A vaginal system containing a core, and methods of manufacture and use thereof

Abstract

A vaginal system for a female, including an outer ring layer having a first silicone polymer and a core having a second silicone polymer and a progestin. When the vaginal system is positioned in a vagina of the female, an amount of the progestin released per day from the vaginal system is from about 10 μg to about 150 μg during a steady state release period. The vaginal system has from about 10 mg to about 250 mg of the progestin. The vaginal system is configured to release the progestin in the vagina for up to about 365 days or up to about 24 months.

Description

A VAGINAL SYSTEM CONTAINING A CORE, AND METHODS OF MANUFACTURE AND USE THEREOFCROSS REFERENCE TO RELATED APPLICATION

[0001] The present disclosure claims the benefit of U.S. Provisional Application No. 63 / 645,194, filed May 10, 2024, the entirety of which is incorporated by reference herein.FIELD OF THE INVENTION

[0002] The present disclosure is related to a vaginal system for a female in need thereof. In particular, the present disclosure is related to a vaginal system comprising an encapsulation material surrounding a drug loaded core and allowing the steady release of a progestin, and a method of contraception using the vaginal system.BACKGROUND OF THE INVENTION

[0003] Oral contraceptives are widely known and used by many females. However, the need to remember a daily pill can reduce compliance, risking effectiveness.

[0004] An alternative way to deliver contraceptives is via a vaginal device. One form of such a vaginal device is a vaginal ring that can be inserted into the vagina.

[0005] While vaginal devices, such as vaginal rings, are useful for certain applications, they have a number of perceived disadvantages, such as costs associated with the need for multiple devices due to short term of use.

[0006] Yet another alternative way to deliver contraceptives is via a subdermal implant. Such subdermal implants can provide a long-term contraceptive, with such devices subcutaneously inserted for up to about 3 years. However, these devices are not only invasive, but they also may not be simple to remove if the patient no longer desires the contraceptive effect of the implant.

[0007] Yet another alternative way to deliver contraceptives is via an intrauterine device (IUD). While IUDs provides a long-term contraceptive, with such devices inserted for up to about 5 or 10 years, IUDs can slip out of place and need to be removed. Also, copper- releasing IUDs can cause cramps, longer and heavier menstrual periods, and spotting between periods. Progestin-releasing IUDs can cause irregular bleeding and spotting during the first few months. Also, IUDs may increase the risk for ectopic pregnancy. Again, thesedevices are not only invasive, but they also may not be simple to remove if the patient no longer desires the contraceptive effect of the device. As with subdermal implants, implantation and removal must be done by a medical professional.SUMMARY

[0008] A vaginal system for a female, including an outer ring layer having a first silicone polymer and a core having a second silicone polymer and a progestin. When the vaginal system is positioned in a vagina of the female, an amount of the progestin released per day from the vaginal system is from about 10 pg to about 150 pg during a steady state release period. The vaginal system comprises from about 10 mg to about 250 mg of the progestin. The vaginal system is configured to release the progestin in the vagina for up to about 365 days or up to about 24 months. The progestin may be etonogestrel (ETO).BRIEF DESCRIPTION OF THE DRAWINGS

[0009] With reference to the appended drawings, below follow some embodiments, aspects, and / or information of the disclosure cited as examples.

[0010] Figure 1 depicts a top view of a vaginal system, according to an embodiment of the disclosure.

[0011] Figure 2 depicts a cross-sectional view of a vaginal system, according to an embodiment of the disclosure.

[0012] Figure 2 depicts a top view of a core ring and various positions for cutting the core ring at different lengths, according to an embodiment of the disclosure.

[0013] Figure 3 depicts a graph showing a mean release of etonogestrel relative to time for various core lengths and ETO loads, according to an embodiment of the disclosure.

[0014] Figure 4A depicts a graph showing a mean release of etonogestrel relative to time for cores at 15% w / w ETO loading and having various lengths, according to an embodiment of the disclosure. Figure 4B depicts a graph showing a mean release of etonogestrel relative to time for cores at 20% w / w ETO loading and having various lengths, according to an embodiment of the disclosure. Figure 4C depicts a graph showing a mean release of etonogestrel relative to time for cores at 20% w / w at various lengths and 45% w / w ETO loading at 35 mm, according to an embodiment of the disclosure.

[0015] Figure 5A depicts a graph showing a mean release of etonogestrel relative to time for cores of length 35 mm and having various ETO loadings, according to an embodimentof the disclosure. Figure 5B depicts a graph showing a mean release of etonogestrel relative to time for cores of length 50 mm and having various ETO loadings, according to an embodiment of the disclosure. Figure 5C depicts a graph showing a mean release of etonogestrel relative to time for cores of length 35 mm and having various ETO loadings for two different rings, according to an embodiment of the disclosure.

[0016] Figure 6A depicts a graph showing a mean release of etonogestrel over bi-monthly increments, according to an embodiment of the disclosure. Figure 6B depicts a graph showing a mean release of etonogestrel over monthly increments, according to an embodiment of the disclosure.

[0017] Figure 7A depicts a bar graph showing a mean release of etonogestrel from day 2 of use to a last-measured day, according to an embodiment of the disclosure. Figure 7B depicts a bar graph showing a mean release of etonogestrel from day 2 of use to day 91 of use, according to an embodiment of the disclosure. Figure 7C depicts a bar graph showing a mean release of etonogestrel from day 2 of use to day 180 of use, according to an embodiment of the disclosure. Figure 7D depicts a bar graph showing a mean release of etonogestrel from day 2 of use to day 364 of use, according to an embodiment of the disclosure.

[0018] Figure 8A depicts a graph showing etonogestrel initial burst release following storage at accelerated stability conditions (40°C / 75% Relative Humidity [RH]), according to an embodiment of the disclosure. Figure 8B depicts a graph showing etonogestrel initial burst release following storage at accelerated stability conditions (40°C / 75%RH), for 50 mm cores, according to an embodiment of the disclosure. Figure 8C depicts a graph showing etonogestrel initial burst release following storage at accelerated stability conditions (40°C / 75%RH), for 35 mm cores, according to an embodiment of the disclosure.

[0019] Figure 9 depicts a graph comparing shelf-life of vaginal systems, according to an embodiment of the disclosure.

[0020] Figure 10 depicts a graph showing shelf-life of vaginal systems, according to an embodiment of the disclosure.

[0021] Figure 11 depicts a graph showing core weight relative to number of cores, according to an embodiment of the disclosure.

[0022] Figure 12 depicts a graph showing core weight relative to number of cores, according to an embodiment of the disclosure.

[0023] Figure 13 depicts a graph showing full ring weight relative to number of cores, according to an embodiment of the disclosure.

[0024] Figure 14 depicts a graph showing cumulative release of etonogestrel over days passed, according to an embodiment of the disclosure.

[0025] Figure 15 depicts a graph showing cumulative release of etonogestrel over days passed, according to an embodiment of the disclosure.

[0026] Figure 16 depicts a graph showing cumulative release of etonogestrel over days passed, according to an embodiment of the disclosure.

[0027] Figure 17 depicts a graph showing cumulative release of etonogestrel and percent of drug remaining over days passed, according to an embodiment of the disclosure.

[0028] Figure 18 depicts a graph showing cumulative release of etonogestrel and percent of drug remaining over days passed, according to an embodiment of the disclosure.

[0029] Figure 19 depicts a graph showing cumulative release of etonogestrel and percent of drug remaining over days passed, according to an embodiment of the disclosure.

[0030] Figure 20 depicts a graph showing cumulative release of the drug over days passed, according to an embodiment of the disclosure.

[0031] Figure 21 depicts a process for preparing the vaginal system, according to an embodiment of the disclosure.

[0032] Figure 22 depicts placement of the vaginal system in the upper third portion of the vagina of a female in need thereof, according to an embodiment of the disclosure.

[0033] Figure 23 depicts a high-level overview of a process for preparing the vaginal system, according to an embodiment of the disclosure.

[0034] The above figures are merely exemplary of embodiments found in the present disclosure. The above figures are in no way to operate in a manner that limits embodiments of the present disclosure and should be used as a supplement for understanding the embodiments discussed in the detailed description below.DETAILED DESCRIPTION

[0035] Contraceptive intravaginal delivery devices have been conventionally utilized to allow females to avoid the need for a daily administration of oral contraceptives. While these devices (e.g., NuvaRing® or Annovera®, both of which including a combination of a progestin and an estrogen) need not be inserted and removed on a daily basis, the typical instructions are to keep them in place for about three weeks, following which they are to be removed, and in many cases discarded, and a new device is to be inserted after a withdrawal period. Such use has its own set of disadvantages. When a device is first inserted, an initialhormone burst is generated, which may cause unwanted side effects, such as bloating, mood changes, fatigue, and headaches. Also, there is a considerable cost associated with having to purchase a new device for every month.

[0036] As an alternative to conventional contraceptive intravaginal delivery devices, subdermal implants and IUDs can be inserted into a female for a longer period of time (e.g., up to about 3 years, 5 years, or 10 years) and, thus, deliver a contraceptive over such a long period of time. Like intravaginal delivery devices, subdermal implants and IUDs avoid the need for daily administration of oral contraceptives. Moreover, some subdermal implants (e.g., Nexplanon®) may contain only a progestin, which is effective on its own to prevent pregnancy without the addition of estrogen. However, subdermal implants and IUDs have disadvantages as well. For instance, application of the subdermal implants is a medical procedure, because these implants must be inserted by a medical professional via a needle that punctures the skin. Application of the IUDs is also a medical procedure, because these devices must be inserted into the uterus by a medical professional. In addition, such implants and IUDs may be difficult to remove if the female decides she would like to become pregnant, or for other reasons including a diagnosis of certain diseases, such as cancer, especially breast cancer or ovarian cancer. In fact, removal of the subdermal implant and the IUD is also a medical procedure, which can be further complicated if the medical professional who inserted the device did so incorrectly. Another purpose for using a vaginal system is hormone replacement therapy, for providing medication containing hormones to aid the female when she is experiencing medical conditions such as menopause. Hormone replacement therapy typically involves an estrogen-containing medication for females in need of estrogen replacement. Hormone replacement therapy also often includes a progestin to counteract the estrogen to prevent further medical complications. Embodiments herein may allow for the use of a vaginal system for hormone replacement therapy.

