An apparatus for transdermally delivering a nicotine-based agent to a tobacco or nicotine user comprising a microprojection member having a plurality of microprojections that are adapted to pierce the stratum corneum of the tobacco user, the microprojection member having a biocompatible coating disposed thereon that includes a nicotine-based agent.

Description of the Invention

SUMMARY OF THE INVENTION

In accordance with the above objects and those that will be mentioned and will become apparent below, the apparatus for transdermally delivering nicotine-based agents to a tobacco or nicotine user in accordance with this invention comprises a microprojection member having a plurality of microprojections that are adapted to pierce through the stratum corneum into the underlying epidermis and dermis layers of the nicotine user, the microprojection member having a biocompatible coating having at least one nicotine-based agent disposed thereon. Preferably, the nicotine-based agent is selected from the group consisting of nicotine base, nicotine salts and simple derivatives of nicotine.

As discussed in detail herein, upon piercing through the stratum corneum, the agent-containing coating is dissolved by body fluid (intracellular fluids and extracellular fluids, such as interstitial fluid) and released into the epidermis layer for systemic therapy (i.e., bolus delivery). The advantages of the invention thus include (i) effective transdermal bolus delivery of nicotine-based agents, (ii) rapid administration or on-set of nicotine, and (iii) effective treatment for break-through craving during tobacco quit attempts by administering small amounts of nicotine when needed. The invention further provides a convenient and easy to use method for supplementing nicotine replacement therapy.

Preferably, each of the microprojections has a length of less than 1000 microns, more preferably, less than 500 microns. In one embodiment of the invention, each microprojection has a length less than 250 microns.

The coating formulations that are employed to form the biocompatible coatings preferably include at least one wetting agent and, optionally, a hydrophilic polymer.

Preferably, the coating formulations include at least one surfactant, including, but not limited to, sodium lauroamphoacetate, sodium dodecyl sulfate (SDS), cetylpyridinium chloride (CPC), dodecyltrimethyl ammonium chloride (TMAC), benzalkonium, chloride, polysorbates such as Tween 20 and Tween 80, other sorbitan derivatives such as sorbitan laurate, and alkoxylated alcohols such as laureth-4. Most preferred surfactants include Tween 20, Tween 80, and SDS.

The coating formulations further preferably include at least one polymeric material that has amphiphilic properties, including, but not limited to, cellulose derivatives, such as hydroxyethylcellulose (HEC), hydroxypropylmethylcellulose (HPMC), hydroxypropycellulose (HPC), methylcellulose (MC), hydroxyethylmethylcellulose (HEMC), and ethylhydroxyethylcellulose (EHEC), as well as pluronics.

The coating formulations can further include a hydrophilic polymer. Preferably the hydrophilic polymer is selected from the following group: poly(vinyl alcohol), poly(ethylene oxide), poly(2-hydroxyethylmethacrylate), poly(n-vinyl pyrolidone), polyethylene glycol and mixtures thereof, and like polymers.

In a further embodiment of the invention, the coating formulations and, hence, biocompatible coatings include a vasoconstrictor. Preferably, the vasoconstrictor is selected from the group consisting of amidephrine, cafaminol, cyclopentamine, deoxyepinephrine, epinephrine, felypressin, indanazoline, metizoline, midodrine, naphazoline, nordefrin, octodrine, omipressin, oxymethazoline, phenylephrine, phenylethanolamine, phenylpropanolamine, propylhexedrine, pseudoephedrine, tetrahydrozoline, tramazoline, tuaminoheptane, tymazoline, vasopressin and xylometazoline.

In a further embodiment of the invention, the coating formulations and, hence, biocompatible coatings, can further include a biocompatible carrier. Examples of biocompatible carriers include human albumin, bioengineered human albumin, polyglutamic acid, polyaspartic acid, polyhistidine, pentosan polysulfate, polyamino acids, sucrose, trehalose, melezitose, raffinose and stachyose.

