Abstract:
The various embodiments of the present invention relate to a human identical flowable hormone composition dispersed in a cream or gel contained in the novel “Smart” metered dose applicator, which facilitates numerous patient specific dosing options, dose titration, as well as continuous and variable dosing. The composition is designed for transdermal usage for consumers who follow a specified dosage protocol resulting in static and cyclic variations on serum hormone levels over a 28 day cycle stretched over the span of a month. The regimen is modeled after nature, in an attempt to replicate temporal variations in serum progesterone and estradiol hormone levels of premenopausal females with healthy hormone cycles. A dispenser is also disclosed for flowable cream-base medicaments, specifically; a unidirectional rotatable platform attached to a screw that is slipped into a barrel where it is secured in place and it joins the said components that house an elevator.

Description:
PRIORITY PATENT APPLICATIONS 
       [0001]    This is a continuation-in-part patent application drawing priority from U.S. patent application Ser. No. 13/275,282; filed Oct. 17, 2011, and issued as U.S. Pat. No. 8,544,684. This non-provisional continuation-in-part patent application also claims priority to U.S. provisional patent application Ser. No. 61/443,029; filed on Feb. 15, 2011 by the same applicant as the present patent application. This present patent application draws priority from the referenced patent applications. The entire disclosure of the referenced patent applications is considered part of the disclosure of the present application and is hereby incorporated by reference herein in its entirety. 
     
    
     COPYRIGHT NOTICE 
       [0002]    A portion of the disclosure of this patent document contains material that is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark Office patent files or records, but otherwise reserves all copyright rights whatsoever. The following notice applies to the disclosure herein and to the drawings that form a part of this document: Copyright 2009-2013, Ramiro M. Perez; All Rights Reserved. 
       TECHNICAL FIELD 
       [0003]    The various embodiments of the present invention relate to the delivery topical human identical hormone replacement therapy (HIHRT), in particular to selected compositions suitable for transdermal delivery of HIHRT, a novel smart metered dose delivery device recently elucidated that facilitates both, the variable and the continuous dosing of hormones when applied to human skin; and a novel method for self-administering HIHRT through the skin route of women, both in a variable and continuous dosing manner; which attempts to mimic the temporal variations seen in serum human identical progesterone and estradiol hormone levels of healthy premenopausal women over a typical 28 day cycle. In addition, the present protocol maintains a rational dosing therapeutic window amongst specialty providers that could be adjusted to meet unique patient needs. As result, the prescriber has a full repertoire of concentration options of progesterone and estradiol; and an array of dosing combinations between topical human identical estradiol and progesterone, resulting in optimal dose control and positive patient outcomes. A dispenser is also disclosed for flowable cream-base medicaments, specifically a unidirectional rotatable platform attached to a screw that is slipped into a barrel where it is secured in place and it joins the said components that house an elevator. 
       BACKGROUND 
       [0004]    Human Identical hormones have been used since the 1930&#39;s. Throughout the advancements in science, there have been several improvements in medical delivery devices and delivery compositions that employ lipophilic gel or cream bases. Nonetheless, most HIHRT dosing protocols have remained much like those since inception where continuous dosing of HIHRT is predominant amongst medical providers. 
         [0005]    Presently, only a handful of physicians who administer the latest medical treatments to patients attempt to add a cyclic component to their patient&#39;s dosing regimen in order to better maintain their health. Some providers prescribe a static dosing for 6 days out of the week and tell their patients to refrain from taking any HIHRT on day seven. Others prescribe a static daily progesterone dose on the later part of the cycle, (on days 12 or 14 through day 28) and several other variations exist. 
         [0006]    U.S. Pat. No. 7,879,830 exploits the use of syringes, (needle excluded) to be filled with transdermal composition of bioidentical estradiol and progesterone. The user is directed to self-administer a single concentration of estradiol and a single concentration of progesterone and vary the amount of topical composition to be applied following a dosing schedule. Therefore, the user applies the dose by carefully looking at the small demarcations lines on a syringe in order to apply the correct dose. 
         [0007]    Seemingly, U.S. Pat. No. 7,879,830 causes all of its users to conform to a single dosing concentration of bioidentical estradiol, (1 mg 0.1 ml) dispensed in a first (3 cc) syringe (needle excluded), and to a single dosing composition of bioidentical progesterone (25 mg/0.1 ml) dispensed in a second (3 cc) syringe that follows a dosing schedule that is supposed to replicate a “physiologic reproductive hormone cycle in its dose and schedule.” 
         [0008]    In light of the recent advancements in science, which demand a cyclical dosing pattern in order to achieve a better outcome and quality of life, it follows that the greatest challenges prescribers face today are the following: Accurate and patient friendly delivery devices capable of offering dosing flexibility, a dosing protocol that is sound to medical providers; specifically one where the provider is able to select patient specific dosages of progesterone or estradiol in accordance to their body&#39;s needs, and lastly, a protocol that would facilitate patient self-administration and would confer the ability to provide both, static and variable dosing of human identical hormone therapy that overcome the aforementioned deficiencies of the prior art. 
         [0009]    American compounding pharmacists are increasingly dispensing hormone replacement therapy (HRT) cream-base medicines due to raised awareness of its safety profile and benefit in relieving symptoms of hormone imbalance. The challenge to dispense accurate amounts of cream-base medicine continues since delivery device options have been very limited. Not so long ago, a prevalent option for administering cream-base HRT employed the use of ⅛, or ¼ teaspoonfuls, (looking much like an ice-cream sampling spoons) partaking in a common practice called “eye balling.” Syringes are still commonly used today in the delivery of hormone replacement therapy; whereby the pressing of the plunger pushes the cream out of the chamber through the small syringe orifice (needle excluded), and the user is able to get the correct dose by counting number differences or the number of line markings passed by the indicator. 
