Patent Description:
One modality for administering therapeutic medicaments is by dermal application with subsequent transdermal absorption. This is quite common for hormone therapy, but is also used for pain medications and corticosteroids, among others. The therapeutic agent is typically blended into a carrier cream that is then rubbed onto the skin. Often, the formulation must be individualized for each consumer based on prescribed medicaments and dosages. These formulations are often prepared in compounding pharmacies, who then also prepare a container filled with the formulation and give it to the consumer. These containers are dispensers of various kinds, for example syringes or pump dispensers.

Dispensing devices called propel/repel containers are common commercially available items used for cosmetics such as lip balm, lipstick, deodorants, antiperspirants, and moisturizers, and also for household and industrial products such as glue and lubricants. These have been adapted for topical application of therapeutic agents.

One of the most common configurations of propel/repel container features a hollow cylinder with a movable floor, female threads formed in the floor, a male-threaded rod passing through the female threads, and a screw knob, integral with the male-threaded rod, captured on one end of the cylinder. The product to be dispensed resides in the cylinder above the elevator. Turning the screw knob one direction forces the elevator upward, propelling the product from the cylinder, with the other direction repelling it. <CIT> to Becker discloses an example propel/repel container of this configuration, in this case for solid or semi-solid products like lipstick.

<CIT>adds a closed exit end with an exit hole or holes, making it suitable for liquids and gels. <CIT> adds a ratchet mechanism to prevent repel motion, making it a propel dispenser only. <CIT> shows a configuration in which the drive screw is disposed entirely outside of the product reservoir, making the reservoir a simple, empty cylinder. <CIT> discloses a one-way ratchet mechanism as well as audible and tactile signals that are tied to metered incremental doses, called clicks, related to the volume of product dispensed.

In the prior art, one set of devices for compounding liquids, creams, and gels for pharmaceutical formulations is disclosed in <CIT>and <CIT>. Devices based on these technologies are offered by GAKO® International GmbH, and include motorized mixing machines, called an electronic mortar and pestle, like their Unguator® line. These also include various mixing jars and related components needed for the compounding operations. According to the company's literature, its mixing jars serve as "measuring unit, mixing chamber, storage container, and dispensing jar.

Topical applicators for pharmaceutical formulations of liquids, creams, and gels with dose metering features also exist in the prior art. Examples of these devices are disclosed in <CIT> and <CIT>, and <CIT>. These are propel/repel containers of conventional construction with the additions of an indexed dose metering capability, ratchet mechanisms to prevent repel, and audible and tactile dose indicators. These are commercially available as the Topi-CLICK® from DoseLogix and the Ticker™ Transdermal Applicator from BIOSRX, respectively.

The prior art has several drawbacks. Currently available metered dose topical applicators are not suitable as mixing jars for a variety of reasons. For example, because of their internal geometry and internal drive screw, "dead zones" exist that inhibit homogeneous mixing. Therefore, the pharmaceutical formulation must first be compounded separately, which is often done in special jars using the aforementioned electronic mortar and pestle machines, then transferred from the jar into the topical applicator. This is time consuming, messy, and clumsy for pharmacy technicians, who must somehow painstakingly clean the formulation from the mixing jar and mixing blade using spatulas. Furthermore, because the prior art metered dose topical applicators have drive screws within their reservoirs, filling the reservoir is inconvenient, especially with thick creams. Considerable skill is required to avoid trapping air pockets and contaminating the exterior of the topical applicator.

Moreover, once the compounded formulation is transferred into the topical applicator, the excess space needs to be removed, that is, the air must be purged from the reservoir. But because the container is supplied with the elevator fully withdrawn (i.e. reservoir empty), the purge operation often requires many revolutions of the dosing knob. This is especially true if the topical applicator is only partially filled with the formulation, which is a common situation. This is time consuming and inconvenient for pharmacy technicians.

Although the compounding jars in the prior art, specifically those from GAKO® International GmbH, for example, can be used as dispensers when combined with the threaded "spindle" that company provides, these lack suitable metering, indexing, and applicator features. Thus, they are, practically speaking, only suitable as transfer dispensers from the mixing jar itself to a bona fide topical applicator.

Included in the prior art for medication dispensers are numerous examples of dispensers prefilled during initial manufacturing with therapeutic agents. One such example is disclosed in <CIT>.

<CIT> describes a dispenser for fluid materials, such as cosmetic products, having a hollow housing to store the product. <CIT> shows a dispenser for a cream, gel or soft solid composition, and <CIT> refers to a visual, bi-audible, and bi-tactile metered-dose transdermal medicament applicator.