The thickness of the biocompatible coating disposed on the microprojections is preferably less than 50 microns. In one embodiment of the invention, the coating thickness is less than 25 microns.

The biocompatible coating provides a biologically effective amount of the nicotine-based agent and, if employed, a biologically effective amount of the vasoconstrictor.

The biocompatible coating can be applied to and dried on the microprojections using known coating methods. For example, the microprojections can be immersed or partially immersed into an aqueous coating solution. Alternatively, the coating solution can be sprayed onto the microprojections. Preferably, the spray has a droplet size of about 10-200 picoliters. More preferably, the droplet size and placement is precisely controlled using printing techniques so that the coating solution is deposited directly onto the microprojections and not onto other "non-piercing" portions of the member having the microprojections.

The method for transdermally delivering a nicotine-based agent to a nicotine user, in accordance with one embodiment of the invention, comprises the steps of (i) providing a microprojection member having a plurality of microprojections that are adapted to pierce the stratum corneum of the nicotine user, (ii) coating the microprojection member with a coating formulation having at least one nicotine-based agent to form a biocompatible coating and (iii) applying the microprojection member to the skin of the nicotine user, whereby the microprojection members pierce the stratum corneum of the nicotine user and deliver the biocompatible coating and, hence, nicotine-based agent disposed therein.

DETAILED DESCRIPTION OF THE INVENTION

The present invention, as described herein, provides an effective method and apparatus to reduce or eliminate an individual's tobacco or nicotine usage habit, particularly smoking, as well as the nicotine dependency associated with that habit. The reduction or elimination of tobacco usage is accomplished with or without behavioral intervention. Such a strategy expands the use of nicotine replacement therapy from an abrupt tobacco usage cessation to a gradual reduction. Gradually reducing the number of cigarettes smoked or other nicotine products used while replacing the nicotine with an alternative source, such as the coated microprojection member of the invention, aids in reducing nicotine cravings and withdrawal thereby facilitating reduction or elimination of tobacco usage.

As indicated above, the present invention comprises an apparatus and system for transdermal delivery of nicotine-based agents to a tobacco or nicotine user. The system generally includes a microprojection member having a microprojection array comprising a plurality of microprojections that are adapted to pierce through the stratum corneum into the underlying epidermis layer, or epidermis and dermis layers.

Preferably, the microprojections have a coating thereon that contains at least one biologically active agent, more preferably, a nicotine-based agent. Upon piercing through the stratum corneum layer of the skin, the agent-containing coating is dissolved by body fluid (intracellular fluids and extracellular fluids such as interstitial fluid) and released into the epidermis layer for systemic therapy (i.e., bolus delivery).

In contrast, in a conventional passive patch, the agent-containing coating must diffuse into and through the stratum corneum to achieve systemic delivery. Thus, such systems do not exhibit bolus delivery.

Preferably, release of the nicotine-based agent into the epidermis layer of the skin occurs within 1 hour following application of the microprojection array. More preferably, release of the nicotine-based agent into the epidermis layer occurs within 15 min following application of the microprojection array. Even more preferably, release of the nicotine-based agent into the epidermis layer occurs within 5 min following application of the microprojection array.

According to the invention, the kinetics of the coating dissolution and release will depend on many factors including the nature of the biologically active agent, the coating process, the coating thickness and the coating composition (e.g., the presence of coating formulation additives). Depending on the release kinetics profile, it may be necessary to maintain the coated microprojections in piercing relation with the skin for extended periods of time. This can be accomplished by anchoring the microprojection member to the skin using adhesives or by using anchored microprojections, such as described in PCT Publication WO 97/48440, which is incorporated by reference herein in its entirety.

Referring now to FIG. 1 (see Original Patent), there is shown one embodiment of a microprojection member 5 for use with the present invention. As illustrated in FIG. 1, the microprojection member 5 includes a microprojection array 7 having a plurality of microprojections 10. The microprojections 10 preferably extend at substantially a 90.degree. angle from the sheet 12, which includes openings 14.