         [0010]    New metered only transdermal applicators have shown some interest amongst providers and consumers. For example, pumps have been extensively employed where the user depresses a pump that delivers a “somewhat” fixed volumetric amount. (There seems to be a lot of skepticism on the actual accuracy of these devices, especially dosing differences from the first to the second pump). Furthermore, pharmacists and physicians often have to adjust their dosing by taking into account large and inadequate volumetric amounts delivered by these metered-only devices. (i.e. 0.6, 0.7, 0.9 ml per pump). Needless to say, there is extensive variability between pumps. 
         [0011]    U.S. Pat. No. 7,213,994, as disclosed, allows for the delivery of a “predetermined” amount of cream through an opening in the cap. Basically, when the base is rotated 90° (clockwise, an audible and tactile “Click” is supposed to be heard translating to the delivery of a predetermined amount of cream. Furthermore, the patent claims a positive sensory feedback mechanism that confirms a desired amount of cream dispensed. The device is described as producing; in most cases, an audible sound upon a 90-degree clockwise rotation. However, consumers have reported a lack of audible sound or tactile feel on several cases, especially when the rotatable base is left in between clicking segments for prolonged periods of time, which makes it enormously difficult for consumers to apply a desired dose. The problem may be highly attributed to poor design, manufacturing defects, and poor quality assurance. To make matters worse, the said patent only delivers 0.476 g of cream-base medicament of a specific density per 1800 displacement of the base past the barrel, (or per 2-clicks as reported by the company using the Medisca® HRT Cream Base). Thus, falling short from the needed 0.5 gram standard dosing requirement. 
         [0012]    Although both types of metered only transdermal applicators have gained some popularity amongst U.S. compounding pharmacies, (especially if compared to other delivery devices, like syringes, metered screw-on caps, pea-sized spoons, etc.) the greatest challenge faced by these devices, is convincing users, and especially health providers that a “Click” or a “Pump” translates to a specific dose. Therefore, prescribers still refrain from writing in their scripts a dose based on clicks or pumps. Instead, for several decades, providers and patients seem to favor dosages based on a number scale or with some form of graduated line markings. Further, poor mechanical design and 90 degree “click” limitations may be undesirable features to other consumers and providers. In this patent we have solved most the frustration medical prescribers and patients face today when it comes to selecting a useful device for delivering customary doses of transdermal hormone replacement therapies, as well as other uses unknown as of now. The present device offers consumers the delivery of calibrated volumetric amounts of cream-base medicament, a graduation area that allows consumers to visually measure a specified dose, the delivery of smaller, yet consistent volumes if desired, concurrent bi-audible, and bi-tactile features to provide dosing reassurance, and superior flexibility in the dosing of cream-base medicaments without the limitations of “pumps” or “clicks” posed by metered only devices. 
       SUMMARY 
       [0013]    Accordingly, the various embodiments of the present invention are directed to a novel dosing protocol that utilizes a novel delivery system by which an elaborate set of instructions cause a combined continuous and variable topical composition dosing scheme of human identical progesterone and estradiol when self-administered by a user. The protocol aims at simulating the temporal variations as seen in serum progesterone and estradiol hormone levels of premenopausal women with healthy cycles. Accurate and flexible volumetric dosing of said composition for self-administration is made possible through the use of the smart metered dose applicator, the HRTicker® as described herein. The novelty of this dosing protocol is that it facilitates prescribing, patient education, and it increases patient outcomes and quality of life. 
         [0014]    In various embodiments of the present invention described herein, a combined continuous and variable HIHRT protocol is modeled from scientific observations on how temporal variations in serum progesterone and estradiol hormone levels fluctuate in healthy women over a 28 day cycle. The downstream impact of temporal variations in serum hormone concentrations is quite complex, yet highly speculated as a key element in the signaling pathways for how endocrine glands effect remote target organs, and therefore, have a largely impact in the health and wellbeing of women. Furthermore, the latest advancements in science make a strong case for the cyclic delivery of HIHRT in order to achieve optimal health. It follows that a protocol that combines both, static and cyclic dosing of human identical progesterone and estradiol over a 28 day cycle stretched over a Gregorian calendar month in an attempt to replicate the temporal variations in serum hormone concentrations as seen in nature, is likely to improve patient outcomes and quality of life. Additionally, a recently published study that paid particular interest to the differences in myocardial infarctions in patients that received static versus cyclic regimens showed positive outcomes in the group that received the cyclic dosing regimen. 
         [0015]    This novel dosing regimen as described herein empowers prescribers with the option to select various concentrations of human identical estradiol and progesterone according to individual patient needs. Once a hormone concentration is prescribed, then the consumer has the ability to self-administer such concentration topically in a combined continuous and cyclical fashion simulating the temporal variations in serum hormone concentrations as seen in premenopausal women with healthy hormone cycles. All achieved, simply by following the dosing schedule provided with said protocol. 
         [0016]    Perhaps the greatest strengths of the proposed protocol are two-fold. First, it equips medical providers with the ease and flexibility of providing to their patients numerous dosing options (dosing strengths, steps) of estradiol and progesterone that combine static and cyclic dosing regimens at any dosing strength selected for a particular patient. Second, the smart metered dose delivery system described herein (HRTicker® manufactured by BiosRx, Inc.) facilitates self-administration of variable volumetric dosages of human identical estradiol and progesterone in a topical composition to its user, as prescribed. This is vital, since patients can now self-administer complex dosages (static and variable volumetric dosages of composition) by following pre-printed dosing instructions throughout a 28 day cycle stretched over a Gregorian calendar month for practicality. 