[0037] The present disclosure provides a vaginal system that makes it possible to provide effective contraception for an extended period of time afforded by subdermal implants or IUDs, while still giving the female control without the need for medical professional to insert or remove the device if it is desired to stop the contraceptive. In addition, because the vaginal system remains in place for an extended period of time, a constant lower level of localized hormones may be delivered, which can reduce the unwanted side effects of more conventional contraceptives, for example, due to estrogen exposure, such as the reduced likelihood of irregular bleeding or weight gain, or in the case of oral regimens, the need toremember to have to take a daily pill. The extended period of insertion also results in fewer menstrual periods, which can help prevent migraines that occur around the time of a menstrual period, as well as to reduce pain caused by endometriosis. It is also possible to provide effective hormone replacement therapy with the vaginal system and methods disclosed herein.

[0038] In addition, the methods disclosed herein allow the same vaginal system to be used for at least 12 continuous months (e.g., about one year) or for at least 24 continuous moths (.e., about two years). Therefore, in accordance with the embodiments disclosed herein, it is possible not only to reduce the total number of menstrual periods per year and the above- mentioned associated physical disadvantages, but it is also possible to reduce the number of intravaginal drug delivery systems that would need to be purchased to obtain such contraceptive benefits.

[0039] Embodiments of this disclosure provide a vaginal system for a female, including an outer ring layer having a first silicone polymer and a core having a second silicone polymer and a progestin. When the vaginal system is positioned in a vagina of the female, an amount of the progestin released per day from the vaginal system is from about 10 pg to about 150 pg during a steady state release period. The vaginal system comprises from about 10 mg to about 250 mg of the progestin. The vaginal system is configured to release the progestin in the vagina for up to about 365 days or up to about 24 months. Preferably, the progestin is etonogestrel (ETO).

[0040] In some embodiments, the vaginal system is configured to release the progestin in the vagina for up to about 365 days.

[0041] In some embodiments, when the vaginal system is positioned in the vagina of the female, the amount of progestin released per day from the vaginal system is from about 30 pg to about 50 pg during a steady state release period.

[0042] In some embodiments, the vaginal system is positioned in the vagina of a female, the amount of progestin in the vaginal system is from about 40 mg to about 80 mg.

[0043] In some embodiments, the vaginal system has a core diameter from about 0.5 mm to about 4.5 mm.

[0044] In some embodiments, the vaginal system has a cross-sectional diameter from about 5 mm to about 20 mm.

[0045] In some embodiments, the progestin is etonogestrel.

[0046] In some embodiments, when the vaginal system is positioned in the vagina of a female, the amount of progestin released per day from the vaginal system is from about 30ig to about 50 pig during a steady state release period, the amount of progestin in the vaginal system is from about 40 mg to about 80 mg, the vaginal system is configured to release the progestin in the vagina for up to about 365 days, and the progestin is etonogestrel.

[0047] In some embodiments, the progestin is in an amount from about 5% w / w to about 50% w / w of the core.

[0048] In some embodiments, amount of the progestin in the vaginal system is from about 0.1% w / w to about 1.0% w / w of the vaginal system.

[0049] In some embodiments, the drug loaded core has a length of from about 20 mm to about 144 mm. In some embodiments, the drug loaded core has a length of from about 25 mm to about 70 mm.

[0050] In some embodiments, the steady state release period immediately follows a transition phase of from about 7 days to about 28 days, wherein the transition phase immediately follows an initial release period of from about 0 days to about 7 days, and wherein the steady state release period lasts up to about 24 months or up to about 365 days after the vaginal system is positioned in the vagina. In some embodiments, the steady state release period lasts up to about 18 months after the vaginal system is positioned in the vagina. In some embodiments, the steady state release period lasts up to about 365 days after the vaginal system is positioned in the vagina.

[0051] In some embodiments, an initial burst release of the vaginal system during the initial release period is equal to or less than 360 pg / day.

[0052] In some embodiments, the vaginal system is configured so that a release of the progestin during the steady state release period results in blood levels of the female of equal to or greater than about 140 pg / mL.

[0053] In some embodiments, the vaginal system is configured so that a release of the progestin during the steady state release period results in blood levels of the female of equal to or greater than about 90 pg / mL. In some embodiments, the vaginal system is configured to be implantable into a vagina of the female by the female. In some embodiments, the vaginal system is configured to be removed from the vagina by the female.

[0054] In some embodiments, the vaginal system is configured to be positioned in an upper third portion of a vagina of the female.

[0055] In some embodiments, the vaginal system does not comprise any estrogen.

[0056] In some embodiments, the vaginal system has an outer diameter of from about 40 mm to about 80 mm.

[0057] In some embodiments, the vaginal system comprises multiple drug loaded cores that are substantially uniform in weight. In other embodiments, the vaginal system comprises multiple drug loaded cores that are not substantially uniform in weight.

[0058] In some embodiments, the outer ring layer is not coated in the exterior.

[0059] Embodiments of this disclosure also provide a method of contraception for a female in need thereof, comprising positioning a vaginal system in an upper third portion of a vagina of the female; and maintaining the vaginal system in situ of the subject for up to about 365 days or up to about 24 months.

[0060] Embodiments of this disclosure also provide a method of hormone replacement therapy for a female in need thereof, comprising positioning a vaginal system in an upper third portion of a vagina of the female; and maintaining the vaginal system in situ of the subject for up to about 365 days or up to about 24 months.

[0061] In some embodiments, the method further comprises inserting the vaginal system into a vagina of the female by the female and removing the vaginal system from the vagina of the female by the female.

[0062] In some embodiments, the vaginal system releases a steady amount of the progestin during a steady state release period, which lasts up to about 24 months after the vaginal system is positioned in the vagina.

[0063] As used herein, the singular forms “a,” “an,” and “the” include the plural reference unless the context clearly dictates otherwise.

[0064] As used herein, a “female in need thereof’ is a female of child-bearing age, a peri- menopausal female, and / or a menopausal female.

[0065] As used herein, a “vaginal system” can be in a form of a vaginal ring (e.g., full ring or entire ring), and that these terms are sometimes used interchangeably throughout the disclosure, without limiting the scope of the disclosure.

[0066] In some embodiments, the vaginal system may include an outer ring layer having a first silicone polymer and a core having a second silicone polymer. In some embodiments, the first silicone polymer and the second silicone polymer are the same silicone polymer. In other embodiments, the first silicone polymer and the second silicone polymer are different from each other.

[0067] In some embodiments, the vaginal system comprises a core comprising a silicone polymer, a progestin, and barium sulfate (radiopaque ingredient) and is surrounded by a copolymer skin. In further embodiments, the core may also contain magnesium stearate. Insome embodiments, the core may comprise etonogestrel (ETO) as the progestin, such as from about 5% w / w etonogestrel to about 50% w / w etonogestrel.

[0068] Preferably, all of the progestin is in the core of the vaginal system. In some embodiments, a certain amount of the progestin may also be present in the outer ring layer, for example, as a result of migration from the core over time. Preferably, about 5 wt% or less, about 4 wt% or less, about 3 wt% or less, about 2 wt% or less, or about 1 wt% or less of the total amount of the progestin is in the outer ring.

[0069] As used herein, a “core diameter” of the vaginal system refers to a cross-sectional diameter of the drug loaded core. In embodiments, the core diameter is about uniform such that the core diameter is about the same length at any cross section along the drug loaded core. In embodiments, the core diameter varies such that cross sections of the drug loaded core have different core diameters.

[0070] As used herein, a “steady state release period” refers to a period where the vaginal system releases etonogestrel or any other progestin at a steady rate. Typically, a steady state release period is some significant number of days, such as 100 days, 200 days, 300 days, 365 days, 18 months, or 2 years, or any number therebetween, wherein the vaginal system steadily releases the progestin such that release rates per day do not rise, drop, and / or fluctuate significantly day by day.

[0071] As used herein, an “initial release period” refers to a period immediately after a vaginal system is implanted, wherein the release rate per day of a progestin is typically greater than the release rate per day during a steady state release period. As used herein, a “transition period” refers to a period immediately after the initial release period, wherein the release rate per day of the progestin decreases until the commencement of the steady state release period. For instance, immediately after a vaginal system is first positioned in the female, release rates per day of the progestin may have values greater than 40 pg per day for the first 0 to 7 days during the initial release period, but the release may decrease during the transition period for 7 to 28 days such that the release rate per day of the progestin is about 40 pg and remains 40 pg per day for during the steady state release period up to 24 months or up to about 365 days after the implantation of the vaginal system. A steady state release is a release of progestin during a steady state period.