According to the invention, the sheet 12 may be incorporated into a delivery patch, including a backing 15 for the sheet 12, and may additionally include adhesive 16 for adhering the patch to the skin (see FIG. 3 (see Original Patent)). In this embodiment, the microprojections 10 are formed by etching or punching a plurality of microprojections 10 from a thin metal sheet 12 and bending the microprojections 10 out of the plane of the sheet 12.

The microprojection member 5 can be manufactured from various metals, such as stainless steel, titanium, nickel titanium alloys, or similar biocompatible materials, such as polymeric materials. Preferably, the microprojection member 5 is manufactured out of titanium.

Microprojection members that can be employed with the present invention include, but are not limited to, the members disclosed in U.S. Pat. Nos. 6,083,196, 6,050,988 and 6,091,975, which are incorporated by reference herein in their entirety.

Other microprojection members that can be employed with the present invention include members formed by etching silicon using silicon chip etching techniques or by molding plastic using etched micro-molds, such as the members disclosed U.S. Pat. No. 5,879,326, which is incorporated by reference herein in its entirety.

Referring now to FIG. 2 (see Original Patent), there is shown the microprojection member 5 having microprojections 10 that include a biocompatible coating 16. According to the invention, the coating 16 can partially or completely cover each microprojection 10. For example, the coating 16 can be in a dry pattern coating on the microprojections 10. The coating 16 can also be applied before or after the microprojections 10 are formed.

According to the invention, the coating 16 can be applied to the microprojections 10 by a variety of known methods. Preferably, the coating is only applied to those portions the microprojection member 5 or microprojections 10 that pierce the skin (e.g., tips 18).

One such coating method comprises dip-coating. Dip-coating can be described as a means to coat the microprojections by partially or totally immersing the microprojections 10 into a coating solution. By use of a partial immersion technique, it is possible to limit the coating 16 to only the tips 18 of the microprojections 10.

A further coating method comprises roller coating, which employs a roller coating mechanism that similarly limits the coating 16 to the tips 18 of the microprojections 10. The roller coating method is disclosed in U.S. application Ser. No. 10/099,604 (Pub. No. 2002/0132054), which is incorporated by reference herein in its entirety.

As discussed in detail in the noted application, the disclosed roller coating method provides a smooth coating that is not easily dislodged from the microprojections 10 during skin piercing. The smooth cross-section of the microprojection tip coating is further illustrated in FIG. 2A (see Original Patent).

According to the invention, the microprojections 10 can further include means adapted to receive and/or enhance the volume of the coating 16, such as apertures (not shown), grooves (not shown), surface irregularities (not shown) or similar modifications, wherein the means provides increased surface area upon which a greater amount of coating can be deposited.

Another coating method that can be employed within the scope of the present invention comprises spray coating. According to the invention, spray coating can encompass formation of an aerosol suspension of the coating composition. In one embodiment, an aerosol suspension having a droplet size of about 10 to 200 picoliters is sprayed onto the microprojections 10 and then dried.

Pattern coating can also be employed to coat the microprojections 10. The pattern coating can be applied using a dispensing system for positioning the deposited liquid onto the microprojection surface. The quantity of the deposited liquid is preferably in the range of 0.1 to 20 nanoliters/microprojection. Examples of suitable precision-metered liquid dispensers are disclosed in U.S. Pat. Nos. 5,916,524; 5,743,960; 5,741,554; and 5,738,728; which are fully incorporated by reference herein.

Microprojection coating solutions can also be applied using ink jet technology using known solenoid valve dispensers, optional fluid motive means and positioning means which is generally controlled by use of an electric field. Other liquid dispensing technology from the printing industry or similar liquid dispensing technology known in the art can be used for applying the pattern coating of this invention.

According to the invention, the coating formulations applied to the microprojection member to form solid coatings can comprise aqueous and non-aqueous formulations having at least one nicotine-based agent. According to the invention, the active agent can be dissolved within a biocompatible carrier or suspended within the carrier.