         [0017]    Several embodiments are also disclosed, in which a novel device employs a unidirectional rotational mechanism where visual, audible, and tactile elements work together synergistically for the delivery of calibrated volumetric amounts of topical cream-base medicaments of a specified density, or any other flowable material if warranted. The interaction of primary and secondary ticker tabs stemming from the bottom exterior wall of the house and corresponding major, minor, and redundant side ticks stemming from the rotatable platform, which allows for the delivery of specific volumetric amounts of cream-base medicaments, has not been elucidated until now. 
         [0018]    Moreover, the interaction and involvement of selective ticker tabs stemming from the clicking zone of the house and corresponding major, minor, and redundant side ticks stationed on the rotatable platform, which are responsible for creating two different types of audible sounds and tactile sensations to the user depending on the angular displacement of the rotatable element against the house from a predetermined point of reference will be disclosed in detail. 
         [0019]    The term ‘housing element’ or ‘house’, will be used to denote a barrel side ticks as an alternative name to side tabs, and composition as an alternative name to cream-base medicament as disclosed. One example embodiment of the dispensing apparatus includes a unidirectional rotatable platform that engages the head-bolt of a left threaded screw-complex that can be slipped into the inner chamber of the housing element and secured in place by cooperation of a snap-ring and locking tabs located on the bottom wall of the house. Once inside, the screw interacts with an elevator that fits tightly against the wall of said inner chamber. Upon clockwise axial movement of the rotatable platform against the house, audible and tactile sensations can be perceived by the user at every 18 degrees of rotation; however, the type of sound depends if the 18° rotation of the platform is directed to a minor digit tab (minor tick note, soft click) or to a major digit tab (major tick note, louder sound) since different ticker tabs are involved and interact with major, minor, or redundant side ticks depending on the displacement of the rotatable platform against the house from a predetermined point of reference. The elevator rises and pushes upward the flowable contents of such chamber, exiting through an output orifice located at the center of a dispenser, which is secured to the upper end of the house providing a surface to apply the cream or gel directly onto the skin. A removable cap with a plug to retard evaporation of the cream-base medicament is stationed on top of the dispenser. As the platform rotates, the user is able to count the number of equispaced digit tabs on the rotatable platform past the markings on the first end of the house for determining a desired dose. A left threaded rod interacts with an elevator equipped with a top and bottom edge seal useful in preventing a cream smudge trail or any visible cream from being left behind and causes it to rise. A bi-audible mechanism is in place for determining set volumetric amounts dispensed upon an 18° clockwise rotation of the rotatable platform against the house. A 90°, 180 °, 270°, or a 360 degree displacement of the rotatable platform against the house from a predetermined point of reference produces a peculiar audible and tactile sensation on the user, referred here as the first sound. Likewise, displacement other than a 90°, 180 °, 270°, or 360 degrees from a predetermined point of reference, produces a different yet distinct audible and tactile sensation on the user, referred here as the second sound. An 18° rotation of the base platform translates to a 0.05 numerical difference on the exterior wall of the rotatable platform, or one digit tab movement of the rotator past the house. It follows that a 90° rotation translates to a 0.25 numerical difference on the exterior wall of the rotatable platform with respect to the house. The device has been configured to deliver roughly one gram of a specified cream of a specific density (or 1.03 g of water at 25° C.) for every 360° rotation of the rotatable platform against the house. A dispenser pad is available to aid in the application of the cream-base medicament if so desired by the consumer. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0020]    The disclosed embodiments will be further explained with reference to the attached drawings, wherein like structures are referred to by like numerals throughout several views. The drawings displayed may not be to scale, with emphasis instead generally being placed upon the illustration of the principles of the presently disclosed embodiments. 
           [0021]      FIG. 1A  which is a front perspective view of a complete assembled apparatus for dispensing any flowable composition in reference to the various embodiments; 
           [0022]      FIG. 1B  which is a vertical cross sectional view of an assembled dispenser; 
           [0023]      FIG. 1C  which is a magnified horizontal cross-sectional view of the bottom end of the assembled dispensing apparatus with an arrow positioned just below to indicate rotational orientation of the rotatable platform; 
           [0024]      FIGS. 2 ,  3 , and  4 ; which are schematic views of the rotatable platform; 
           [0025]      FIGS. 5A ,  5 B,  6 ,  7 ; which exhibit different schematic views of the house; 
           [0026]      FIG. 8  which is a side view of the screw-complex comprising a head bolt, joined washer, snap ring, and screw; 
           [0027]      FIG. 9  and  FIG. 10  which present 3-dimensional views of the elevator displaying a top and a bottom edge seal, a top outer wall, and a female threaded ring, and a center void; 
           [0028]      FIG. 11  and  FIG. 12 ; which depict two perspective views of an isolated dispenser with the top and bottom views exposed; 
           [0029]      FIG. 13  and  FIG. 14 ; which present two perspective views of the safety cap suspended in mid-air; 
           [0030]      FIGS. 15 through 28  illustrate alternative embodiments of an apparatus for dispensing any flowable composition in reference to the various embodiments; 
           [0031]      FIGS. 29A and 29B  are depictions of the HRTicker® Smart Metered Dose Applicator as described herein, courtesy of BiosRx, Inc., shown in two different colors in  FIG. 29A . Also, a depiction in  FIG. 29B  displays the direction of rotation of the base past the chamber of the applicator. The applicators shown facilitate the delivery of static and cyclical volumetric metered dosages of transdermal human identical progesterone and estradiol hormones. Note: each actuation, (an 18 degree rotation of the base against the chamber) delivers roughly a 1/20th of a gram volumetric dosage of estradiol or progesterone dispersed in a lipid based cream or gel of a specific density; 
           [0032]      FIG. 30  displays a sample scheduling chart for the consumer&#39;s self-administration of human identical progesterone in a dosing manner that is both continuous and variable throughout a women&#39;s 28 day cycle that is stretched over a Gregorian calendar month. The chart also denotes topical self-application of the hormone composition through the use of the HRTicker® smart metered dose applicator described herein; 
           [0033]      FIG. 31  displays a sample scheduling chart for the consumer&#39;s self-administration of human identical estradiol in a dosing manner that is both continuous and variable throughout a women&#39;s 28 day cycle that is stretched over a Gregorian calendar month. The chart also denotes topical self-application of the hormone composition through the use of the HRTicker® smart metered dose applicator; 
           [0034]      FIG. 32A  is a graph displaying progesterone dosing as a function of time (mg/day). Note, the dosing appearing as a continuous dosing on days 1 through 12; and variable dosing on days 13 through 28. The dosing on days 29 through 31 if present on calendar month at any given year is also continuous; 
           [0035]      FIG. 32B  is a graph displaying estradiol dosing as a function of time (mg/day). Note, the dosing appearing as a continuous dosing on days one through 6 and variable dosing on days 7 through 28. For practical purposes, the dosing on days 29 through 31 if present on calendar month at any given year is also continuous; and 
           [0036]      FIG. 33A  and  FIG. 33B  are sample prescription scripts to illustrate how easy a prescription can be written to inform pharmacists and pharmacies that the static and cyclic protocol is being indicated for the patient. Note, the names of the patient and doctor are fictitious and for illustration purposes only. The key words “s&amp;cHRT Protocol” denote, “Static and Cycling Hormone Replacement Therapy Protocol). 