[0072] As used herein, an “initial burst release” is the release of an amount of a progestin, such as etonogestrel, released before the steady state release period, such as the daily amount of release in the first several days immediately following implanting the vaginal system. The initial burst release does not occur during the transition period and / or thesteady state release period. Also, the initial burst release does not rise to the same level when the same vaginal system is reimplanted after removal during the steady state release period. In some embodiments, the initial burst release, after the vaginal system is stored for about 12-week, about 20-week, about 28-week, 12 months, 24 months, and / or 36 months post-production, or after the vaginal system is stored for greater than 0 months, greater than or equal to about 12-weeks, greater than or equal to about 20-weeks, greater than or equal to about 28-week, greater than or equal to about 12 months, greater than or equal to about 24 months, or greater than or equal to about 36 months post-production, does not exceed about 360 pg / day, such as never exceeding about 500 pg / day. about 490 pg / day, about 480 pg / day, about 470 pg / day, about 460 pg / day, about 450 pg / day, about 440 pg / day, about 430 pg / day, about 420 pg / day, about 410 pg / day, about 400 pg / day, about 390 pg / day, about 380 pg / day, about 370 pg / day, about 350 pg / day, about 340 pg / day, about 330 pg / day, about 320 pg / day, about 310 pg / day, about 300 pg / day, about 290 pg / day, about 280 pg / day, about 270 pg / day, about 260 pg / day, about 250 pg / day, about 240 pg / day, about 230 pg / day, about 220 pg / day, about 210 pg / day, or about 200 pg / day, or any number therebetween.

[0073] In some embodiments, estrogens may be used in addition to the progestin, including, for example, ethinyl estradiol, 17[3-estradiol, 17[3-estradiol-3 -acetate, mestranol, conjugated estrogens, USP and estrone or salts thereof.

[0074] In other embodiments, no estrogens are included in the vaginal system.

[0075] In some embodiments, progestins include, for example, progesterone and its derivatives such as 17-hydroxy progesterone esters and 19-or-17-hydroxy progesterone esters, 17-alpha-ethinyl testosterone, 17-alpha-ethinyl-19-nortestosterone (norethindrone) and derivatives thereof, norethindrone acetate, etonogestrel, norgestrel, nogestamate, desogestrel and D-17-beta-acetoxy-17-beta-ethyl-17-alpha-ethinyl-gon-4-en-3-one oxime. Other exemplary progestins include demegestone, drospirenone, dydrogesterone, gestodene, medrogestone, medroxy progesterone and esters thereof. In some embodiments, the amount of progestin used is described herein is “equivalent” in progestinic potency to an amount of etonogestrel. The equivalent progestinic potency of a progestin to etonogestrel may be readily determined by one of ordinary skill in the art.

[0076] In a preferred embodiment, etonogestrel is the progestin.

[0077] In a preferred embodiment, etonogestrel is the sole progestin.

[0078] In some embodiments, the vaginal system contains from about 10 mg to about 250 mg of progestin. In some embodiments, the vaginal system contains from about 10 mg toabout 100 mg of progestin, such as from about 5 mg to about 10 mg progestin, such as from about 5 mg to about 15 mg, from about 5 mg to about 20 mg, from about 5 mg to about 25 mg, from about 5 mg to about 30 mg, from about 5 mg to about 35 mg, from about 5 mg to about 40 mg, from about 5 mg to about 45 mg, from about 5 mg to about 50 mg, from about 5 mg to about 55 mg, from about 5 mg to about 60 mg, from about 5 mg to about 65 mg, from about 5 mg to about 70 mg, from about 5 mg to about 75 mg, from about 5 mg to about 80 mg, from about 5 mg to about 85 mg, from about 5 mg to about 90 mg, from about 5 mg to about 95 mg, from about 5 mg to about 100 mg, from about 10 mg to about 90 mg progestin, such as from about 10 mg to about 15 mg, from about 10 mg to about 20 mg, from about 10 mg to about 25 mg, from about 10 mg to about 30 mg, from about 10 mg to about 35 mg, from about 10 mg to about 40 mg, from about 10 mg to about 45 mg, from about 10 mg to about 50 mg, from about 10 mg to about 55 mg, from about 10 mg to about 60 mg, from about 10 mg to about 65 mg, from about 10 mg to about 70 mg, from about 10 mg to about 75 mg, from about 10 mg to about 80 mg, from about 10 mg to about 85 mg, from about 10 mg to about 90 mg, from about 10 mg to about 95 mg, from about 15 mg to about 20 mg, from about 15 mg to about 25 mg, from about 5 mg to about 30 mg, from about 15 mg to about 35 mg, from about 15 mg to about 40 mg, from about 15 mg to about 45mg, from about 15 mg to about 50 mg, from about 15 mg to about 55 mg, from about 15 mg to about 60 mg, from about 15 mg to about 65 mg, from about 15 mg to about 70 mg, from about 15 mg to about 75 mg, from about 15 mg to about 80 mg, from about 15 mg to about 85 mg, from about 15 mg to about 90 mg, from about 15 mg to about 95 mg, from about 15 mg to about 100 mg, from about 20 mg to about 25 mg, from about 20 mg to about 30 mg, from about 20 mg to about 35 mg, from about 20 mg to about 40 mg, from about 20 mg to about 45 mg, from about 20 mg to about 50 mg, from about 20 mg to about 55 mg, from about 20 mg to about 60 mg, from about 20 mg to about 65 mg, from about 20 mg to about 70 mg, from about 20 mg to about 75 mg, from about 20 mg to about 80 mg, from about 20 mg to about 85 mg, from about 20 mg to about 90 mg, from about 20 mg to about 95 mg, from about 20 mg to about 100 mg, from about 25 mg to about 30 mg, from about 25 mg to about 35 mg, from about 25 mg to about 40 mg, from about 25 mg to about 45 mg, from about 25 mg to about 50 mg, from about 25 mg to about 55 mg, from about 25 mg to about 60 mg, from about 25 mg to about 65 mg, from about 25 mg to about 70 mg, from about 25 mg to about 75 mg, from about 25 mg to about 80 mg, from about 25 mg to about 85 mg, from about 25 mg to about 90 mg, from about 25 mg to about 95 mg, from about 25 mg to about 100 mg, from about 30 mg to about 35 mg, from about 30 mg to about 40 mg,from about 30 mg to about 45 mg, from about 30 mg to about 50 mg, from about 30 mg to about 55 mg, from about 30 mg to about 60 mg, from about 30 mg to about 65 mg, from about 30 mg to about 70 mg, from about 30 mg to about 75 mg, from about 30 mg to about 80 mg, from about 30 mg to about 85 mg, from about 30 mg to about 90 mg, from about 30 mg to about 95 mg, from about 30 mg to about 100 mg, from about 35 mg to about 40 mg, from about 35 mg to about 45 mg, from about 35 mg to about 50 mg, from about 35 mg to about 55 mg, from about 35 mg to about 60 mg, from about 35 mg to about 65 mg, from about 35 mg to about 70 mg, from about 35 mg to about 75 mg, from about 35 mg to about 80 mg, from about 35 mg to about 85 mg, from about 35 mg to about 90 mg, from about 35 mg to about 95 mg, from about 35 mg to about 100 mg, from about 40 mg to about 45 mg, from about 40 mg to about 50 mg, from about 40 mg to about 55 mg, from about 40 mg to about 60 mg, from about 40 mg to about 65 mg, from about 40 mg to about 70 mg, from about 40 mg to about 75 mg, from about 40 mg to about 80 mg, from about 40 mg to about 85 mg, from about 40 mg to about 90 mg, from about 40 mg to about 95 mg, from about 40 mg to about 100 mg, from about 45 mg to about 50 mg, from about 45 mg to about 55 mg, from about 45 mg to about 60 mg, from about 45 mg to about 65 mg, from about 45 mg to about 70 mg, from about 45 mg to about 75 mg, from about 45 mg to about 80 mg, from about 45 mg to about 85 mg, from about 45 mg to about 90 mg, from about 45 mg to about 95 mg, from about 45 mg to about 100 mg, from about 50 mg to about 55 mg, from about 50 mg to about 60 mg, from about 50 mg to about 65 mg, from about 50 mg to about 70 mg, from about 60 mg to about 75 mg, from about 60 mg to about 80 mg, from about 60 mg to about 85 mg, from about 60 mg to about 90 mg, from about 60 mg to about 95 mg, from about 60 mg to about 100 mg, from about 65 mg to about 70 mg, from about 65 mg to about 75 mg, from about 65 mg to about 80 mg, from about 65 mg to about 85 mg, from about 65 mg to about 90 mg, from about 65 mg to about 95 mg, from about 65 mg to about 100 mg, from about 70 mg to about 75 mg, from about 70 mg to about 80 mg, from about 70 mg to about 85 mg, from about 70 mg to about 90 mg, from about 70 mg to about 95 mg, from about 70 mg to about 100 mg, from about 75 mg to about 80 mg, from about 75 mg to about 85 mg, from about 75 mg to about 90 mg, from about 75 mg to about 95 mg, from about 75 mg to about 100 mg, from about 80 mg to about 85 mg, from about 80 mg to about 90 mg, from about 80 mg to about 95 mg, from about 80 mg to about 100 mg, from about 85 mg to about 90 mg, from about 85 mg to about 95 mg, from about 85 mg to about 100 mg, from about 90 mg to about 95 mg, from about 90 mg to about 100 mg, or from about 95 mg to about 100 mg, or any number therebetween. Preferably, in these and other embodiments, atleast about 95 wt%, at least about 96 wt%, at least about 97 wt%, at least about 98 wt%, at least about 95 wt%, or about 100 wt% of the progestin is in the core.

[0079] Figure 1 depicts a top view of a vaginal system (100), according to an embodiment of the disclosure. Figure 2 depicts a cross-sectional view of a vaginal system (100), according to an embodiment of the disclosure.

[0080] In some embodiments, the vaginal system (100) has a channel (112) which accepts drug loaded cores (104), which are exemplified in Figures 1A, IB, and 2. The channel (112) may comprise one or more spaces in a torus body where one or more drug loaded cores (104) may be inserted. In some embodiments, vaginal system (100) may include one channel (112), or may be segmented or separated thereof to comprise multiple channels (112).