In light of the drawbacks of the prior art, there exists a need for improved methods of supplying, preparing, and using metered dose topical applicators that avoid transferring formulation components from bulk containers to mixing containers and from mixing containers to a dosing applicators, and that hastens and simplifies the preparation process.

A device for incrementally metering discrete volumes of a compounded pharmaceutical liquid, cream, or gel formulation, and for topically applying the formulation for dermal absorption is configured to allow compounding, for example using an electronic mortar and pestle, directly in the device, thus avoiding the need to transfer compounded formulations from mixing vessels to separate dispensers or applicators.

Embodiments may also feature a metered dose topical applicator device wherein the device is prefilled with a cream or gel carrier fluid, thus avoiding the need to transfer the carrier fluid into the applicator during medicament compounding.

Embodiments may also feature a metered dose topical applicator device wherein the device has been prefilled, during initial production, with pharmaceutical medicament formulations, thus avoiding altogether the need for further mixing and preparation by compounding pharmacies.

Embodiments can also include additional advantageous features as described in the following:
In embodiments a means to reversibly connect the device to a mixing apparatus, such as an electronic mortar and pestle that includes a mixing paddle, for compounding and mixing directly in the device and then a means for attaching a dispense cap with one or more dispense apertures that is secured on the barrel and is not readily removable by the consumer. For example, the barrel may have threads or other features that allow a rotational attachment to the mixing apparatus by rotating the barrel in one direction for attachment and rotating the barrel in an opposite direction for detachment. A lip or other protrusion or may extend circumferentially around the barrel just below the threats or other features, the lip or other protrusions may receive cooperating snap on features on the dispense cap to lock the cap in place as it is pressed on so that it is not readily removable without tools or without damaging the device. In embodiments, a circumferential recess or recesses around the barrel may receive projections positioned and sized to interface with the circumferential recess or recesses. In embodiments, different dispense caps, such as with different number of apertures or differently sized apertures for particular applications may be supplied to a compounder, for example a pharmacy, for selection of an appropriate dispense cap.

A cap for the device with a plurality of openings facilitates purging of air and allows outflow of the formulation, and to provide a means of hands-free topical application of the formulation.

Means of propelling the formulation out of the device through the cap are realized in form of an elevator driven by a drive mechanism comprising a screw thread and drive nut, which, in turn, can be actuated by user action through rotating a knob.

An override of the propelling allows rapid advance of the elevator, thereby hastening the purging of air from the device. Means can include a tool configured as a rod or tubular device to axially push the elevator and cause slippage of rotating screw nut fingers engaging threads of a non-rotating threaded drive shaft to extend the elevator upwardly. In embodiments, the threaded rod or an extension thereto may extend below the container housing. In embodiments where the threaded shaft rotates and extends through the elevator, and the elevator has threaded portions that cooperate with the rotatable threaded drive shaft, the threaded portions may be configured to allow slippage on the drive shaft permitting a member, such as an elongate tool, to access the container and push the elevator upwardly. An opening in the bottom of the container allows axial access to the interior of the container and the elevator or a member connected to the elevator.

In embodiments, a dispensing device has a surface dispense area of at least <NUM>,<NUM><NUM> (. In embodiments, the surface dispense area is at least <NUM>,<NUM><NUM> (<NUM> square inch). In embodiments, the surface dispense area is at least <NUM>,<NUM><NUM> (<NUM> square inches). In embodiments, the capacity of the container for holding the pharmaceutical formulation is at least <NUM>. In embodiments, the capacity of the container is at least <NUM>.

A feature and advantage of embodiments is that the components may be readily manufactured by conventional injection molding techniques and readily assembled manually or robotically. A nut engaged with a threaded rod may be configured with spring fingers to allow a one-way slippage of the rod with respect to the nut. The nut can connected to a manually rotatable knob in an embodiment to rotate with the knob. In an embodiment, the nut may be non-rotatable with respect to the elevator and a rotatable threaded rod is rotated by way of a knob.

In embodiments, the nut can have flexible fingers with threaded portions at one end, a tubular mid portion and a cooperating ratchet portion at an opposing end. The cooperating ratchet portion may comprise a plurality of detent portions that engage recesses or openings in a surface of the container housing. In embodiments, the recesses or openings may be positioned on a plate unitary with a barrel portion of the container housing and may provide audible and/or tactile indication of incremental rotations corresponding to indexed metered doses.

Embodiments can include an indexing means that partitions the propelled formulation into metered doses.

Embodiments can include audible and tactile indications corresponding to the indexed metered doses.

Embodiments can include a one-way, or ratcheting, mechanism to prevent reversing of the propel action (repel).

Embodiments can include other useful features such as volumetric or other measurement scales, protective covers, and ergonomic geometric elements.

