Dermal drug delivery system

Abstract

A device for brushing the skin prior to applying a topical preparation of a drug enhances the permeability of the stratum corneum to the drug.

1 . A mechanised brushing device, wherein the mechanism of the device is adapted to rotate a brush in contact with the skin of a patient, the device having abutment means for contact with the skin, the brush being movably located in relation to the abutment means to allow it to be introduced to the skin, travel of the brush being limited in relation to the abutment means such that pressure on the brush to contact the skin is limited to a predefined range.  
   
   
       2 . A device according to  claim 1 , further comprising pressure limiting means.  
   
   
       3 . A device according to  claim 1 , adapted to provide a contact pressure of the brush of between about 200 and about 1500 N m −2  on the skin.  
   
   
       4 . A device according to  claim 3 , wherein the pressure is between about 200 and about 1000 Nm −2 ,  
   
   
       5 . A device according to  claim 4 , wherein the pressure is about equal to, or greater than, 300 N m −2 .  
   
   
       6 . A device according to  claim 4 , wherein the pressure is between about 300 and about 600 N m −2 .  
   
   
       7 . A device according to  claim 1 , comprising a timing mechanism to limit the duration of the brushing.  
   
   
       8 . A device according to  claim 1 , adapted to provide brushing for between about 10 seconds and 5 minutes.  
   
   
       9 . A device according to  claim 8 , adapted to provide brushing for between about 10 seconds and about two minutes.  
   
   
       10 . A device according to  claim 8 , adapted to provide brushing for between about 20 seconds and one minute.  
   
   
       11 . A device according to  claim 8 , adapted to provide brushing for between about 30 seconds and about 50 seconds.  
   
   
       12 . A device according to  claim 1 , wherein the brush is substantially Robertson grade 8, and is adapted to provide brushing for between about 15 seconds to about 40 seconds.  
   
   
       13 . A device according to  claim 1 , adapted to provide an oscillatory brushing motion.  
   
   
       14 . A device according to  claim 13 , wherein the oscillatory motion is essentially circular.  
   
   
       15 . A device according to  claim 13 , wherein the rate of said motion is between 30 and 300 rpm.  
   
   
       16 . A device according to  claim 15 , wherein the rate of said motion is between 50 and 200 rpm.  
   
   
       17 . A device according to  claim 15 , wherein the rate of said motion is between 60 and 120 rpm.  
   
   
       18 . A device according to  claim 1 , wherein that part of the brush for contact with the skin consists essentially of bristles, and wherein said bristles have a Robertson number of from about 6 to about 11.  
   
   
       19 . A device according to  claim 18 , wherein the Robertson number is from about 7 to about 10.  
   
   
       20 . A device according to  claim 18 , wherein the Robertson number is from about 8 to about 9.  
   
   
       21 . A device according to  claim 18 , wherein the Robertson number is about 8.  
   
   
       22 . A device according to  claim 1 , wherein the cross-sectional area of that part of the brush for contact with the skin is between about 1 mm 2  and about 10 cm 2 .  
   
   
       23 . A device according to  claim 22 , wherein the cross-sectional area is about 4 mm 2  to about 5 cm 2 .  
   
   
       24 . A device according to  claim 22 , wherein the cross-sectional area is about 5 mm 2  to about 2 cm 2 .  
   
   
       25 . A method for the conditioning of skin to enhance transdermal delivery of drug, the method comprising continuous brushing for a period sufficient to reduce the barrier qualities of the stratum corneum.  
   
   
       26 . A method according to  claim 25 , comprising, substantially immediately after brushing the area of skin to be treated, applying said drug to the brushed area.  
   
   
       27 . A method for the conditioning of skin to enhance transdermal delivery of drug, the method comprising continuous brushing for a period sufficient to reduce the barrier qualities of the stratum corneum, wherein said brushing is provided by the mechanised brushing device of  claim 1 .  
   