[0081] As shown in Figure 22, the vaginal system (100) is a soft, flexible ring that is positioned in an upper third (304) of a vagina, such as a female’s (300) vagina, either by a physician or a patient. Thus, the vaginal system (100) is independently implantable into a vagina (302) of the female by the female (300).

[0082] In some embodiments, the steady state release period of the progestin of the vaginal system (100) occurs up to about 24 months or up to about 365 days after placement of the vaginal system (100) in the female. In some embodiments, the steady state release period is from up to 24 months, from up to 23 months, from up to 22 months, from up to 21 months, from up to 20 months, from up to 19 months, from up to 18 months, from up to 17 months, from up to 16 months, from up to 15 months, from up to 14 months, from up to 13 months, or from up to 365 days, or any number therebetween, after placement of the vaginal system (100) in the female. In some embodiments, the steady state release period lasts from about 15 days to about 730 days, from about 15 days to about 50 days, from about 15 days to about 100 days, from about 15 days to about 150 days, from about 15 days to about 200 days, from about 15 days to about 250 days, from about 15 days to about 300 days, from about 15 days to about 350 days, from about 15 days to about 400 days, from about 15 days to about 450 days, from about 15 days to about 500 days, from about 15 days to about 550 days, from about 15 days to about 600 days, from about 15 days to about 650 days, from about 15 days to about 700 days, from about 50 days to about 100 days, from about 50 days to about 150 days, from about 50 days to about 200 days, from about 50 days to about 250 days, from about 50 days to about 300 days, from about 50 days to about 350 days, from about 50 days to about 400 days, from about 50 days to about 450 days, from about 50 days to about 500 days, from about 50 days to about 550 days, from about 50 days to about 600days, from about 50 days to about 650 days, from about 50 days to about 700 days, from about 50 days to about 730 days, from about 100 days to about 150 days, from about 100 days to about 200 days, from about 100 days to about 250 days, from about 100 days to about 300 days, from about 100 days to about 350 days, from about 100 days to about 400 days, from about 100 days to about 450 days, from about 100 days to about 500 days, from about 100 days to about 550 days, from about 100 days to about 600 days, from about 100 days to about 650 days, from about 100 days to about 700 days, from about 100 days to about 730 days, from about 150 days to about 200 days, from about 150 days to about 250 days, from about 150 days to about 300 days, from about 150 days to about 350 days, from about 150 days to about 400 days, from about 150 days to about 450 days, from about 150 days to about 500 days, from about 150 days to about 550 days, from about 150 days to about 600 days, from about 150 days to about 650 days, from about 150 days to about 700 days, from about 150 days to about 730 days, from about 200 days to about 250 days, from about 200 days to about 300 days, from about 200 days to about 350 days, from about 200 days to about 400 days, from about 200 days to about 450 days, from about 200 days to about 500 days, from about 200 days to about 550 days, from about 200 days to about 600 days, from about 200 days to about 650 days, from about 200 days to about 700 days, from about 200 days to about 730 days, from about 250 days to about 300 days, from about 250 days to about 350 days, from about 250 days to about 400 days, from about 250 days to about 450 days, from about 250 days to about 500 days, from about 250 days to about 550 days, from about 250 days to about 600 days, from about 250 days to about 650 days, from about 250 days to about 700 days, from about 250 days to about 730 days, from about 300 days to about 350 days, from about 300 days to about 400 days, from about 300 days to about 450 days, from about 300 days to about 500 days, from about 300 days to about 550 days, from about 300 days to about 600 days, from about 300 days to about 650 days, from about 300 days to about 700 days, from about 300 days to about 730 days, from about 350 days to about 400 days, from about 350 days to about 450 days, from about 350 days to about 500 days, from about 350 days to about 550 days, from about 350 days to about 600 days, from about 350 days to about 650 days, from about 350 days to about 700 days, from about 350 days to about 730 days, from about 400 days to about 450 days, from about 400 days to about 500 days, from about 400 days to about 550 days, from about 400 days to about 600 days, from about 400 days to about 650 days, from about 400 days to about 700 days, from about 400 days to about 730 days, from about 450 days to about 500 days, from about 450 days to about 550 days, from about 450 days to about 600 days, from about 450days to about 650 days, from about 450 days to about 700 days, from about 450 days to about 730 days, from about 500 days to about 550 days, from about 500 days to about 600 days, from about 500 days to about 650 days, from about 500 days to about 700 days, from about 500 days to about 730 days, from about 550 days to about 600 days, from about 550 days to about 650 days, from about 550 days to about 700 days, from about 550 days to about 730 days, from about 600 days to about 650 days, from about 600 days to about 700 days, from about 600 days to about 730 days, from about 650 days to about 700 days, from about 650 days to about 730 days, from about 700 days to about 730 days, or any number therebetween, after placement of the vaginal system (100) in the female.

[0083] In some embodiments, the steady state release period starts immediately after the transition period.

[0084] In some embodiments, the transition period starts immediately after the initial release period.

[0085] In some embodiments, the release per day of the progestin of the vaginal system (100) in the steady state release period is from about 10 pg / day to about 70 pg / day, such as from about 10 pg per day to about 15 pg per day, from about 10 pg per day to about 20 pg per day, from about 10 pg per day to about 25 pg per day, from about 10 pg per day to about 30 pg per day, from about 10 pg per day to about 35 pg per day, from about 10 pg per day to about 40 pg per day, from about 10 pg per day to about 45 pg per day, from about 10 pg per day to about 50 pg per day, from about 10 pg per day to about 55 pg per day, from about 10 pg per day to about 60 pg per day, from about 10 pg per day to about 65 pg per day, from about 15 pg per day to about 20 pg per day, from about 15 pg per day to about 25 pg per day, from about 15 pg per day to about 30 pg per day, from about 15 pg per day to about 35 pg per day, from about 15 pg per day to about 40 pg per day, from about 15 pg per day to about 45 pg per day, from about 15 pg per day to about 50 pg per day, from about 15 pg per day to about 55 pg per day, from about 15 pg per day to about 60 pg per day, from about 15 pg per day to about 65 pg per day, from about 15 pg per day to about 70 pg per day, from about 20 pg per day to about 25 pg per day, from about 20 pg per day to about 30 pg per day, from about 20 pg per day to about 35 pg per day, from about 20 pg per day to about 40 pg per day, from about 20 pg per day to about 45 pg per day, from about 20 pg per day to about 50 pg per day, from about 20 pg per day to about 55 pg per day, from about 20 pg per day to about 60 pg per day, from about 20 pg per day to about 65 pg per day, from about 20 pg per day to about 70 pg per day, from about 25 pg per day to about 30 pg per day, from about 25 pg per day to about 35 pg per day, fromabout 25 ig per day to about 40 pg per day, from about 25 pg per day to about 45 pg per day, from about 25 pg per day to about 50 pg per day, from about 25 pg per day to about 55 pg per day, from about 25 pg per day to about 60 pg per day, from about 25 pg per day to about 65 pg per day, from about 25 pg per day to about 70 pg per day, from about 30 pg per day to about 35 pg per day, from about 30 pg per day to about 40 pg per day, from about 30 pg per day to about 45 pg per day, from about 30 pg per day to about 50 pg per day, from about 30 pg per day to about 55 pg per day, from about 30 pg per day to about 60 pg per day, from about 35 pg per day to about 65 pg per day, from about 30 pg per day to about 70 pg per day, from about 35 pg per day to about 40 pg per day, from about 35 pg per day to about 45 pg per day, from about 35 pg per day to about 50 pg per day, from about 35 pg per day to about 55 pg per day, from about 35 pg per day to about 60 pg per day, from about 35 pg per day to about 65 pg per day, from about 35 pg per day to about 70 pg per day, from about 40 pg per day to about 45 pg per day, from about 40 pg per day to about 50 pg per day, from about 40 pg per day to about 55 pg per day, from about 40 pg per day to about 60 pg per day, from about 40 pg per day to about 65 pg per day, from about 40 pg per day to about 70 pg per day, from about 45 pg per day to about 50 pg per day, from about 45 pg per day to about 55 pg per day, from about 45 pg per day to about 60 pg per day, from about 45 pg per day to about 65 pg per day, from about 45 pg per day to about 70 pg per day, from about 50 pg per day to about 55 pg per day, from about 50 pg per day to about 60 pg per day, from about 50 pg per day to about 65 pg per day, from about 50 pg per day to about 70 pg per day, from about 55 pg per day to about 60 pg per day, from about 55 pg per day to about 65 pg per day, from about 55 pg per day to about 70 pg per day, from about 60 pg per day to about 65 pg per day, from about 60 pg per day to about 70 pg per day, or from about 65 pg per day to about 70 pg per day, or any number therebetween.