Preferably, the nicotine-based agent comprises nicotine base, nicotine salts, and simple derivatives of nicotine. More preferably, the nicotine-based agent is a salt of nicotine.

There are several advantages related to the use of a salt instead of the base. First, use of a nicotine salt is expected to result in the reduction or elimination of skin depot as compared to nicotine base. Another advantage is that the salt form of nicotine is expected to result in improved nicotine chemical stability and improved stability of the chemical composition of the coating during storage as compared to nicotine base. A further advantage is that the salt form of nicotine is expected to reduce or eliminate the bad smell characteristic of nicotine base.

Examples of pharmaceutically acceptable nicotine salts include, but are not limited to, acetate, propionate, butyrate, pentanoate, hexanoate, heptanoate, levulinate, chloride, bromide, citrate, succinate, maleate, glycolate gluconate, glucuronate, 3-hydroxyisobutyrate, 2-hydroxyisobutyrate, lactate, malate, pyruvate, fumarate, tartarate, tartronate, nitrate, phosphate, benzene sulfonate, methane sulfonate, sulfate, sulfonate, salycilate and double salts such as zinc chloride.

Examples of simple nicotine derivatives include, but are not limited to, amides, carbamates, imines, enamines, and N-acyloxyalkyloxycarbonyls. Preferably these derivatives are reversible and will degrade or be metabolized to nicotine once introduced into the body.

Even more preferably, the nicotine-based agent is a salt of nicotine presenting low volatility. Use of this type of salts is expected to result in optimal stability of the chemical composition of the coating during storage. The solid coating is obtained by drying a formulation on the microprojection as described in U.S. patent application 2002/0128599. A number of factors affect the volatility of compounds. These include temperature, atmospheric pressure, and vapor pressure of the compound. The volatilization process is time dependant.

In addition, ionized compounds present a much lower volatility as compared to their unionized forms. For example, acetic acid presents a boiling point of 118.degree. C. while sodium acetate is essentially non-volatile. During the drying process, all volatiles, including water are mostly removed. If a volatile compound in equilibrium between its ionized and non-ionized forms is present in solution, only the non-ionized form disappears from the formulation at the time where the drying process takes place and the ionized form stays in solution.

In a solid coating on a microprojection array, the active agent is typically present in an amount of less than about 2 mg per unit dose. With the addition of excipients and counterions, the total mass of solid coating is less than 4 mg per unit dose.

The microprojection array is usually disposed on an adhesive backing, which is attached to a disposable polymeric retainer ring. This assembly is typically packaged individually in a pouch or a polymeric housing. In addition to the assembly, this package contains an atmosphere (usually inert) that represents a volume of at least 3 mL. This large volume (as compared to that of the coating) acts as a sink for any volatile component. For example, at 20.degree. C., the amount of acetic acid present in a 3 mL atmosphere as a result of its vapor pressure would be about 0.15 mg. This amount is typically what would be present in the solid coating if acetic acid were used as a counterion. In addition, components of the assembly such as the adhesive are likely to act as additional sinks for volatile components. As a result, during long-term storage, it is likely that the concentration of any volatile component present in the coating would change dramatically. These conditions are atypical of packaging of pharmaceutical compounds where large amounts of additives are usually present. Nicotine base also presents some volatility and, if present in the formulation, will likely be affected similarly by these processes.

Selection of a salt of nicotine presenting low volatility is based on the pKa of nicotine as well as the pKa and melting point of the acidic counterion. As is well known in the art, nicotine itself is a liquid at room temperature and presents some volatility. The smell of nicotine base is indeed very strong and this smell (which is partly due to volatile degradants) is greatly reduced by salification. Indeed most, if not all, nicotine salts present a higher melting point than nicotine itself. In addition, if nicotine salification is accomplished with an acidic compound having a pKa greater than about 4, a fraction of the acid and/or nicotine will be free and the counterion will slowly evaporate and/or migrate in system components, which will result in poor stability of the system. Examples of volatile counterions include, but are not limited to, acetic acid, propionic acid and butyric acid.