   
       28 . A kit comprising the mechanised brushing device of  claim 1  and a drug wherein said drug is selected from the group consisting of: crotamiton, doxepin hydrochloride, mesulphen, polidocanol, amethocaine, amylocaine, benzocaine, bucricaine, butacaine sulphate, butyl aminobenzoate picrate, cincocaine, dimethisoquin hydrochloride, dyclocaine hydrochloride, ethyl chloride, lidocaine, lignocaine, myrtecaine, oxethazaine, prilocaine, propanocaine hydrochloride, tetracaine, antihistamines, antazoline, chlorcyclizine hydrochloride, dimethindene maleate, diphenhydramine, histapyrrodine, isothipendyl hydrochloride, mepyramine, mepyramine maleate, tolpropamine hydrochloride, tripelennamine hydrochloride, triprolidine hydrochloride, corticosteroids, alclometasone dipropionate, beclomethasone dipropionate, betamethasone valerate, clobetasol propionate, clobetasone butyrate, desoximetasone, diflucortolone valerate, fludroxycortide/flurandrenolone, fluocinolone acetonide, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, calcipotriol, coal tar, dithranol, 5-fluouracil, ciclosporin, fumeric acid, lonapalene, methotrexate, methoxsalen, salicylic acid, tacalcitol, tacrolimus, pimecrolimus, tazarotene, azelaic acid, benzoyl peroxide, amorolfine, benzoic acid, bifonazole, bromochlorosalicylanilide, buclosamide, butenafine hydrochloride, chlormidazole hydrochloride, chlorphenesin, ciclopirox olamine, clotrimazole, croconazole hydrochloride, eberconazole, econazole nitrate, fenticlor, fenticonazole nitrate, flutrimazole, haloprogin, ketoconazole, mepartricin, miconazole nitrate, naftifine hydrochloride, natamycin, neticonazole hydrochloride, nystatin, omoconazole nitrate, oxiconazole nitrate, pyrrolnitrin, sertaconazole nitrate, sodium propionate, sulbentine, sulconazole nitrate, sulconazole nitrate, terbinafine, tioconazole, tolciclate, tolnaftate, triacetin, undecenoates/undecanoic acid, 1-docosanol, aciclovir, brivudine, edoxudine, ibacitabine, idoxuridine, idoxuridine in dimethyl sulfoxide, imiquimod, penciclovir, vidarabine, benzyl benzoate, carbaryl, malathion, permethrin, phenothrin, cetrimide, collodion, magnesium sulphate, proflavine, heparinoid, antiperspirants, aluminium chloride, glycopyrronium bromide, and mixtures thereof.  
   
   
       29 . A kit comprising the mechanised brushing device of  claim 1  and a drug wherein said drug is selected from the group consisting of non-steroidal anti-inflammatories, actinic keratosis treatments, and capsaicin.  
   
   
       30 . A kit comprising the mechanised brushing device of  claim 1  and a drug wherein said drug is a hydrophilic drug.  
   
   
       31 . A kit according to  claim 30 , said drug having a Log P of ≦2.  
   
   
       32 . A kit according to  claim 30 , said drug having a Log P of ≦1.  
   
   
       33 . A kit according to  claim 30 , said drug having a Log P of 0 or below.  
   
   
       34 . A kit comprising the mechanised brushing device of  claim 1  and a drug wherein said drug is selected from the group consisting of: methotrexate, aciclovir, dactinomycin, oxytetracycline, 5-fluorouracil, ipatropium bomide, chlortetracycline, ceterizine, carboplatin, aminophylline, ofloxacin, pravastatin sodium, dichloromethotrexate, isoniaziad, theopylline, doxycyline, metronidazole, procaine, 4-aminosalicyclic acid, baclofen, triamcinolone, lidocaine/lignocaine, minoxidil, and combinations thereof.  
   
   
       35 . A kit comprising the mechanised brushing device of  claim 1  and a substance wherein said substance is a protein or peptide, nucleic acid, or a related compound.  
   
   
       36 . A kit according to  claim 35 , wherein said substance is capable of stimulating an immune response when applied to the skin by a device as defined in  claim 1.