[0086] The initial release period of the progestin of the vaginal system (100) occurs from about 0 days to about 14 days after positioning the vaginal system (100) in the female, such as from about 0 days to about 1 day, from about 0 days to about 2 days, from about 0 days to about 3 days, from about 0 days to about 4 days, from about 0 days to about 5 days, from about 0 days to about 6 days, from about 0 days to about 7 days, from about 0 days to about 8 days, from about 0 days to about 9 days, from about 0 days to about 10 days, from about 0 days to about 11 day, from about 0 days to about 12 days, from about 0 days to about 13 days, from about 0 days to about 14 days, from about 1 day to about 2 days, from about 1 day to about 3 days, from about 1 day to about 4 days, from about 1 day to about 5 days,from about 1 day to about 6 days, from about 1 day to about 7 days, from about 1 day to about 8 days, from about 1 day to about 9 days, from about 1 day to about 10 days, from about 1 day to about 11 day, from about 1 day to about 12 days, from about 1 day to about 13 days, from about 1 day to about 14 days, from about 2 days to about 3 days, from about 2 days to about 4 days, from about 2 days to about 5 days, from about 2 days to about 6 days, from about 2 days to about 7 days, from about 2 days to about 8 days, from about 2 days to about 9 days, from about 2 days to about 10 days, from about 2 days to about 11 day, from about 2 days to about 12 days, from about 2 days to about 13 days, from about 2 days to about 14 days, from about 3 days to about 4 days, from about 3 days to about 5 days, from about 3 days to about 6 days, from about 3 days to about 7 days, from about 3 days to about 8 days, from about 3 days to about 9 days, from about 3 days to about 10 days, from about 3 days to about 11 day, from about 3 days to about 12 days, from about 3 days to about 13 days, from about 3 days to about 14 days, from about 4 days to about 5 days, from about 4 days to about 6 days, from about 4 days to about 7 days, from about 4 days to about 8 days, from about 4 days to about 9 days, from about 4 days to about 10 days, from about 4 days to about 11 day, from about 4 days to about 12 days, from about 4 days to about 13 days, from about 4 days to about 14 days, from about 5 days to about 6 days, from about 5 days to about 7 days, from about 5 days to about 8 days, from about 5 days to about 9 days, from about 5 days to about 10 days, from about 5 days to about 11 day, from about 5 days to about 12 days, from about 5 days to about 13 days, from about 5 days to about 14 days, from about 6 days to about 7 days, from about 6 days to about 8 days, from about 6 days to about 9 days, from about 6 days to about 10 days, from about 6 days to about 11 day, from about 6 days to about 12 days, from about 6 days to about 13 days, from about 6 days to about 14 days, from about 7 days to about 8 days, from about 7 days to about 9 days, from about 7 days to about 10 days, from about 7 days to about 11 day, from about 7 days to about 12 days, from about 7 days to about 13 days, from about 7 days to about 14 days, from about 8 days to about 9 days, from about 8 days to about 10 days, from about 8 days to about 11 day, from about 8 days to about 12 days, from about 8 days to about 13 days, from about 8 days to about 14 days, from about 9 days to about 10 days, from about 9 days to about 11 day, from about 9 days to about 12 days, from about 9 days to about 13 days, from about 9 days to about 14 days, from about 10 days to about 11 day, from about 10 days to about 12 days, from about 10 days to about 13 days, from about 10 days to about 14 days, from about 11 day to about 12 days, from about 11 day to about 13 days, from about 11 day to about 14 days, from about 12 days to about 13 days, fromabout 12 days to about 14 days, or from about 13 days to about 14 days, or any number therebetween.

[0087] The transition period of the vaginal system (100) occurs for about 7 days to about 28 days, such as for about 7 days to about 10 days, for about 7 days to about 13 days, for about 7 days to about 16 days, for about 7 days to about 19 days, for about 7 days to about 22 days, for about 7 days to about 25 days, for about 10 days to about 13 days, for about 10 days to about 16 days, for about 10 days to about 19 days, for about 10 days to about 22 days, for about 10 days to about 25 days, for about 10 days to about 28 days, for about 13 days to about 16 days, for about 13 days to about 19 days, for about 13 days to about 22 days, for about 13 days to about 25 days, for about 13 days to about 28 days, for about 16 days to about 19 days, for about 16 days to about 22 days, for about 16 days to about 25 days, for about 16 days to about 28 days, for about 19 days to about 22 days, for about 19 days to about 25 days, for about 19 days to about 28 days, for about 22 days to about 25 days, for about 22 days to about 28 days, or for about 25 days to about 28 days, or any number therebetween.

[0088] In preferred embodiments, the vaginal system (100) releases about 50 pg of a progestin per 24 hours consistently during a steady state release period, which may be up to 365 days or may be over 365 days.

[0089] In preferred embodiments, the vaginal system (100) releases about 45 pg of a progestin per 24 hours consistently during a steady state release period, which may be up to 365 days or may be over 365 days.

[0090] In preferred embodiments, the vaginal system (100) releases about 40 pg of a progestin per 24 hours consistently during a steady state release period, which may be up to 365 days or may be over 365 days.

[0091] In preferred embodiments, the vaginal system (100) releases about 35 pg of a progestin per 24 hours consistently during a steady state release period, which may be up to 365 days or may be over 365 days.

[0092] In preferred embodiments, the vaginal system (100) releases about 30 pg of a progestin per 24 hours consistently during a steady state release period, which may be up to 365 days or may be over 365 days.

[0093] In some embodiments, the vaginal system (100) releases etonogestrel at about 40 pg / day over at least about 365 days. In some embodiments, the vaginal system (100) releases etonogestrel at about 35 pg / day over at least about 365 days. In some embodiments, the vaginal system (100) releases etonogestrel at about 30 pg / day over atleast about 365 days. In some embodiments, the vaginal system is removed after about 24 months or about 365 days of continuous use.

[0094] In some embodiments, a drug release or an amount of etonogestrel released each day during the steady state release period is from about 30 pg to about 50 pg, such as 35 pg and 45 pg or such as 40 pg. In some embodiments, the amount of progestin or etonogestrel released each day during the steady state release period is from about 10 pg to about 100 pg, such as from about 30 pg to about 70 pg from about 30 pg to about 32 pg, from about 30 pg to about 34 pg, from about 30 pg to about 36 pg, from about 30 pg to about 38 pg, from about 30 pg to about 40 pg, from about 30 pg to about 42 pg, from about 30 pg to about 44 pg, from about 30 pg to about 46 pg, from about 30 pg to about 48 pg, from about 30 pg to about 50 pg, from about 30 pg to about 52 pg, from about 30 pg to about 54 pg, from about 30 pg to about 56 pg, from about 30 pg to about 58 pg, from about 30 pg to about 60 pg, from about 30 pg to about 62 pg, from about 30 pg to about 64 pg, from about 30 pg to about 66 pg, from about 30 pg to about 68 pg, from about 32 pg to about 34 pg, from about 32 pg to about 36 pg, from about 32 pg to about 38 pg, from about 32 pg to about 40 pg, from about 32 pg to about 42 pg, from about 32 pg to about 44 pg, from about 32 pg to about 46 pg, from about 32 pg to about 48 pg, from about 32 pg to about 50 pg, from about 32 pg to about 52 pg, from about 32 pg to about 54 pg, from about 32 pg to about 56 pg, from about 32 pg to about 58 pg, from about 32 pg to about 60 pg, from about 32 pg to about 62 pg, from about 32 pg to about 64 pg, from about 32 pg to about 66 pg, from about 32 pg to about 68 pg, from about 32 pg to about 70 pg, from about 34 pg to about 36 pg, from about 34 pg to about 38 pg, from about 34 pg to about 40 pg, from about 34 pg to about 42 pg, from about 34 pg to about 44 pg, from about 34 pg to about 46 pg, from about 34 pg to about 48 pg, from about 34 pg to about 50 pg, from about 34 pg to about 52 pg, from about 34 pg to about 54 pg, from about 34 pg to about 56 pg, from about 34 pg to about 58 pg, from about 34 pg to about 60 pg, from about 34 pg to about 62 pg, from about 34 pg to about 64 pg, from about 34 pg to about 66 pg, from about 34 pg to about 68 pg, from about 34 pg to about 70 pg, from about 36 pg to about 38 pg, from about 36 pg to about 40 pg, from about 36 pg to about 42 pg, from about 36 pg to about 44 pg, from about 36 pg to about 46 pg, from about 36 pg to about 48 pg, from about 36 pg to about 50 pg, from about 36 pg to about 52 pg, from about 36 pg to about 54 pg, from about 36 pg to about 56 pg, from about 36 pg to about 58 pg, from about 36 pg to about 60 pg, from about 36 pg to about 62 pg, from about 36 pg to about 64 pg, from about 36 pg to about 66 pg, from about 36 pg to about 68 pg, from about 36 pg to about 70 pg, from about38 ig to about 40 pig, from about 38 pig to about 42 pig, from about 38 pig to about 44 pig, from about 38 pig to about 46 pig, from about 38 pig to about 48 pig, from about 38 pig to about 50 pig, from about 38 pig to about 52 pig, from about 38 pig to about 54 pig, from about 38 pig to about 56 pig, from about 38 pig to about 58 pig, from about 38 pig to about 60 pig, from about 38 pig to about 62 pig, from about 38 pig to about 64 pig, from about 38 pig to about 66 pig, from about 38 pig to about 68 pig, from about 38 pig to about 70 pig, from about 40 pig to about 42 pig, from about 40 pig to about 44 pig, from about 40 pig to about 46 pig, from about 40 pig to about 48 pig, from about 40 pig to about 50 pig, from about 40 pig to about 52 pig, from about 40 pig to about 54 pig, from about 40 pig to about 56 pig, from about 40 pig to about 58 pig, from about 40 pig to about 60 pig, from about 40 pig to about 62 pig, from about 40 pig to about 64 pig, from about 40 pig to about 66 pig, from about 40 pig to about 68 pig, from about 40 pig to about 70 pig, from about 42 pig to about 44 pig, from about 42 pig to about 46 pig, from about 42 pig to about 48 pig, from about 42 pig to about 50 pig, from about 42 pig to about 52 pig, from about 42 pig to about 54 pig, from about 42 pig to about 56 pig, from about 42 pig to about 58 pig, from about 42 pig to about 60 pig, from about 42 pig to about 62 pig, from about 42 pig to about 64 pig, from about 42 pig to about 66 pig, from about 42 pig to about 68 pig, from about 42 pig to about 70 pig, from about 44 pig to about 46 pig, from about 44 pig to about 48 pig, from about 44 pig to about 50 pig, from about 44 pig to about 52 pig, from about 44 pig to about 54 pig, from about 44 pig to about 56 pig, from about 44 pig to about 58 pig, from about 44 pig to about 60 pig, from about 44 pig to about 62 pig, from about 44 pig to about 64 pig, from about 44 pig to about 66 pig, from about 44 pig to about 68 pig, from about 44 pig to about 70 pig, from about 46 pig to about 48 pig, from about 46 pig to about 50 pig, from about 46 pig to about 52 pig, from about 46 pig to about 54 pig, from about 46 pig to about 56 pig, from about 46 pig to about 58 pig, from about 46 pig to about 60 pig, from about 46 pig to about 62 pig, from about 46 pig to about 64 pig, from about 46 pig to about 66 pig, from about 46 pig to about 68 pig, from about 46 pig to about 70 pig, from about 48 pig to about 50 pig, from about 48 pig to about 52 pig, from about 48 pig to about 54 pig, from about 48 pig to about 56 pig, from about 48 pig to about 58 pig, from about 48 pig to about 60 pig, from about 48 pig to about 62 pig, from about 48 pig to about 64 pig, from about 48 pig to about 66 pig, from about 48 pig to about 68 pig, from about 48 pig to about 70 pig, from about 50 pig to about 52 pig, from about 50 pig to about 54 pig, from about 50 pig to about 56 pig, from about 50 pig to about 58 pig, from about 50 pig to about 60 pig, from about 50 pig to about 62 pig, from about 50 pig to about 64 pig, from about 50 pig to about 66 pig, from about 50 pig to about 68 pig, from about 50 pig to about 70 pig,from about 52 ig to about 54 pig, from about 52 pig to about 56 pig, from about 52 pig to about 58 pig, from about 52 pig to about 60 pig, from about 52 pig to about 62 pig, from about 52 pig to about 64 pig, from about 52 pig to about 66 pig, from about 52 pig to about 68 pig, from about 52 pig to about 70 pig, from about 54 pig to about 56 pig, from about 54 pig to about 58 pig, from about 54 pig to about 60 pig, from about 54 pig to about 62 pig, from about 54 pig to about 64 pig, from about 54 pig to about 66 pig, from about 54 pig to about 68 pig, from about 54 pig to about 70 pig, from about 56 pig to about 58 pig, from about 56 pig to about 60 pig, from about 56 pig to about 62 pig, from about 56 pig to about 64 pig, from about 56 pig to about 66 pig, from about 56 pig to about 68 pig, from about 56 pig to about 70 pig, from about 58 pig to about 60 pig, from about 58 pig to about 62 pig, from about 58 pig to about 64 pig, from about 58 pig to about 66 pig, from about 58 pig to about 68 pig, from about 58 pig to about 70 pig, from about 60 pig to about 62 pig, from about 60 pig to about 64 pig, from about 60 pig to about 66 pig, from about 60 pig to about 68 pig, from about 60 pig to about 70 pig, from about 62 pig to about 64 pig, from about 62 pig to about 66 pig, from about 62 pig to about 68 pig, from about 62 pig to about 70 pig, from about 64 pig to about 66 pig, from about 64 pig to about 68 pig, from about 64 pig to about 70 pig, from about 66 pig to about 68 pig, from about 66 pig to about 70 pig, from about 68 pig to about 70 pig, or any number therebetween.