A further feature and advantage of the invention is that of a container housing configured as a barrel and elevator defining a reservoir that is conducive of holding a wide range of volumes of a compounded pharmaceutical liquid, cream, or gel formulation without needing a time consuming rotational adjustment of a knob to move the elevator toward the cap thereby bringing the liquid, cream, or gel formulation to the dispense cap.

A feature and advantage is that the adjustment needs to be performed once with a tool that may be readily discarded. In other embodiments an extension of a threaded rod threadably engaged with a nut and connecting to the elevator may be pushed upwardly raising the elevator.

Persons of ordinary skill in the relevant arts will recognize that various embodiments can comprise fewer features than illustrated in any individual embodiment described above. The embodiments described herein are not meant to be an exhaustive presentation of the ways in which the various features may be combined. Accordingly, the embodiments are not mutually exclusive combinations of features; rather, the claims can comprise a combination of different individual features selected from different individual embodiments, as understood by persons of ordinary skill in the art. The above disclosure is related to the detailed technical contents and features. People skilled in this field may proceed with a variety of modifications and replacements based on the disclosures and suggestions as described within the scope of the claims. While this disclosure is amenable to various modifications and alternative forms, specifics thereof are shown by way of example in the drawings and described in detail.

Referring to <FIG>, a metered dose topical applicator <NUM> in accordance with the present invention is shown. The applicator <NUM> includes a housing configured as a barrel <NUM>, an actuating knob <NUM>, and an applicator cap <NUM>, which includes a plurality of exit holes <NUM>. Rotating actuator knob <NUM> effects collapse of a medicament reservoir within barrel <NUM>, which results in expulsion of a pharmaceutical cream formulation, which is stored in the reservoir, through exit holes <NUM>, all of which will be explained in full detail below.

Turning to <FIG>, these show how the component parts of metered dose topical applicator <NUM> are arranged and assembled. A housing configured as a barrel <NUM> accepts actuating knob <NUM> into its lower end <NUM>, and a drive nut <NUM> into its upper end <NUM>. Actuating knob <NUM> includes a handle portion, <NUM>, a central axially extending tube shaped knob axle <NUM>, with an exterior surface <NUM> upon on which snap lugs <NUM> are formed, and an end plate <NUM>. Apertures <NUM> in the end plate may facilitate molding the snap lugs. Knob axle <NUM> inserts into, and is radially constrained by, bearing hole <NUM> in the mostly closed lower end <NUM> with the lower wall configured as lower end flange <NUM> of barrel <NUM>.

Drive nut <NUM> has snap slots <NUM> and, being substantially hollow, can insert onto knob axle <NUM>. Snap lugs <NUM> mate with snap slots <NUM> to irreversibly fix drive nut <NUM> and actuating knob <NUM> together, and further capturing both to barrel <NUM> in the axial direction, yet allowing rotation of the assembled drive nut <NUM> and actuating knob <NUM> relative to barrel <NUM>.

Drive nut <NUM> also includes ratchet arms <NUM>. The function and structure of ratchet arms <NUM> is explained in detail below, but their basic purposes are <NUM>) to prevent reverse rotation of actuator knob <NUM>, turning the present embodiment into a propel only device, and <NUM>) to provide tactile and audible feedback to the user during rotation of actuator knob <NUM>.

The drive nut <NUM> may also include thread fingers <NUM>, whose complete function will be explained in detail below, but that assemble by screwing onto drive screw <NUM>. Drive screw <NUM> includes an end pin <NUM>, which non-rotatably inserts into elevator <NUM>, specifically into center hole <NUM> of elevator <NUM>, making an assembly that, when assembled functions as a single component. Note that <FIG> shows drive screw <NUM> and elevator <NUM> in the mated position.

Applicator cap <NUM> fits onto barrel <NUM> at its open end <NUM>, and is permanently retained by a snap fit created by the interfacing of cap snap lugs <NUM> of applicator cap <NUM> and retaining flange <NUM> of barrel <NUM>.

Protective cover <NUM> is removably affixed to applicator cap <NUM> via friction or, alternatively, an undercut snap fit (not shown).

Referring now to <FIG>, the metered dose topical applicator <NUM> is shown in a preassembled state ready to be filled with pharmaceutical formulation constituents. Barrel <NUM> includes upper end <NUM>, which is open to allow addition of the formulation constituents. Barrel <NUM> also includes a substantially cylindrical barrel wall <NUM>, with an inner surface <NUM>. The lower end <NUM> is mostly closed with a wall <NUM>.