       
    
    
     DETAILED DESCRIPTION 
       [0037]    In various embodiments, a transdermal, visual, bi-audible and bi-tactile to the senses cream applicator with calibrated, equispaced line demarcations, and supplemental numerical legend, each positioned at a predetermined 18 degree angle from one another translating to the delivery of roughly a 1/20 th  milliliter of flowable cream-base medicament of a specific density is described in detail herein. Additionally, a novel dosing protocol is described that utilizes a novel delivery system by which an elaborate set of instructions cause a combined continuous and variable topical composition dosing scheme of human identical progesterone and estradiol when self-administered by a user. 
       Applicator of Example Embodiments 
       [0038]      FIGS. 1-14  depict an embodiment of a dispensing apparatus  5  with regard to this novel system for the delivery of cream, gel, ointment, or any suitable flowable substance of interest. 
         [0039]    This novel applicator  5  comprises the following six vital elements: a rotatable platform  25 , a house  470 , a screw-complex  200  (see  FIG. 8 ), an elevator  325 , a dispenser  500 , and a safety cap  600 . 
         [0040]    All parts can be made of rigid plastic or a similar material, but the preferred material is polypropylene. Prototypes can be designed in ProJet, Stereolithogray (SLA), or Acura  25 . 
         [0041]      FIGS. 1A and 1B  introduces the assembled apparatus  5  as a complete unit ( FIG. 1A ) or as a vertical cross sectional view, ( FIG. 1B ) where the house  470  is located in between the dispenser  500  and the rotatable platform  25 . The elevator  325  rests at the bottom of the inner chamber of the house  470  where the left threaded screw-complex  200 ; which is secured in between the house  470  and the rotatable platform  25  causes it to rise upon clockwise rotation of the rotatable platform  25 . A safety cap  600  with a plug  630  to retard evaporation and prevent contamination of the cream is situated on top of the dispenser  500 ; where the safety cap  600 , which can snap into the dispenser end of the house by cooperation of the semi-annular rib  645  on the inner wall of the safety cap  600  and the safety rim  408  on the outer wall of the dispenser end  401  of the house  470  adjacent to the upper rim  415 . The dispenser  500  gets locked into the dispenser end  401  of the house  470  by interaction of the annular groove  540  on its inner side wall  550  and the peripheral rim  407  on the outer wall of the dispensing end  401  of the house  470 . An outer slim wall  555  fits in between the elevator&#39;s outer side wall  315  and the inner side wall  35  of the house  470 . The elevator  325  and screw shaft  245  inside the house  470  interact only to allow upward movement upon clockwise rotation of the rotatable platform  25 . The house locking tabs  425  override the snap ring  210  landing into the orbit area  240  and locking the screw-complex  200  in place only to allow axial movement. Platform locking tabs  145  override the bolt-head  220  and secure the bolt-neck  235 , thereby locking the rotatable platform  25  in place. The strategic position of the bolt neck  235 ; which, resides in between the joined washer  215  and the bolt head  220  serves to secure the platform locking tabs  145  that stem from the bottom inner wall  105  of the rotatable platform  25  and consequently the rotatable platform  25  as a whole to prevent movement to such segment in any direction. Once the rotatable platform  25  is attached to the screw-complex  200 , the only possible movement, which involves the cooperation of the rotatable platform  25  and the screw-complex  200  behaving as a single unit, is to rotate clockwise around its own axis. 