[0095] In some embodiments, the amount of progestin or etonogestrel released each day during the steady state release period is from about 10 pg to about 160 pg, such as from about 10 pg to about 20 pg, from about 10 pg to about 30 pg, from about 10 pg to about 40 pg, from about 10 pg to about 50 pg, from about 10 pg to about 60 pg, from about 10 pg to about 70 pg, from about 10 pg to about 80 pg, from about 10 pg to about 90 pg, from about 10 pg to about 100 pg, from about 10 pg to about 110 pg, from about 10 pg to about 120 pg, from about 10 pg to about 130 pg, from about 10 pg to about 140 pg, from about 10 pg to about 150 pg, from about 20 pg to about 30 pg, from about 20 pg to about 40 pg, from about 20 pg to about 50 pg, from about 20 pg to about 60 pg, from about 20 pg to about 70 pg, from about 20 pg to about 80 pg, from about 20 pg to about 90 pg, from about 20 pg to about 100 pg, from about 20 pg to about 110 pg, from about 20 pg to about 120 pg, from about 20 pg to about 130 pg, from about 20 pg to about 140 pg, from about 20 pg to about 150 pg, from about 20 pg to about 160 pg, from about 30 pg to about 40 pg, from about 30 pg to about 50 pg, from about 30 pg to about 60 pg, from about 30 pg to about 70 pg, from about 30 pg to about 80 pg, from about 30 pg to about 90 pg, from about 30 pg to about 100 pg, from about 30 pg to about 110 pg, from about 30 pg to about 120 pg, from about30 ig to about 130 pig, from about 30 pig to about 140 pig, from about 30 pig to about 150 pig, from about 30 pig to about 160 pig, from about 40 pig to about 50 pig, from about 40 pig to about 60 pig, from about 40 pig to about 70 pig, from about 40 pig to about 80 pig, from about 40 pig to about 90 pig, from about 40 pig to about 100 pig, from about 40 pig to about 110 pig, from about 40 pig to about 120 pig, from about 40 pig to about 130 pig, from about 40 pig to about 140 pig, from about 40 pig to about 150 pig, from about 40 pig to about 160 pig, from about 50 pig to about 60 pig, from about 50 pig to about 70 pig, from about 50 pig to about 80 pig, from about 50 pig to about 90 pig, from about 50 pig to about 100 pig, from about 50 pig to about 110 pig, from about 50 pig to about 120 pig, from about 50 pig to about 130 pig, from about 50 pig to about 140 pig, from about 50 pig to about 150 pig, from about 50 pig to about 160 pig, from about 60 pig to about 70 pig, from about 60 pig to about 80 pig, from about 60 pig to about 90 pig, from about 60 pig to about 100 pig, from about 60 pig to about 110 pig, from about 60 pig to about 120 pig, from about 60 pig to about 130 pig, from about 60 pig to about 140 pig, from about 60 pig to about 150 pig, from about 60 pig to about 160 pig, from about 70 pig to about 80 pig, from about 70 pig to about 90 pig, from about 70 pig to about 100 pig, from about 70 pig to about 110 pig, from about 70 pig to about 120 pig, from about 70 pig to about 130 pig, from about 70 pig to about 140 pig, from about 70 pig to about 150 pig, from about 70 pig to about 160 pig, from about 80 pig to about 90 pig, from about 80 pig to about 100 pig, from about 80 pig to about 110 pig, from about 80 pig to about 120 pig, from about 80 pig to about 130 pig, from about 80 pig to about 140 pig, from about 80 pig to about 150 pig, from about 80 pig to about 160 pig, from about 90 pig to about 100 pig, from about 90 pig to about 110 pig, from about 90 pig to about 120 pig, from about 90 pig to about 130 pig, from about 90 pig to about 140 pig, from about 90 pig to about 150 pig, from about 90 pig to about 160 pig, from about 100 pig to about 110 pig, from about 100 pig to about 120 pig, from about 100 pig to about 130 pig, from about 100 pig to about 140 pig, from about 100 pig to about 150 pig, from about 100 pig to about 160 pig, from about 110 pig to about 120 pig, from about 110 pig to about 130 pig, from about 110 pig to about 140 pig, from about 110 pig to about 150 pig, from about 110 pig to about 160 pig, from about 120 pig to about 130 pig, from about 120 pig to about 140 pig, from about 120 pig to about 150 pig, from about 120 pig to about 160 pig, from about 130 pig to about 140 pig, from about 130 pig to about 150 pig, from about 130 pig to about 160 pig, from about 140 pig to about 150 pig, from about 140 pig to about 160 pig, from about 150 pig to about 160 pig, or any number therebetween.

[0096] In an embodiment, the vaginal system (100) may have an about circular shape, such that the torus body is an about circular torus shape. In other embodiments, vaginal system (100) may have an oblong shape, such that the torus body is an oblong torus shape.

[0097] In some embodiments, progestin is dispersed uniformly throughout the drug loaded cores (104).

[0098] In an embodiment, the torus body (102) controls the release of etonogestrel, such that the release of etonogestrel is slower than that of drug loaded cores (104) without the torus body (102). For example, embodiments of the disclosure having the drug loaded core (104) contained in the torus body (102) provide that the release rate of the progestin is about 40 pg per day while a drug loaded core (104) without a torus body (102) would have a release rate of greater than about 60 pg, about 80 pg, about 120 pg, about 160 pg, about 200 pg, or about 400 pg per day.

[0099] In some embodiments, the vaginal system (100) comprises a silicone polymer outer ring layer (or “sheath”) (or “torus body”) and a progestin drug loaded core (104). As known in the art, silicone polymer (or polysiloxane) is a polymer including repeating units of siloxane. Non-limiting examples of the silicone polymer include fluorosilicone, solid silicone rubber, and liquid silicone rubber. In some embodiments, the vaginal system (100) is pliable and / or odorless. In some embodiments, the outer ring layer (or “sheath”) (or “torus body”) comprises latex.