Elevator <NUM> includes a seal lip <NUM>, which sealingly contacts barrel inner wall <NUM>, and an elevator face <NUM>. As previously described, drive screw <NUM> has been affixed to elevator <NUM>, making the end surface of end pin <NUM> equi-planar with elevator face <NUM>. Barrel inner surface <NUM>, seal lip <NUM>, and elevator face <NUM> (with endpin <NUM>) define a reservoir <NUM>, which is collapsible, as will be described later.

Still referring to <FIG>, thread fingers <NUM> of drive nut <NUM> are engaged with the drive threads <NUM> of drive screw <NUM>, and also in close proximity to elevator <NUM>. Drive nut <NUM> rests on the inside face <NUM> of the barrel lower end flange <NUM>. Actuator knob <NUM> rests against the outside face <NUM> of lower end flange <NUM>, and is immovably secured to drive nut <NUM> by mechanical interaction of snap lugs <NUM> and snap slots <NUM>. As previously described, actuator knob <NUM> is radially constrained in barrel <NUM> by the knob axle <NUM> fitting with bearing hole <NUM>. Thus, actuating knob is free to rotate relative to the main axis of barrel <NUM>, but otherwise constrained to it, as is drive nut <NUM>, with the result that rotating actuating knob <NUM> rotates the drive nut and moves drive screw <NUM> axially and, in turn, elevator <NUM>, which are fixed together, in an axial direction, resulting in a volumetric change to reservoir <NUM>.

The drive nut and drive screw constitute one configuration of an elevating mechanism <NUM>. Other drive mechanisms may also be suitable.

The metered dose topical applicator <NUM> described above and shown in <FIG> is shown in <FIG> in a state ready to be filled with pharmaceutical formulation constituents. A typical formulation will include a base material such as a suitable liquid, gel, or cream, and may also include therapeutic agents such as, for example, hormones, pain medications, or corticosteroids. Other non-therapeutic additives may also be included such as, for example, an anti-foaming agent like simethicone. The person preparing the metered dose topical applicator <NUM> for subsequent use by an end consumer will load the prescribed constituents into reservoir <NUM> of metered dose topical applicator <NUM>, which can be used as a container for mixing them into a homogeneous formulation.

Creams and gels suitable for use as a base material in compounding with topically-applied medicaments are manufactured in numerous variations. There are typically oil-in-water emulsions akin to ordinary cosmetic moisturizers and vanishing creams. These may include any number of additives, including emulsifiers, anti-foaming agents such as simethicone, skin penetration enhancers, medicament stabilizers, anti-oxidants, buffers, and so on. Some example products that are commonly used, for example, for hormone replacement therapy are HRT Supreme Cream Base manufactured by Fagron, Inc. and HRT BOTANICALtm manufactured by Humco. Most are supplied to compounding pharmacies in tubs of various sizes, from <NUM> grams to <NUM> kilograms.

Referring to <FIG>, medicament <NUM> and carrier <NUM> are added to the topical applicator <NUM> into upper end <NUM> of barrel <NUM>. As needed, mixing supplement <NUM>, such as an anti-foaming agent like simethicone, may also be added.

Referring again briefly back to <FIG>, barrel <NUM> also includes barrel threads <NUM>, which are one example method of temporarily attaching a lid to enclose reservoir <NUM>.

One such lid is mixing cap <NUM> as shown in <FIG>. Mixing cap <NUM>, mixing blade <NUM>, and mixing shank <NUM> are example representations of components included in a typical electronic mortar and pestle (EMP machine), an example of which is an Unguator® PRO sold by GAKO® International GmbH. Mixing cap <NUM> includes interior female threads (not shown) that mate with barrel threads <NUM>, which mating forms a seal between mixing cap <NUM> and barrel upper end <NUM>. Mixing cap <NUM> includes mixing cap collar <NUM>, on which mixing cap threads <NUM> are formed. Mixing cap <NUM> can then be attached to a mixing apparatus such as the aforementioned Unguator® mixer via mixing cap collar <NUM> and mixing cap threads <NUM>. Mixing cap collar <NUM> also includes an internal seal (not shown) that seals against mixing shank <NUM>. An agitator such as mixing paddle <NUM> is permanently or removably attached to mixing shank <NUM>. Mixing shank <NUM> inserts into the electronic mortar and pestle machine, which can be programmed to rotate and translate mixing shank <NUM> and, thus, mixing paddle <NUM> within reservoir <NUM>, thereby mixing the contents therein.

Referring to <FIG>, once mixing cap <NUM> is screwed onto barrel <NUM>, topical applicator <NUM>, with to-be-mixed formulation constituents inside, is attached to mixing apparatus <NUM> by inserting mixing cap collar <NUM> into threaded receptacle <NUM> of translating arm <NUM> in the direction shown.