         [0042]    With the screw-complex  200  set in place interacting with the rotatable platform  25 , house  470 , and elevator  325 , its mechanism can be fully appreciated. The primary ticker tabs  435  interact with minor side ticks  110  on the rotatable platform  25 , and produce a unique and identifiable sound depending on the displacement of the rotatable platform  25  against the house  470 . Upon an 18° displacement, primary ticker tabs  435  can clear the minor side ticks  110  to land into tab rest segments  111  and produce the second sound, or they can clear the major side ticks  112  to land into different tab rest segments  111  to produce the first sound. When the secondary ticker tabs  440  clear the redundant side ticks  115  upon an 18 degree rotation of the rotatable platform  25 , the first sound is also emitted by the apparatus and captured by the senses of the consumer. Therefore, primary ticker tabs interact with major side ticks concurrently when secondary ticker tabs interact with redundant side ticks. Advantageously, there are only four major side ticks  112  strategically positioned to interact with the primary ticker tabs  440  and produce a louder identifiable sound only at key displacement locations; specifically at every 90°, 180°, 270°, and 360° displacement locations from a predetermined reference point; which also corresponds to the alignment of the 0.25, 0.50, 0.75, and 1.0 major digit tabs  70  of the rotatable platform  25  with the fixed major line markings  65  of the house  470 . 
         [0043]    In addition, at these four displacement locations, (90°, 180°, 270°, and 360°) there is sound summation taking place due to the concurrent interaction of primary ticker tabs  435  with major side ticks  112 , as well as secondary ticker tabs  440  interacting redundant side ticks  115 ; ultimately yielding a more pronounced sound and tactile sensation at these predetermined sites. 
         [0044]      FIG. 1C  presents a horizontal cross-section of the lower end of an assembled apparatus emphasizing major  70  and minor  65  digit tabs. There are twenty digit tabs arranged in reverse ascending order along the equispaced digit zone  133 , and each digit tab is separated by an 18° angle from one another. The attachment of the rotatable platform  25  with the housing  470  creates the graduation area  85 ; which is essential in allowing users to determine a specified volumetric dose. A cartoon arrow below the illustration  75 , points to the direction of allowed movement of the unidirectional rotatable platform  25 . 
         [0045]    There are four grip tabs  30  to ease rotation. Further, the lower end of the house  470  provides equispaced extruded line demarcations to create a predetermined point of reference during rotation of the rotatable platform  25 . Fixed major markings  65  and fixed minor markings  50  span along the outer circumference of the lower end of the house  470 . An elevator  325  residing inside the chamber of the house  470  is attached to the screw shaft  245  and causes it to rise upon clockwise rotation of the rotatable platform  25 . 
         [0046]      FIGS. 2-4  are schematic views of the rotatable platform  25 , where the outer side wall  155  of the rotatable platform houses the equispaced digit zone  133  which comprises four raised major digit tabs  70 , and sixteen raised minor digit tabs  65  all arranged in ascending order (by 0.05 intervals) as the platform  25  rotates clockwise against the house  470 . In addition, the platform outer side wall  155  has four side grips  30 ; each situated right below each major digit tab  70  (positioned at 90° degrees from each other along the outer circumference) which span along the equispaced digit zone  133  to facilitate rotation of the platform  25 . The platform lip  120  makes contact with the graduated ring base  495  of the house  470  to create the graduation area  85 , ( FIG. 1A ).  FIG. 4  presents the bottom end of the rotatable platform  25  where side arrows  195  and bottom arrows  190  indicate the direction of movement allowed by the rotatable platform  25 . 
         [0047]      FIG. 2  and  FIG. 4  are schematic views of the rotatable platform  25  where locking tabs  145  extend upward from the center of the bottom inner wall  105 , having six slanted but downward pointing locking tabs  145  which serve to override the bolt head  220  and land onto the bolt neck  235  practically fusing the screw-complex and rotatable platform  25  as one piece. The rotatable platform  25  outer base rim  160  houses sixteen minor side ticks  110  and four major side ticks  112 ; which interact with ticker tabs stemming from the bottom exterior wall  480  of the house  470 . Additionally, four redundant side ticks  115  equispaced from one another stem from the inner base rim  150  of the platform  25  to engage with four secondary ticker tabs  440  also stemming from the outer bottom exterior wall  480  of the house  470 . The inner side wall  100  of the rotatable platform  25  could potentially house major and minor side ticks as well in lieu of the outer base rim  160 . 
         [0048]      FIG. 4  presents another schematic view the rotatable platform  25  where the bottom exterior wall  185  of the rotatable platform  25  is clearly exhibited. The locking tabs  145  point inward towards the bottom of the hexagon void  175 . There is one locking tab  145  stemming from each upper corner of the hexagon side wall  180 ,  181 ,  182 , where the two walls join. Further, bottom indication arrows  190 , and side indication arrows  195  show the direction of allowed movement of the rotatable platform  25 . 
         [0049]    The house  470 , which is basically a barrel, is introduced in  FIG. 5A ,  FIG. 5B ,  FIG. 6  and  FIG. 7 , having three major sections. A dispenser end  401 , a body  402 , and a platform end  403  comprising a graduation ring  430  and a clicking zone  404 . The body  402  of the house  470  consists primarily of an inner side wall  35 , and the outer side wall  40 ; which, can accommodate a label with consumer instructions. At the dispenser end  401 , there is a dispenser opening  405  used to load the cream-base medicament into the chamber of the house  470 . There are two dispenser notches  475   a ,  475   b  at opposite ends of the circular upper edge  410 ; which guide the insertion guides  530  of the dispenser  500  to properly slip in upon pressing against the house  470 . A peripheral rim  407  on the house outer side wall  40  engages with its complementary annular groove  540  on the inner side wall  550  of the dispenser  500  locking it upon pressing against the house  470 . 
         [0050]    An extruded upper rim  415  with reinforcement ribs  416  just beneath it is situated just below the circular upper edge  410  which assists in locking the dispenser  500  upon pressing against it. The inner side wall  35  of the house  470  is directly in contact with the composition and it is perpendicular to the bottom inner wall  479 ; which, on its center has a void with four upward projecting locking tabs  425  for accepting and locking the screw-complex  200  in place with the house  470  only to allow rotation along its own axis. The chamber upper edge  484  concludes the upper end of the chamber; which has a semi-square shape in order to maximize volume, but it is connected to the circular upper wall  406  by a wall to wall connector  485 , that terminates at the top with the circular upper edge  410 . 