[0100] In some embodiments, the vaginal system (100) is a fully connected ring shape. In embodiments, the vaginal system (100) contains a drug loaded core (104), which can be an etonogestrel loaded core (104). In embodiments, the drug loaded core (104) is a full connected ring shape. In embodiments, the drug loaded core (104) may be split, such that the drug loaded core (104) has multiple cores (104) or such that the drug loaded core (104) is a partial ring, such as a half ring. Thus, in some embodiments, one or more cores (104) may be inserted into atorus body (102), and a core (104) runs along a full circumference of the torus body (102) or only a partial circumference of the torus body (102). In some embodiments, the vaginal system (100) may contain more than one drug loaded core (104), and each drug loaded core (104) has a length (“core length”) that may vary from core (104) to core (104). Further, each drug loaded core (104) may have a weight (“core weight”) that may vary from core (104) to core (104).

[0101] In some embodiments, the drug loaded core (104) may be cut, such that the drug loaded core (104) is cut into two pieces, such that the drug loaded core (104) is cut into three pieces, such that the drug loaded core (104) is cut into four pieces, such that the drugloaded core (104) is cut into five pieces, such that the drug loaded core (104) is cut into six pieces, such that the drug loaded core (104) is cut into seven pieces, such that the drug loaded core (104) is cut into eight pieces, or such that the drug loaded core (104) is cut into more than eight pieces.

[0102] In some embodiments, the vaginal system (100) comprises a silicone ring manufactured by injection molding (over-molding) a polymer, such as a silicone elastomer, over a drug loaded core (104) containing an excess of a progestin and a non-medicated silicone sheath.

[0103] In some embodiments, the vaginal system is, at least in part, manufactured by extrusion or injection molding a drug loaded polymeric drug loaded core (104), where the progestin is in excess, with a non-medicated polymeric sheath.

[0104] In some embodiments, the vaginal system (100) is at least in part manufactured by using a speed mixer for the manufacture of an elastomer mix. In embodiments, a rheometer may be used to gauge the viscosity of the elastomer mix to identify homogeneity of the elastomer mix.

[0105] In some embodiments, other mixers are used, including other mixers that allow for mass manufacture of the elastomer. In some embodiments, premixing of the elastomer mix is performed at a high speed such that the elastomer mix is less viscous and allow for the formation of a more homogeneous elastomer mix.

[0106] As shown in Figure 21, the active mix (200) is the mix that includes a progestin, such as the mix for creating a progestin-containing vaginal system (100) or, more specifically, an etonogestrel-containing vaginal system (100). Viscosity of the elastomer mix is directly proportional to a % drug loading of an active mix (200) containing the elastomer mix. For instance, an elastomer mix for an elastomer of the vaginal system may have a viscosity from 30,000 mPa- s to about 300,000 mPa s.

[0107] In some embodiments, an active mix (200) is prepared by adding the elastomer mix and the progestin in a mixing container, such as a cup. In embodiments, an active mix (200) is more specifically prepared by adding the elastomer mix and etonogestrel into a mixing container.

[0108] In some embodiments, half and / or full core rings (120) may be manufactured. In some embodiments, the core ring is an about circular shape. In embodiments, the core ring is an oblong shape. In embodiments, a core ring may be cut into various lengths, and cutting of the core ring may be done via a cutting device, such as a scalpel.

[0109] In aspects, once a half ring is produced, it may be quickly detabbed and placed into a full ring mold to produce a full ring.

[0110] In aspects, during the creation of the core ring (120), mold temperature may be kept constant at 80°C or from about 60°C to about 100°C, such as from about 60.0°C to about 62.5°C, from about 60.0°C to about 65.0°C, from about 60.0°C to about 67.5°C, from about 60.0°C to about 70.0°C, from about 60.0°C to about 72.5°C, from about 60.0°C to about 75.0°C, from about 60.0°C to about 77.5°C, from about 60.0°C to about 80.0°C, from about 60.0°C to about 82.5°C, from about 60.0°C to about 85.0°C, from about 60.0°C to about 87.5°C, from about 60.0°C to about 90.0°C, from about 60.0°C to about 92.5°C, from about 60.0°C to about 95.0°C, from about 60.0°C to about 97.5° C, from about 60.0°C to about 100°C, from about 62.5°C to about 65.0°C, from about 62.5°C to about 67.5°C, from about 62.5°C to about 70.0°C, from about 62.5°C to about 72.5°C, from about 62.5°C to about 75.0°C, from about 62.5°C to about 77.5°C, from about 62.5°C to about 80.0°C, from about 62.5°C to about 82.5°C, from about 62.5°C to about 85.0°C, from about 62.5°C to about 87.5°C, from about 62.5°C to about 90.0°C, from about 62.5°C to about 92.5°C, from about 62.5°C to about 95.0°C, from about 62.5°C to about 97.5° C, from about 62.5°C to about 100°C, from about 65.0°C to about 67.5°C, from about 65.0°C to about 70.0°C, from about 65.0°C to about 72.5°C, from about 65.0°C to about 75.0°C, from about 65.0°C to about 77.5°C, from about 65.0°C to about 80.0°C, from about 65.0°C to about 82.5°C, from about 65.0°C to about 85.0°C, from about 65.0°C to about 87.5°C, from about 65.0°C to about 90.0°C, from about 65.0°C to about 92.5°C, from about 65.0°C to about 95.0°C, from about 65.0°C to about 97.5° C, from about 65.0°C to about 100°C, from about 67.5°C to about 70.0°C, from about 67.5° C to about 72.5°C, from about 67.5° C to about 75.0°C, from about 67.5°C to about 77.5°C, from about 67.5° C to about 80.0°C, from about 67.5° C to about 82.5°C, from about 67.5° C to about 85.0°C, from about 67.5° C to about 87.5°C, from about 67.5°C to about 90.0°C, from about 67.5° C to about 92.5°C, from about 67.5° C to about 95.0°C, from about 67.5° C to about 97.5° C, from about 67.5° C to about 100°C, from about 70.0°C to about 72.5°C, from about 70.0°C to about 75.0°C, from about 70.0°C to about 77.5°C, from about 70.0°C to about 80.0°C, from about 70.0°C to about 82.5°C, from about 70.0°C to about 85.0°C, from about 70.0°C to about 87.5°C, from about 70.0°C to about 90.0°C, from about 70.0°C to about 92.5°C, from about 70.0°C to about 95.0°C, from about 70.0°C to about 97.5° C, from about 70.0°C to about 100°C, from about 72.5°C to about 75.0°C, from about 72.5°C to about 77.5°C, from about 72.5°C to about 80.0°C, from about 72.5°C to about 82.5°C, from about 72.5°C to about 85.0°C, from about 72.5°C toabout 87.5°C, from about 72.5°C to about 90.0°C, from about 72.5°C to about 92.5°C, from about 72.5°C to about 95.0°C, from about 72.5°C to about 97.5° C, from about 72.5°C to about 100°C, from about 75.0°C to about 77.5°C, from about 75.0°C to about 80.0°C, from about 75.0°C to about 82.5°C, from about 75.0°C to about 85.0°C, from about 75.0°C to about 87.5°C, from about 75.0°C to about 90.0°C, from about 75.0°C to about 92.5°C, from about 75.0°C to about 95.0°C, from about 75.0°C to about 97.5° C, from about 75.0°C to about 100°C, from about 77.5°C to about 80.0°C, from about 77.5°C to about 82.5°C, from about 77.5°C to about 85.0°C, from about 77.5°C to about 87.5°C, from about 77.5° C to about 90.0°C, from about 77.5° C to about 92.5°C, from about 77.5°C to about 95.0°C, from about 77.5°C to about 97.5° C, from about 77.5°C to about 100°C, from about 80.0°C to about 82.5°C, from about 80.0°C to about 85.0°C, from about 80.0°C to about 87.5°C, from about 80.0°C to about 90.0°C, from about 80.0°C to about 92.5°C, from about 80.0°C to about 95.0°C, from about 80.0°C to about 97.5°C, from about 80.0°C to about 100°C, from about 82.5°C to about 85.0°C, from about 82.5°C to about 87.5°C, from about 82.5°C to about 90.0°C, from about 82.5°C to about 92.5°C, from about 82.5°C to about 95.0°C, from about 82.5°C to about 97.5° C, from about 82.5°C to about 100°C, from about 85.0°C to about 87.5°C, from about 85.0°C to about 90.0°C, from about 85.0°C to about 92.5°C, from about 85.0°C to about 95.0°C, from about 85.0°C to about 97.5° C, from about 85.0°C to about 100°C, from about 87.5°C to about 90.0°C, from about 87.5°C to about 92.5°C, from about 87.5°C to about 95.0°C, from about 87.5°C to about 97.5° C, from about 87.5°C to about 100°C, from about 90.0°C to about 92.5°C, from about 90.0°C to about 95.0°C, from about 90.0°C to about 97.5° C, from about 90.0°C to about 100°C, from about 92.5°C to about 95.0°C, from about 92.5°C to about 97.5° C, from about 92.5°C to about 100°C, from about 95.0°C to about 97.5° C, from about 95.0°C to about 100°C, or from about 97.5° C to about 100°C, or any number therebetween.