<FIG> shows topical applicator <NUM> being threaded into threaded receptacle <NUM> of translating arm <NUM>. Mixing shank <NUM> inserts into mixing apparatus <NUM> by automatic translation of translating arm <NUM>. Mixing apparatus <NUM> can then be programmed and started to effect mixing of the formulation constituents by both rotation of mixing paddle <NUM> (see <FIG>) and translation of translating arm <NUM>. The applicator may also be utilized with hand held mixing apparatus, not shown.

<FIG> shows a mixed formulation104 within reservoir <NUM> of metered dose topical applicator <NUM>. Applicator cap <NUM> has been affixed to barrel <NUM>, which captures formulation <NUM> within reservoir <NUM>.

Referring to <FIG>, barrel <NUM> includes retaining flange <NUM>, which interferes with cap snap lugs <NUM> during assembly of applicator cap <NUM> onto barrel <NUM>, producing a snap-fit retention of applicator cap <NUM> in its final position. Applicator cap <NUM> also includes cap seal lip <NUM>, which contacts barrel upper end <NUM> to effect a seal to close and define reservoir <NUM>. However, despite the need to create a seal to prevent the contained formulation <NUM> from exiting at this junction, it is not imperative that this seal be airtight. Allowing air, but not formulation <NUM>, to pass can be advantageous seal performance, facilitating purging of air out of reservoir <NUM> at this location. Because of the enormous difference in resistance to flow between air and typical topical creams, allowing air, but not cream, to pass is only a matter of a fashioning a suitable tortuous flow path or paths, which can be created in various ways.

Referring now to <FIG> and <FIG>, different embodiments of the metered dose topical applicators <NUM>, <NUM>' have been purged of air from their reservoirs, leaving only mixed formulation <NUM>. This purging may be achieved by advancing elevator <NUM> in different ways. First, a tool or purge rod <NUM> configured as an elongate member may be inserted into actuator knob <NUM> through the included purge access hole <NUM>, and then be used to push the lower end of drive screw <NUM>, which will advance elevator <NUM>. This is a means for a fast purge, and works by forcing the drive threads <NUM> to jump or slip their engagement with thread fingers <NUM>, in one direction only, which is explained with reference to <FIG>.

Drive nut <NUM> includes releasable thread engagement by way of thread fingers <NUM> on which internal nut thread <NUM> is formed. In this embodiment, there is a single thread tooth created with one helical revolution, but other thread configurations can be employed. In this embodiment, nut thread <NUM> is interrupted by cutting away relief slots <NUM>, in this case four. This creates thread fingers <NUM>, and allows them to flex outward and to slip and to disengage with drive threads <NUM> when an axial force is applied to drive screw <NUM> from below, as oriented in <FIG>. Nonetheless, when axial force is applied from above, as oriented in <FIG>, thread fingers <NUM> return to or remain in their normal position, and jam the nut threads <NUM> into drive threads <NUM>, ensuring engagement in this direction.

Referring to <FIG>, another way of purging air is illustrated. An extension <NUM> of the drive screw <NUM>' may protrude outwardly from the barrel or housing <NUM>'. In embodiments the extension may be separable, such as by breakage, from the drive screw <NUM>" after the air is purged from the reservoir.

Referring to <FIG>, in this embodiment the drive screw <NUM>" is fixedly attached to the rotatable actuator knob <NUM>". The nut is non-rotatably attached to the elevator <NUM>" and is disengageably connected to the threaded drive nut <NUM>" as described above. A U-shaped member <NUM> may be inserted into openings <NUM> to engage with the elevator or connected structure such as portions of the nut <NUM>" to urge the elevator upwardly by causing slippage of the drive nut and drive screw <NUM>" to purge the reservoir of air.

<FIG> shows the embodiment of <FIG> after use and empty of the mixed formulation <NUM>".

Referring now to <FIG>, a way of purging air from a reservoir <NUM> is by rotating actuator knob <NUM>, which is also the normal way of advancing elevator <NUM> to expel the contents of reservoir <NUM> through exit holes <NUM>.

Rotating actuator knob <NUM> also rotates drive nut <NUM> in the same direction, they being fixed to each other as previously described. Due to friction between barrel inner surface <NUM> and seal lip <NUM>, elevator <NUM> and drive screw <NUM> cannot rotate, they being fixed together as previously described. The result, then, is the axial displacement of elevator <NUM>, affecting the volume of reservoir <NUM>. In an embodiment, left-handed threads are used so that rotating actuator knob <NUM> in the direction shown in <FIG> results in upward translation of elevator <NUM>, thus conforming to the common right-hand screw convention for advancing screw thread mechanisms.