         [0051]    The platform end  403  of the house  470  has a raised graduation ring  430 , with twenty demarcation line markings, referred here as fixed major and minor line markings ( 65 ;  50 ); respectively. There are four fixed major line markings  65 , separated at 90° from each other along the outer circumference of the of platform end  403  of the house  470  and sixteen fixed minor line markings  50 , all forming the graduation ring  430 . The primary ticker tabs  435  stemming from the platform end  403  of the house interact with minor side ticks  110  stemming from the outer base rim  160  of the rotatable platform  25  producing a unique but soft second sound at every 18° of rotation depending on the angular displacement from a predetermined point of reference. In addition, the primary ticker tabs  435  also interact with major side ticks  112  stemming from the outer base rim  160  of the rotatable platform  25  to produce a louder first sound upon clearance of the primary ticker tabs  435 . The secondary ticker tabs  440  interact with the redundant side ticks  115  of the rotatable platform  25  to produce the louder first sound upon completion of an 18° movement by the platform to any major digit tab  70  position, (or a 90° predetermined angular displacement from a fixed point of reference) as well as a specific vibration that corresponds to the tactile component that users can sense. Furthermore, an even louder sound and greater tactile sensation is achieved by summation of ticker tabs to side tick interactions; specifically, primary and secondary ticker tabs interacting with major and redundant side ticks, simultaneously, where the landing of all ticker tabs take place upon completion of an 18° displacement into the major digit tabs  70 . A screw orifice  450 , accepts the screw-complex  200  and the locking tabs  425  override the snap ring  210  landing into the orbit area  240  of the screw-complex  200  where the screw-complex  200  is practically locked to the house  470 . 
         [0052]      FIG. 8  illustrates the bolt head  220 , joined washer  215 , snap ring  210 , and a screw  245 . Once combined, all these components form the screw-complex  200 . The pitch  250  is the distance between threads; which, causes a predetermined but specific elevation on the elevator; ultimately having a role on dosing. The screw end  201  of the screw-complex  200  continues downward along the screw  245  until the threading stops at a snap ring  210 ; which, upon passing, it secures the screw-complex  200  to the house  470  cooperating with four upward slanted locking tabs  425  stemming from the bottom inner wall  479  of the house  470  and a joined washer  215  that serves as a securing mechanism. The bolt head  220  has six equal head side walls  230 . The bolt neck  235  is the area between the bolt head  220  and joined washer  215 ; which serves to secure the rotatable platform  25 . 
         [0053]      FIG. 9  is a schematic view of the elevator  325 . The elevator pushes the cream-base medicament, which resides in a closed chamber upwards, to exit through an outlet  505  upon movement of the rotatable platform  25 . The top outer wall  305  is dome shaped with a concave outer side wall  315  where the top edge seal  310  and bottom edge seal  320  are at opposite ends; which, also serves to prevent cream form smudging or being left behind. On the center of the elevator  325 , there is a ring void  300  that interacts with the treaded area of the screw  245 . The bottom view of the elevator  325  is presented on  FIG. 10  where the female threaded ring  330  appears around the center of the elevator  325 , as well as the intrinsic wall  340  where it stems from. There are two assembly stoppers  335 ,  336  to prevent damage to the elevator by the assembly tooling. 
         [0054]      FIG. 11  is a schematic view of the dispenser  500  where the dispensing pad  501  serves as a dispensing element. The outlet  505  allows the cream-base medicament to be expelled and perhaps temporarily reside there until application. The smooth upper edge  510  connects the outer side wall  515  and dispensing pad  501  together.  FIG. 12  is a schematic view of the dispenser  500 , where the bottom side of the dispenser is exposed, causing the following to appear; the top inner wall  520 , the inner side wall  550 , and a dispenser bottom edge  525 . An additional wall exists to seal the cream inside the chamber and prevent dispersion. It consists of an inner slim wall  545 , an outer slim wall  555 , and the slim edge  535 . There are two insertion guides  530  on the inner side wall  550  at opposite positions along the circumference to fit into the dispenser notch  475   a ,  475   b  allowing the dispenser to slip onto the dispenser end  401  of the house  470 . The dispenser  500  snaps tightly into the house  470  and cannot be detached by cooperation of the annular groove  540  and the peripheral rim  407  of the house  470 . 
         [0055]      FIGS. 13 and 14  are schematic views of the safety cap  600  exhibiting the top outer wall  605 , and smooth upper edge  610 , an outer side surface  615 , a lower edge  635 , an inner side wall  640 , an inner top wall  620 , a semi-annular rib  645 , reinforcement ribs  646 , and a plug  630 . 
         [0056]    Pre-Assembly: This involves the collaboration four components; the screw-complex  200 , house  470 , elevator  325  and rotatable platform  25 . The screw end  201  and the screw-complex  200  get inserted to the house  470  past the house locking tabs  425 . Once the locking tabs  425  override the snap ring  210 , the screw-complex  200  gets trapped in the house  470  in parallel with the chamber&#39;s inner side wall and it&#39;s only able to rotate axially. Tooling facilitates assembly of the elevator  325  where counterclockwise rotation of the screw-complex  200  allows the elevator  325  to get screwed into the bottom end of the house  470 . The hexagonal shape of the bolt head  220  allows it to be attached to an electrical female hexagonal-socket and yield assembly of the elevator  325  into the bottom end of the house  470  efficiently. Next, the rotatable platform  25  is slipped into the bottom end of the house  470  where the locking tabs  145  overrides the bolt head  220  to land into the bolt neck  235  where the platform locking tabs  145  secure the rotatable platform  25  into the other said components ( 25 ,  470 ,  200 ,  325 ) in a tight fit, practically fusing the rotatable platform  25  to the house-screw-complex-elevator components. The preassembled unit, along with the dispenser  500 , and security cap  600 , (assembly add-ons) can be shipped as a single unit or in large quantities. 
