughout a layer of adhesive applied directly to the skin. The delivery rate of the latter two types of devices

    identi?ed above correspond closely with that of the reservoir type. That is, an initial rapid delivery rate exits which tapers, essentially asymptoically, over a period of time; the skin usually serves as the limiting factor of the absorption rate. Transdermal drug delivery devices have been used

    for the delivery of scopolamine to counteract the nausea attenant sea sickness or motion sickness in land based vehicles. Generally, administration of this drug for a relatively short period of time and at an imprecise or unpredictable rate still seems to provide acceptable and bene?cial results. For long term delivery of a speci?c drug, substantial control and regulation of the delivery rate may be of paramount importance.

    Substantial literature exists to describe the difficulty with and low success rate of breaking the smoking habit. Some studies have concluded that the drug nico tine may be as or more addictive than most other habit forming drugs, such as heroin, cocaine, etc. Aside from the physical addiction that smokers may have, social and emotional dependencies attendant the manipulation of the smoking related implements and visualization of the smoke itself can constitute additional dif?culties in breaking the smoking habit. Numerous experiments

    4,877,613

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    2 have been performed to explore the bene?cial effects of transdermal delivery of nicotine as an adjunct to or in combination with a smoking cessation program. Al though not conclusive, studies have indicated that transdermal administration of nicotine may be of assist ance to a smoke participating in a smoking cessation program by segregating different aspects of the habit and thereby permitting therapeutic work on each such aspect.

    Studies to date suggest that delivery of nicotine must extend commensurate with the normal smoking hours of a smoker. Furthermore, the delivery rate must be relatively commensurate with the depth of the smokers habit. Without such near duplication of the level of nicotine to which the smoker has been accustomed, the craving for nicotine may be too overpowering to permit effective work on breaking the related aspects of the smoking habit. Irritant, mutagenic and carcinogenic hydrocarbon molecules, the secondary detriments at tendant inhalation of smoke, which in fact may

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