A most preferred embodiment is directed to nicotine salts with low volatility, wherein the counterion is a strong acid. A strong acid is defined as an acidic compound presenting at least one pKa lower than about 2. Examples of such acids include hydrochloric acid, hydrobromic acid, nitric acid, sulfonic acid, sulfuric acid, maleic acid, phosphoric acid, benzene sulfonic acid and methane sulfonic acid.

In another most preferred embodiment, the acidic counterion is a weak acid with low volatility. Such a compound is defined as an acidic compound presenting at least one pKa higher than about 2 and a melting point higher than about 50.degree. C. Examples of such acids include citric acid, succinic acid, glycolic acid, gluconic acid, glucuronic acid, lactic acid, malic acid, pyruvic acid, tartaric acid, tartronic acid, fumaric acid, and salycilic acid.

According to the invention, nicotine and the counterion can be combined in various stoichiometric amounts. Excess of counterion (as the free acid or as a salt) can be added to nicotine in order to control pH. Mixtures of different counterions can also be used.

The coating formulation containing a nicotine-based agent would be preferably aqueous-based. Following drying, as described in U.S. Patent Application 2002/0128599 (World publication WO02/094368), the formulation is substantially free of water, although residual water may be present at up to 10 wt %.

Optionally the nicotine-based agent could be formulated in non-aqueous formulations. Examples of solvents that could be used include ethanol, IPA, chloroform, ether, petroleum ether, kerosene, and other volatile solvents. Formulations additives (wetting agents, viscosity enhancing agents) can also be added to the formation. Following drying, the formulation is substantially free of volatile solvent although residual solvent may be present at up to 10 wt %.

The concentration of the nicotine-based agent in the coating formulation is preferably in the range of approximately 5-80 wt. %, more preferably, in the range of approximately 10-70 wt. %. Even more preferably, the concentration of the nicotine-based agent in the coating formulation is in the range of approximately 20-60 wt. % of the coating formulation.

The concentration of the nicotine-based agent in the solid coating(s) is preferably up to approximately 99 wt. %. More preferably, the concentration of the nicotine-based agent in the solid coating(s) is in the range of approximately 30-70 wt. %.

According to the invention, the nicotine-based agent used in the present invention requires that the total amount of the agent coated on the microprojections of a microprojection array be sufficient to effectively delivery in the range of approximately 0.02-2.0 mg of the agent to a nicotine user. According to the invention, amounts within this range can be coated onto a microprojection array of the type shown in FIG. 1 having an area of up to 10 cm.sup.2 and a microprojection density of up to 2000 microprojections per cm.sup.2.

According to the invention, the coating formulations preferably include at least one wetting agent. As is well known in the art, wetting agents can generally be described as amphiphilic molecules. When a solution containing the wetting agent is applied to a hydrophobic substrate, the hydrophobic groups of the molecule bind to the hydrophobic substrate, while the hydrophilic portion of the molecule stays in contact with water. As a result, the hydrophobic surface of the substrate is not coated with hydrophobic groups of the wetting agent, making it susceptible to wetting by the solvent. Wetting agents include surfactants as well as polymers presenting amphiphillic properties.

In one embodiment of the invention, the coating formulations include at least one surfactant. According to the invention, the surfactant(s) can be zwitterionic, amphoteric, cationic, anionic, or nonionic. Examples of surfactants include, sodium lauroamphoacetate, sodium dodecyl sulfate (SDS), cetylpyridinium chloride (CPC), dodecyltrimethyl ammonium chloride (TMAC), benzalkonium, chloride, polysorbates such as Tween 20 and Tween 80, other sorbitan derivatives such as sorbitan laurate, and alkoxylated alcohols such as laureth-4. Most preferred surfactants include Tween 20, Tween 80, and SDS.