         [0057]    Assembly: Compounding pharmacists or other dispensing personnel can place a desired quantity of the flowable cream-base medicament inside the chamber of the housing  470  through the dispenser opening  405 . The dispenser  500  gets positioned to fit into the housing  470  through insertion guides  530  that fit into the dispenser notch  475   a ,  475   b . Upon pressing, the annular groove  540  fastens into the peripheral rim  407  of the house  470 . Once locked, the dispenser cannot be removed by the average consumer unless a skilled provider or technician, using a pointy tool can carefully pull the dispenser&#39;s bottom edge  525  and displace the dispenser  500  outwards. Once in place, the applicator gets primed (air removed) to a desired setting by rotating the rotatable platform clockwise; as allowed. We recommend technicians and dispensers to partially prime the unit to prevent spilling; especially if transporting to different altitudes as pressure changes may force the cream-base medicament out of the device. The security cap  600  can be inserted to prevent medicament contamination, spill, and retard medicament evaporation by sealing the outlet  505 . The security cap  600  can also be fastened to a tight fit if one applies additional force by cooperation of the semi-annular rib  645  and safety rim  408 . A thumb tab  611  is placed near the lower edge  635  and lower outer side wall  615  of the safety cap  600  to ease removal. 
       Audible and Tactile Mechanism 
       [0058]    Minor Tick Note: This is the sound and tactile sensation caused by the interaction of primary ticker tabs  435  stemming from the bottom exterior wall  480  of the house  470  with minor side ticks  110  stemming from the outer base rim  160  of the rotatable platform  25  due to an 18° displacement of the rotatable platform  25  against the house  470  to any predetermined minor digit tab (other than digit tabs 0.25, 0.50, 0.75, and 1.0). A soft and distinct sound and tactile sensation is captured by the user upon clockwise rotation of the rotatable platform  25  against the house  470  of the apparatus at any of these predetermined angular displacements allowed. 
         [0059]    Major tick Note: This is the sound and tactile sensation caused by interaction of primary ticker tabs  435  and major side ticks  112  plus the concurrent interaction of secondary ticker tabs  440  stemming from the bottom exterior wall  480  of the house  470  with redundant side ticks  115  stemming from the inner base rim  150  of the rotatable platform  25  due to an 18° displacement of the rotatable platform  25  with respect the house  470  to the following predetermined major digit tabs, 0.25, 0.50, 0.75, and 1.0. This summation, and thus amplification of sound and tactile sensations makes for a bi-audible and bi-tactile apparatus. 
         [0060]    Refill Reminder Indicator: As presented on  FIG. 5A , a small raised horizontal bar  472  near the upper rim  415  serves to indicate to the consumer their cream-base medicament may be running low. Further, the word, “refill” positioned right beneath the upper rim is shown embossed  471  to also remind consumers their medicament may be running-out. A second raised horizontal line  473  sits just about the middle part of the house  470  to indicate pharmacy technicians or other dispensing personnel a rough estimation of a half-filled applicator in cases where the prescribed amount is half the usual amount prescribed, given that one full container may be the norm. There are two additional horizontal lines  476 ,  477  to also help in indicating levels of a 75% or a 100% composition-filled applicator; respectively. A vertical bar  474 , also shown in  FIG. 5A , serves as a guide to properly position an indication label on the face of the outer side wall  40  of the house  470 . 
       Variations 
       [0061]    A variation of the current design is seen in on  FIGS. 15 through 28  where the cream-base medicament is stored in an enclosed cylindrical shaped chamber. In Addition, the major yielding tabs  2270 , and minor yielding tabs  2260  emit a sound at every 18° rotation of the rotatable platform  2000  past the house member  2100 . The main difference is that this device produces an almost identical sound and tactile sensation at every 18° rotation of the rotatable platform  2000  past the house member  2100 . In addition, extruded grapheme letters  2210 , (A,A, B,B, C,C, and D,D) and major line markings  2220  are located in the graduation ring  2230  of the platform end  2280  of the house  2100 . The rotatable platform  2000  has four major slanted grooves  1920  and sixteen minor slanted grooves  1900  on the inner wall  1910  of the rotatable platform  2000  that engage with four major teeth-like projections  2250  and sixteen minor teeth-like projections  2240  stemming from four major yielding tabs  2270  and sixteen minor yielding tabs  2260  that originate from the bottom exterior wall  2400  of the house  2100 ; as seen on  FIGS. 19-24 . The Dispenser  2700  seen on  FIGS. 27-28  has a slightly different inner slim wall  2800  to fit into said elliptical chamber where the composition is stored. The elevator  2500  with an enhanced mid-rim seal  2510  is seen on  FIGS. 25-26  with its cylindrical shape configured to fit on the said house chamber. Each 18° rotation of the rotatable platform  2000  against the house  2100  is configured to deliver a 1/20 th  milliliter of flowable composition. A bi-tactile and bi-audible mechanism is also produced with this design. A first sound corresponding to digit tabs 0.25, 0.50, 0.75, and 1.0 is configured by increasing the depth of fall of major teeth-like projections  2250  into major slanted grooves  1920 . A second sound at positions other than 0.25, 0.50, 0.75, and 1.0 is produced where the major teeth-like projections  2250  and minor teeth like projections  2240  land into minor slanted grooves  1900  where depth of fall of teeth-like projections into slanted grooves is rather shallow. 