With rotation of actuator knob <NUM> as shown, contents of reservoir <NUM>, typically a mixed formulation <NUM> (not shown), having no other exit path, will be expelled through exit holes <NUM>. Applicator surface <NUM> of applicator cap <NUM> can then be used to rub the formulation onto the skin.

Barrel <NUM> can include a volumetric or other suitable status scale <NUM>, an example of which is shown in <FIG>. One embodiment of topical applicator <NUM> can accept <NUM> milliliters of mixed formulation <NUM>, and with additional head space volume in reservoir <NUM>. Other embodiments with larger or smaller volumes, and with corresponding scales can be construed as well.

The numbers and lines of scale <NUM> are read through barrel wall <NUM>, which can be suitably transparent or translucent, using indicator bar <NUM> of elevator <NUM>. Indicator bar <NUM> can be distinguishable, for example, by selectively applying ink. In this embodiment, the scale is milliliters, but any suitable or desired metered dose increments can be marked, including full or partial revolutions of actuator knob <NUM>.

In one embodiment of the metered dose topical applicator <NUM>, elevator <NUM> can only be advanced, which direction is called propel, and cannot be retracted, called repel, one means of which is described immediately below. This one-way movement facilitates accurate, unambiguous metering of the contents of reservoir <NUM>.

Referring now to <FIG>, drive nut <NUM> can include ratchet arms <NUM> on which ratchet arm extensions <NUM> are formed. <FIG> shows these in isolation. As shown in <FIG>, and in isolation in <FIG>, barrel <NUM> can include indentations or apertures defining ratchet slots <NUM> formed on the inside surface of lower end flange <NUM>. One side of ratchet slots <NUM> can include a slot ramp <NUM>, the opposite side an orthogonal face <NUM>. Drive nut <NUM> is made from a spring-like flexible material, such as, for example, injection molded polypropylene, acetal, or polyester, therefore making ratchet arms <NUM> also spring-like. In a first assembled position as shown in <FIG>, ratchet arm extensions <NUM> nest in ratchet slots <NUM>, and create a detent action. Moreover, because ratchet arms <NUM> also include ratchet arm stops <NUM>, which are orthogonal surfaces, rotation in the reverse direction (corresponding to that shown in <FIG>) is prevented by the abutting of ratchet arm stops <NUM> and the orthogonal face <NUM> of ratchet slot <NUM>.

But rotation of actuator knob <NUM> in the forward direction simultaneously rotates drive nut <NUM>, causing ratchet arms <NUM> to flex upwards as ratchet arm ramps <NUM> climb up slot ramps <NUM>. Continuing the aforesaid rotation, in this case for one-quarter turn, results in each ratchet arm extension <NUM> dropping into the next ratchet slot <NUM>. In this way, forward rotation of actuator knob <NUM> is indexed from one unambiguous position to the next, which can correspond to an accurately metered dose of mixed formulation <NUM>.

Embodiments illustrated employ four ratchet arms <NUM> and four ratchet slots <NUM>, resulting in indexed positions being one-quarter turn from each other, the rotational fraction per indexed position can, of course, be configured differently. Moreover, by selecting the number of index positions, the cross-sectional area of barrel <NUM>, and the lead of drive threads <NUM>, any required metered dose can be expelled with each indexed motion of actuator knob <NUM>. One embodiment, for example, expels <NUM> milliliters per indexed advancement of actuator knob <NUM>.

When ratchet arm extensions <NUM> drop into ratchet slots <NUM>, audible and tactile indication is given to the operator. This, in part, is because the drop is abrupt due to the orthogonal configurations of the trailing edge and leading edge of the ratchet arm extensions <NUM> and ratchet slots <NUM>, respectively, which generates noise and sensation from the impact of ratchet arms <NUM> with lower end flange <NUM>. Furthermore, the detent force created by the aforementioned nesting suggests a clear tactile stop for the operator. In addition, owing to the angles of the ratchet arm ramps <NUM> and corresponding slot ramps <NUM>, initiating rotational motion requires a larger torque than that required once the ratchet arm extensions <NUM> are moved out of ratchet slots <NUM>. This torque reduction naturally encourages the user to continue rotating actuator knob <NUM> until the next indexed position is reached. To assist the user further, barrel <NUM> can include barrel index indicators <NUM>, and actuator knob <NUM> can include knob index indicators <NUM>, examples of which are shown in <FIG>. These align in indexed positions, providing a visual cue to the operator, and can, of course, be configured in numerous ways.

Referring to <FIG>, applicator cap <NUM> includes a plurality of exit holes <NUM>, and an applicator surface <NUM>. Upon indexed advancement of actuator knob <NUM> mixed formulation <NUM> exits through exit holes <NUM>, and pools on applicator surface <NUM> (shown here at only one location). Mixed formulation <NUM> can then be applied and spread on the skin.