Applicants have found that the use of the noted surfactants in the desired ranges provides maximum wetting at and above the critical micelle concentration (CMC). Wetting is also noticeable at concentrations as low as about one order of magnitude below the CMC.

Preferably, the concentration of the surfactant is in the range of approximately 0.001-2 wt. % of the coating solution formulation.

In a further embodiment of the invention, the coating formulations include at least one polymeric material or polymer that has amphiphilic properties. Examples of the noted polymers include, without limitation, cellulose derivatives, such as hydroxyethylcellulose (HEC), hydroxypropylmethylcellulose (HPMC), hydroxypropycellulose (HPC), methylcellulose (MC), hydroxyethylmethylcellulose (HEMC), or ethylhydroxyethylcellulose (EHEC), as well as pluronics.

In one embodiment of the invention, the concentration of the polymer presenting amphiphilic properties is preferably in the range of approximately 0.01-20 wt. %, more preferably, in the range of approximately 0.03-10 wt. % of the coating formulation. Even more preferably, the concentration of the wetting agent is in the range of approximately 0.1-5 wt. % of the coating formulation.

As will be appreciated by one having ordinary skill in the art, the noted wetting agents can be used separately or in combinations.

According to the invention, the coating formulations can further include a hydrophilic polymer. Preferably the hydrophilic polymer is selected from the following group: poly(vinyl alcohol), poly(ethylene oxide), poly(2-hydroxyethylmethacrylate), poly(n-vinyl pyrolidone), polyethylene glycol and mixtures thereof, and like polymers. As is well known in the art, the noted polymers increase viscosity.

The concentration of the hydrophilic polymer in the coating formulation is preferably in the range of approximately 0.01-20 wt. %, more preferably, in the range of approximately 0.03-10 wt. % of the coating formulation. Even more preferably, the concentration of the wetting agent is in the range of approximately 0.1-5 wt. % of the coating formulation.

According to the invention, the coating formulations can further include a biocompatible carrier such as those disclosed in Co-Pending U.S. application Ser. No. 10/127,108, which is incorporated by reference herein in its entirety. Examples of biocompatible carriers include human albumin, bioengineered human albumin, polyglutamic acid, polyaspartic acid, polyhistidine, pentosan polysulfate, polyamino acids, sucrose, trehalose, melezitose, raffinose and stachyose.

The concentration of the biocompatible carrier in the coating formulation is preferably in the range of approximately 2-70 wt. %, more preferably, in the range of approximately 5-50 wt. % of the coating formulation. Even more preferably, the concentration of the wetting agent is in the range of approximately 10-40 wt. % of the coating formulation.

The coatings of the invention can further include a vasoconstrictor such as those disclosed in Co-Pending U.S. application Ser. Nos. 10/674,626 and 60/514,433, which are incorporated by reference herein in their entirety. As set forth in the noted Co-Pending Applications, the vasoconstrictor is used to control bleeding during and after application on the microprojection member. Preferred vasoconstrictors include, but are not limited to, amidephrine, cafaminol, cyclopentamine, deoxyepinephrine, epinephrine, felypressin, indanazoline, metizoline, midodrine, naphazoline, nordefrin, octodrine, ornipressin, oxymethazoline, phenylephrine, phenylethanolamine, phenylpropanolamine, propylhexedrine, pseudoephedrine, tetrahydrozoline, tramazoline, tuaminoheptane, tymazoline, vasopressin, xylometazoline and the mixtures thereof. The most preferred vasoconstrictors include epinephrine, naphazoline, tetrahydrozoline indanazoline, metizoline, tramazoline, tymazoline, oxymetazoline and xylometazoline.

The concentration of the vasoconstrictor, if employed, is preferably in the range of approximately 0.1 wt. % to 10 wt. % of the coating.