       Protocol of Example Embodiments 
       [0062]    Referring to  FIGS. 29A through 33B  of the present disclosure, the various embodiments of the present invention are shown generally at  3100  in  FIG. 29A  displaying two complete units of the smart metered dose applicator, (each one in different colors) the HRTicker® Equipped with a rotatable base  3110  to empower the user in self-administering an indicated volumetric dose, a chamber  3115  to house said flowable composition which contains human identical progesterone or estradiol. The elevator  3120  and rod  3125 , shown in  FIG. 29B , working in conjunction as the base  3110  is turned clockwise against the chamber  3115  to move the composition upwards, which then exits through and outlet and the medication collects in the dispenser cap. A safety cap  3105  acts to retard evaporation. The down-pointing arrows  3130  at the bottom of the chamber  3115  aid in lining the major number tabs  3135  or the minor number tabs  3145  with the chamber  3115  to the correct position as desired by the user. Each actuation, an 18° turn of the base  3110  against the chamber  3115 , delivers roughly 1/20th of a gram of flowable composition of a given density. The user is therefore able to apply the correct dose indicated by a protocol that calls for a continuous, variable, or both, a combined continuous-and-variable dosing regimen. 
         [0063]      FIG. 30  exhibits a series of steps from one to ten  3150  which represent human identical progesterone concentrations  3155  ranging from 20 mg/GM to 200/GM mg. At the middle of the chart, a series of actuations are displayed  3160  where the dosing is time dependent, and the dosage spans over a 28 day cycle that is stretched over a calendar&#39;s month  3160  for any particular year. 
         [0064]    With respect to progesterone dosing, continuous dosing will be defined as a volumetric dosage that is self-administered by a user for more than one day  3170 ,  3175 ,  3180 ,  3185 . In technicality, days 29 through 31 could be regarded as continuous or variable based on the number of days that exist within the month for a given Gregorian calendar year. For practical purposes, we will regard days 29 through 31 as continuous dosing. 
         [0065]    The letter or logo, “P”  3190  is inserted in the chart to assist the user to properly identify the correct dosing schedule for progesterone and minimize dosing errors. Color codes and labeling markings on the smart metered dose applicator will further enhance patient safety and minimize dosing and drug selection errors. 
         [0066]      FIG. 31  presents a series of steps from one to ten  3200  which represent human identical estradiol concentrations  3205  ranging from 0.25 mg/GM to 8.0 mg/GM. The center of the chart  3210  shows a series of different actuations  3210 , which instruct the user how much volumetric composition to apply for any given day in a 28 day cycle stretched over the span of a calendar month  3210 . Days 12, 13, and 14 (items  215  in  FIG. 31 ) were randomly selected to illustrate the principle of how self-administration of the composition is time dependent (time is expressed as days) and variable on those days. The number of actuations is applied twice daily as instructed by the provider. Continuous dosing of human identical estradiol is defined as a volumetric dosage that is self-administered by a user for more than one day  3230 ,  3235 ,  3240 ,  3245 ,  3250 , and  3255 . For practical purposes, days 29-31 will be regarded as continuous dosing. The “E2” logo  3255  is positioned within the chart to assist the user in identifying the correct dosing schedule and minimize dosing errors. Color codes and labeling markings on the smart metered dose applicator will further enhance patient safety and minimize dosing and drug selection errors. 
         [0067]      FIG. 32A  depicts a graph based on human identical progesterone dosing as a function of time (mg/day). The dosing is self-administered by a user following a specific protocol that results in a combined continuous and variable dosing over the span of a 28 day cycle stretch to a Gregorian calendar month. Days 1 to 12 (item  300  shown in  FIG. 32A ) present a static or continuous dosing; whereas days 13 through 28 generally represent a variable dosing regimen by which, the two parts combined attempt to mimic the rhythmic cycle as seen in healthy premenopausal women. Depending on the number of days in a calendar year, days 29 through 31 ( 3310 ) could be regarded as a static or variable dosing regimen. In the interest of practicality, we will denote this interval as a continuous dosing regimen. Day one will be regarded as the first day of a Gregorian calendar month. 
         [0068]      FIG. 32B  depicts a graph based on human identical estradiol dosing as a function of time (mg/day). The volumetric dosage is self-administered by the consumer following a novel protocol where the end result is a combined continuous  3315  and variable  3320  dosing regimen over a the span of a 28 day cycle stretched to a Gregorian calendar month. Days 1 through 6 depict a static dosing regimen  3315 ; whereas days 7 through 28 ( 3320 ) generally depict a variable dosing regimen. Days 29 through 31 ( 3325 ) will be regarded as a continuous dosing regimen for practicality purposes. 
         [0069]      FIG. 33A  illustrates how easy prescribing can be accomplished taking into account that the dosing regimen is quite complex over the span of a month. Nonetheless, since the user can now take advantage of using the smart metered dose applicator (HRTicker®) described herein, dosing is made easy. In this exhibit, the prescriber has written for human identical progesterone cream at a STEP 5 (100 mg/GM) dose; and instructed the pharmacy to dispense the prescription with the schedule required by the protocol described herein. 
         [0070]    Likewise in  FIG. 33B , the prescriber has chosen a STEP 4 (1.5 mg/GM) of estradiol to be dispensed by the pharmacy following the same combined continuous and variable dosing protocol described herein and employing the use of the HRTicker® also described herein. 
         [0071]    The Abstract of the Disclosure is provided to comply with 37 C.F.R. §1.72(b), requiring an abstract that will allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, it can be seen that various features are grouped together in a single embodiment for the purpose of streamlining the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the claimed embodiments require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed embodiment. Thus the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separate embodiment.