The metered dose topical applicator can include five exit holes <NUM>, but the number, size, and configuration can be adjusted to accomplish various purposes. For example, having more, rather than fewer, can facilitate purging of air from reservoir <NUM> by venting pockets of trapped air resting on the inside of applicator cap <NUM>. Small diameter holes can likewise facilitate this purging because air will still pass through small holes easily, but creams, with their much higher viscosity, will flow much slower through small holes, preferentially forcing out air until cream reaches all holes. On the other hand, larger holes advantageously facilitate the egress of creams, resulting in a more rapid outflow with a lower tendency to "weep," because internal pressure is more rapidly relieved by faster flow of cream. Also, exit holes <NUM> can include exit chamfers <NUM>, which can advantageously store minute amounts of cream that might exit the metered dose applicator device after application is complete, preventing it from smearing onto other contacting surfaces.

Referring to <FIG>, the metered dose topical applicator <NUM> can include a protective cover <NUM>. In this figure, metered dose topical applicator <NUM> is shown in the spent position wherein reservoir <NUM> is fully collapsed and its contents substantially expelled. As shown, the inside surface of applicator cap <NUM> geometrically matches the elevator face <NUM> of elevator <NUM>, which effectively eliminates dead space.

Protective cover <NUM> helps to prevent inadvertent loss of mixed formulation <NUM> by sealing exit holes <NUM>. In this embodiment, cover inner surface <NUM> matches applicator surface <NUM> size-to-size, essentially blocking exit holes <NUM>. Alternatively, protective cover <NUM> can include protrusions or peg-like structures (not shown) that align with and fit into exit holes <NUM> to effect seals.

In this embodiment, protective cover <NUM> is positioned between uses onto applicator cap <NUM> to prevent leakage as well as contamination of applicator surface <NUM>. Protective cover <NUM> may be retained on applicator cap <NUM> by a friction interference fit, as shown here, or by snap-fit lugs or rings commonly used in the propel-repel container art.

<FIG> shows an alternate configuration for a protective cover that employs a bayonet-style attachment. Protective cover <NUM> attaches to applicator cap <NUM> with an insert- and-twist action. Removal is by a reverse twist and pull action. Applicator cap <NUM> includes bayonet lugs <NUM> that protrude so as to catch on bayonet ramps <NUM> of protective cover <NUM> (see <FIG>). This snugs and fixes protective cover <NUM> onto applicator cap <NUM>, axially, when protective cover <NUM> is right-hand rotated onto cap <NUM>. At the same time, bayonet lugs <NUM> ride up detent ramps <NUM>, coming to rest in detent nests <NUM>. This detenting action maintains protective cover <NUM> in position on applicator cap <NUM> until protective cover <NUM> is unscrewed as needed for metering a dose.

An alternative embodiment of a metered dose topical applicator <NUM> is shown in <FIG> wherein the elevator and drive screw are a single component, elevator <NUM>, this embodiment being otherwise similar to that previously described.

<FIG> shows one alternative embodiment of a metered dose topical applicator <NUM> for which the locations of the drive and driven threads of the propel mechanisms are switched. In this case, actuator knob <NUM> is connected to drive screw <NUM>. Elevator <NUM> includes female threads (not shown) that mesh with drive threads <NUM>. Other features as previously disclosed, such as fast purge and indexed metering, can be devised in this embodiment, which has the disadvantage of the drive screw being disposed within reservoir <NUM>. Thus, compounding a formulation directly in the metered dose topical applicator <NUM> must somehow accommodate the presence of drive screw <NUM>.

It is also readily apparent from <FIG> that filling reservoir <NUM> with compounding constituents, either before or after mixing, would be more difficult than with the screw-less reservoir <NUM> of <FIG>. Thus, even if the embodiment shown in those figures is not used as a mixing container, its preparation is simplified over either the embodiment of <FIG> or the prior art.

The location and configurations of drive and driven threads is not limited to the realizations disclosed above. For example, the embodiment shown in <FIG> can position the female driven threads extended downward and entirely beneath elevator face <NUM> such that drive screw <NUM> need not extend into reservoir <NUM>. In other words, the location and configuration of the drive and driven threads are not constrained by any functional performance disclosed above, but are instead chosen by the internal geometry associated with manufacturing and assembly considerations.

<FIG> shows a scheme for labeling and packaging embodiments of a metered dose topical applicator <NUM>. Prescription label <NUM>, which includes appropriate patient and medicament identification, is affixed to the exterior of topical applicator <NUM>, which is then inserted and sealed in an envelope <NUM> that can incorporate instructions for use either therein or thereon.