In yet another embodiment of the invention, the coating formulations include at least one "pathway patency modulator", such as those disclosed in Co-Pending U.S. application Ser. No. 09/950,436, which is incorporated by reference herein in its entirety. As set forth in the noted Co-Pending Application, the pathway patency modulators prevent or diminish the skin's natural healing processes thereby preventing the closure of the pathways or microslits formed in the stratum corneum by the microprojection member array. Examples of pathway patency modulators include, without limitation, osmotic agents (e.g., sodium chloride), and zwitterionic compounds (e.g., amino acids).

The term "pathway patency modulator", as defined in the Co-Pending Application, further includes anti-inflammatory agents, such as betamethasone 21-phosphate disodium salt, triamcinolone acetonide 21-disodium phosphate, hydrocortamate hydrochloride, hydrocortisone 21-phosphate disodium salt, methylprednisolone 21-phosphate disodium salt, methylprednisolone 21-succinaate sodium salt, paramethasone disodium phosphate and prednisolone 21-succinate sodium salt, and anticoagulants, such as citric acid, citrate salts (e.g., sodium citrate), dextrin sulfate sodium, aspirin and EDTA.

According to the invention, the coating formulations can also include a non-aqueous solvent, such as ethanol, chloroform, ether, propylene glycol, polyethylene glycol and the like, dyes, pigments, inert fillers, permeation enhancers, excipients, and other conventional components of pharmaceutical products or transdermal devices known in the art.

Other known formulation adjuvants can also be added to the coating formulations as long as they do not adversely affect the necessary solubility and viscosity characteristics of the coating formulation and the physical integrity of the dried coating.

Preferably, the coating formulations have a viscosity less than approximately 500 centipoise and greater than 3 centipoise in order to effectively coat each microprojection 10. More preferably, the coating formulations have a viscosity in the range of approximately 3-200 centipoise.

According to the invention, the desired coating thickness is dependent upon the density of the microprojections per unit area of the sheet and the viscosity and concentration of the coating composition as well as the coating method chosen. Preferably, the coating thickness is less than 50 microns.

In one embodiment, the coating thickness is less than 25 microns, more preferably, less than 10 microns as measured from the microprojection surface. Even more preferably, the coating thickness is in the range of approximately 1 to 10 microns.

In all cases, after a coating has been applied, the coating formulation is dried onto the microprojections 10 by various means. In a preferred embodiment of the invention, the coated member 5 is dried in ambient room conditions. However, various temperatures and humidity levels can be used to dry the coating formulation onto the microprojections. Additionally, the coated member 5 can be heated, lyophilized, freeze dried or similar techniques used to remove the water from the coating.

Referring now to FIGS. 4 and 5 (see Original Patent), for storage and application, the microprojection member 5 is preferably suspended in a retainer ring 40 by adhesive tabs 6, as described in detail in Co-Pending U.S. application Ser. No. 09/976,762 (Pub. No. 2002/0091357), which is incorporated by reference herein in its entirety.

After placement of the microprojection member 5 in the retainer ring 40, the microprojection member 5 is applied to the patient's skin. Preferably, the microprojection member 5 is applied to the skin using an impact applicator, such as disclosed in Co-Pending U.S. application Ser. No. 09/976,798, which is incorporated by reference herein in its entirety.

As will be appreciated by one having ordinary skill in the art, the present invention can also be employed with the transdermal drug delivery system and apparatus disclosed in Co-Pending Application No. 60/514,433.
 

Claim 1 of 18 Claims

1. An apparatus for transdermally delivering nicotine-based agents to a nicotine user, comprising a microprojection member having a plurality of microprojections that are adapted to pierce said nicotine user's stratum corneum for bolus delivery of at least one nicotine-based agent, said microprojection member including a biocompatible coating having at least one nicotine-based agent; wherein a total amount of the nicotine-based agent coated on the microprojections is sufficient to effectively deliver in the range of approximately 0.02-2.0 mg of the agent to the nicotine user, and wherein the composition of the coating is selected to deliver at least 50% of the total amount of the nicotine-based agent coated on the microprojection into the skin of the user one hour or less following application of the microprojection member to the user's skin.
 

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.