<FIG> show one configuration of a prefilled metered dose topical applicator. In this embodiment, topical applicator <NUM> includes a barrel <NUM> with barrel threads <NUM>. Sealing cap <NUM> mates via internal threads (not shown) with barrel threads <NUM>, and forms a seal when barrel upper end <NUM> contacts inner seal surface <NUM> of sealing cap <NUM> (<FIG>). Various cooperating geometries are well known in the art for effecting a suitable seal between barrel <NUM> and sealing cap <NUM>.

In practice, topical applicator <NUM> can be filled with topical cream <NUM> during manufacturing in a factory. A sealing cap <NUM> is then applied to seal in the contents during transport and storage.

Topical cream <NUM> may be a neat cream intended only as a carrier into which medicaments will subsequently be compounded. In that case, a compounding pharmacy will first remove sealing cap <NUM>, add one or several medicaments, then mix the contents as herein previously described. Also as previously described, the compounding pharmacy will affix an applicator cap <NUM>, prime, and label topical applicator <NUM> before providing it to the user.

Alternatively, topical cream <NUM> may be a medicament-containing formulation in a ready-to-use condition. In that case, topical applicator <NUM> does not require compounding, and may be provided directly to the user.

Effecting a seal for topical applicator <NUM> after filling is shown in <FIG>. Peelable seal <NUM> is applied to barrel <NUM> after the topical cream <NUM> has been loaded. Peelable seal <NUM> can be, for example, a heat-sealed foil composition well known in the art, and is intended to bond to barrel upper end <NUM>. Prior to compounding or use as described immediately above, peelable seal <NUM> can be removed by grasping peel tab <NUM>, then peeling it away from barrel <NUM>.

<FIG> show an alternate configuration of effecting a seal for containing the prefilled contents of topical applicator <NUM> during storage and transport. Once topical applicator <NUM> has been assembled up to the appropriate point in the factory, it is filled with topical cream. An applicator cap <NUM> is then applied, onto which a peelable seal <NUM> has been, or can be, bonded. In this case, which is well-suited for medicament-containing formulations, peelable seal <NUM> can be removed by the user by grasping and pulling up on peel tab <NUM> to expose exit holes <NUM> in preparation for dosing.

<FIG> and <FIG> illustrate forms of packaging for the topical applicator(s), particularly of the prefilled according to <FIG>.

A protective cover may be provided that attaches to the applicator cap, which can function as described elsewhere herein.

<FIG> and <FIG> describe different methods of preparing a metered dose topical applicator.

<FIG> describe different methods of preparing a metered dose topical applicator that are typically performed at a compounder, such as a pharmacy.

<FIG> illustrates different geographic locations A, B, C, and D where various steps of the methods described herein may be performed. For example, at location A, the topical applicator may be manufactured such as by injection molding the component parts and/or assembling them. The empty topical applicators may be sent directly to a compounder, such as a pharmacy, location C. Here the steps as illustrated in <FIG> may be performed, also see <FIG> where the topical applicator is labeled and packaged for the end user. This will typically take place at the pharmacy. The compounding may be at a different location from where the topical applicator is provided to the end user.

The empty topical applicator may be sent to a location B where a base material is added to the topical applicator. Location B may be a pharmacy supply facility. Alternatively, the topical applicator may be filled with a ready-to-use by the end user formulation. At location B, the topical applicators may be sealed and/or packaged as illustrated in <FIG>.

Claim 1:
A topical applicator (<NUM>) comprising:
a housing (<NUM>) comprising a tubular wall portion with an open first end, the housing further comprising an end wall at a second end partially closing said second end, the end wall having a central aperture;
a dispense cap (<NUM>) having
a plurality of apertures closing the open first end;
a cylindrically shaped knob (<NUM>) positioned at the second end of the housing, the knob having an outer diameter equal to or greater than the diameter of the housing;
an elevator (<NUM>) slidingly and sealingly engaged with an interior surface of the housing, an open interior between the dispense cap and elevator defining a reservoir (<NUM>);
a drive mechanism (<NUM>) comprising a drive nut (<NUM>) and a threaded drive screw (<NUM>) connected intermediate the knob (<NUM>) and elevator (<NUM>), whereby rotating the knob moves the elevator toward the first end of the housing,
characterized in that,
the drive nut (<NUM>) and threaded drive screw (<NUM>) of the applicator are disengageable from each other by an axial separation force applied from exterior of the applicator;
the elevator (<NUM>) is exteriorly accessible through the end portion of the housing whereby the axial separation force may be applied to the elevator to move the elevator toward the first end of the housing without rotation of the knob.