[0111] In some embodiments, curing time for the core ring (120) manufacture may be about 5 s to 60 s, such as about from about 5 s to about 10 s, from about 5 s to about 15 s, from about 5 s to about 20 s, from about 5 s to about 25 s, from about 5 s to about 30 s, from about 5 s to about 35 s, from about 5 s to about 40 s, from about 5 s to about 45 s, from about 5 s to about 50 s, from about 5 s to about 55 s, from about 10 s to about 15 s, from about 10 s to about 20 s, from about 10 s to about 25 s, from about 10 s to about 30 s, from about 10 s to about 35 s, from about 10 s to about 40 s, from about 10 s to about 45 s, from about 10 s to about 50 s, from about 10 s to about 55 s, from about 10 s to about 60 s, from about 15 s to about 20 s, from about 15 s to about 25 s, from about 15 s to about 30 s,from about 15 s to about 35 s, from about 15 s to about 40 s, from about 15 s to about 45 s, from about 15 s to about 50 s, from about 15 s to about 55 s, from about 15 s to about 60 s, from about 20 s to about 25 s, from about 20 s to about 30 s, from about 20 s to about 35 s, from about 20 s to about 40 s, from about 20 s to about 45 s, from about 20 s to about 50 s, from about 20 s to about 55 s, from about 20 s to about 60 s, from about 25 s to about 30 s, from about 25 s to about 35 s, from about 25 s to about 40 s, from about 25 s to about 45 s, from about 25 s to about 50 s, from about 25 s to about 55 s, from about 25 s to about 60 s, from about 30 s to about 35 s, from about 30 s to about 40 s, from about 30 s to about 45 s, from about 30 s to about 50 s, from about 30 s to about 55 s, from about 30 s to about 60 s, from about 35 s to about 40 s, from about 35 s to about 45 s, from about 35 s to about 50 s, from about 35 s to about 55 s, from about 35 s to about 60 s, from about 40 s to about 45 s, from about 40 s to about 50 s, from about 40 s to about 55 s, from about 40 s to about 60 s, from about 45 s to about 50 s, from about 45 s to about 55 s, from about 45 s to about 60 s, from about 50 s to about 55 s, from about 50 s to about 60 s, from about 55 s to about 60 s, or any number therebetween.

[0112] In other embodiments, curing time for the core ring (120) manufacture may be about 60 s to about 240 s, such as about 60 s, about 120 s, about 180 s, or about 240 s. In aspects, curing time for the core ring (120) manufacture may be from about 60 s to about 260 s, such as from about 60 s to about 70 s, from about 60 s to about 80 s, from about 60 s to about 90 s, from about 60 s to about 100 s, from about 60 s to about 110 s, from about 60 s to about 120 s, from about 60 s to about 130 s, from about 60 s to about 140 s, from about 60 s to about 150 s, from about 60 s to about 160 s, from about 60 s to about 170 s, from about 60 s to about 180 s, from about 60 s to about 190 s, from about 60 s to about 200 s, from about 60 s to about 210 s, from about 60 s to about 220 s, from about 60 s to about 230 s, from about 60 s to about 240 s, from about 60 s to about 250 s, from about 70 s to about 80 s, from about 70 s to about 90 s, from about 70 s to about 100 s, from about 70 s to about 110 s, from about 70 s to about 120 s, from about 70 s to about 130 s, from about 70 s to about 140 s, from about 70 s to about 150 s, from about 70 s to about 160 s, from about 70 s to about 170 s, from about 70 s to about 180 s, from about 70 s to about 190 s, from about 70 s to about 200 s, from about 70 s to about 210 s, from about 70 s to about 220 s, from about 70 s to about 230 s, from about 70 s to about 240 s, from about 70 s to about 250 s, from about 70 s to about 260 s, from about 80 s to about 90 s, from about 80 s to about 100 s, from about 80 s to about 110 s, from about 80 s to about 120 s, from about 80 s to about 130 s, from about 80 s to about 140 s, from about 80 s to about 150 s, from about 80 s toabout 160 s, from about 80 s to about 170 s, from about 80 s to about 180 s, from about 80 s to about 190 s, from about 80 s to about 200 s, from about 80 s to about 210 s, from about 80 s to about 220 s, from about 80 s to about 230 s, from about 80 s to about 240 s, from about 80 s to about 250 s, from about 80 s to about 260 s, from about 90 s to about 100 s, from about 90 s to about 110 s, from about 90 s to about 120 s, from about 90 s to about 130 s, from about 90 s to about 140 s, from about 90 s to about 150 s, from about 90 s to about 160 s, from about 90 s to about 170 s, from about 90 s to about 180 s, from about 90 s to about 190 s, from about 90 s to about 200 s, from about 90 s to about 210 s, from about 90 s to about 220 s, from about 90 s to about 230 s, from about 90 s to about 240 s, from about 90 s to about 250 s, from about 90 s to about 260 s, from about 100 s to about 110 s, from about 100 s to about 120 s, from about 100 s to about 130 s, from about 100 s to about 140 s, from about 100 s to about 150 s, from about 100 s to about 160 s, from about 100 s to about 170 s, from about 100 s to about 180 s, from about 100 s to about 190 s, from about 100 s to about 200 s, from about 100 s to about 210 s, from about 100 s to about 220 s, from about 100 s to about 230 s, from about 100 s to about 240 s, from about 100 s to about 250 s, from about 100 s to about 260 s, from about 110 s to about 120 s, from about 110 s to about 130 s, from about 110 s to about 140 s, from about 110 s to about 150 s, from about 110 s to about 160 s, from about 110 s to about 170 s, from about 110 s to about 180 s, from about 110 s to about 190 s, from about 110 s to about 200 s, from about 110 s to about 210 s, from about 110 s to about 220 s, from about 110 s to about 230 s, from about 110 s to about 240 s, from about 110 s to about 250 s, from about 110 s to about 260 s, from about 120 s to about 130 s, from about 120 s to about 140 s, from about 120 s to about 150 s, from about 120 s to about 160 s, from about 120 s to about 170 s, from about 120 s to about 180 s, from about 120 s to about 190 s, from about 120 s to about 200 s, from about 120 s to about 210 s, from about 120 s to about 220 s, from about 120 s to about 230 s, from about 120 s to about 240 s, from about 120 s to about 250 s, from about 120 s to about 260 s, from about 130 s to about 140 s, from about 130 s to about 150 s, from about 130 s to about 160 s, from about 130 s to about 170 s, from about 130 s to about 180 s, from about 130 s to about 190 s, from about 130 s to about 200 s, from about 130 s to about 210 s, from about 130 s to about 220 s, from about 130 s to about 230 s, from about 130 s to about 240 s, from about 130 s to about 250 s, from about 130 s to about 260 s, from about 140 s to about 150 s, from about 140 s to about 160 s, from about 140 s to about 170 s, from about 140 s to about 180 s, from about 140 s to about 190 s, from about 140 s to about 200 s, from about 140 s to about 210 s, from about 140 s to about 220 s, from about 140 s to about 230 s, fromabout 140 s to about 240 s, from about 140 s to about 250 s, from about 140 s to about 260 s, from about 150 s to about 160 s, from about 150 s to about 170 s, from about 150 s to about 180 s, from about 150 s to about 190 s, from about 150 s to about 200 s, from about 150 s to about 210 s, from about 150 s to about 220 s, from about 150 s to about 230 s, from about 150 s to about 240 s, from about 150 s to about 250 s, from about 150 s to about 260 s, from about 160 s to about 170 s, from about 160 s to about 180 s, from about 160 s to about 190 s, from about 160 s to about 200 s, from about 160 s to about 210 s, from about 160 s to about 220 s, from about 160 s to about 230 s, from about 160 s to about 240 s, from about 160 s to about 250 s, from about 160 s to about 260 s, from about 170 s to about 180 s, from about 170 s to about 190 s, from about 170 s to about 200 s, from about 170 s to about 210 s, from about 170 s to about 220 s, from about 170 s to about 230 s, from about 170 s to about 240 s, from about 170 s to about 250 s, from about 170 s to about 260 s, from about 180 s to about 190 s, from about 180 s to about 200 s, from about 180 s to about 210 s, from about 180 s to about 220 s, from about 180 s to about 230 s, from about 180 s to about 240 s, from about 180 s to about 250 s, from about 180 s to about 260 s, from about 190 s to about 200 s, from about 190 s to about 210 s, from about 190 s to about 220 s, from about 190 s to about 230 s, from about 190 s to about 240 s, from about 190 s to about 250 s, from about 190 s to about 260 s, from about 200 s to about 210 s, from about 200 s to about 220 s, from about 200 s to about 230 s, from about 200 s to about 240 s, from about 200 s to about 250 s, from about 200 s to about 260 s, from about 210 s to about 220 s, from about 210 s to about 230 s, from about 210 s to about 240 s, from about 210 s to about 250 s, from about 210 s to about 260 s, from about 220 s to about 230 s, from about 220 s to about 240 s, from about 220 s to about 250 s, from about 220 s to about 260 s, from about 230 s to about 240 s, from about 230 s to about 250 s, from about 230 s to about 260 s, from about 240 s to about 250 s, from about 240 s to about 260 s, from about 250 s to about 260 s, or any number therebetween. A cure time of 120 s may result in core rings (120) that are non-tacky and easy to remove from the mold.

[0113] To prepare a core ring (120), from about 40 g to about 50 g of the active mix (200) may be used, and from about 0.1 g to about 0. 125 g of catalyst (e.g., Stannous Octoate) may be used, such that the active-mix:catalyst (e.g., Stannous Octoate) ratio is from about 400: 1 to about 500: 1. One skilled in the relevant art would recognize that the amounts of components used may be upscaled for commercial purposes. In some embodiments, the active-mix:catalyst (e.g., Stannous Octoate) ratio may be from about 100: 1 to about 500: 1, such as from about 100: 1 to about 500: 1, from about 120: 1 to about 500: 1, from about130: 1 to about 500: 1, from about 140: 1 to about 500: 1, from about 150: 1 to about 500: 1, from about 160: 1 to about 500: 1, from about 170: 1 to about 500: 1, from about 180: 1 to about 500: 1, from about 190: 1 to about 500: 1, from about 200: 1 to about 220: 1, from about 200: 1 to about 240: 1, from about 200: 1 to about 260: 1, from about 200: 1 to about 280: 1, from about 200: 1 to about 300: 1, from about 200: 1 to about 320: 1, from about 200: 1 to about 340: 1, from about 200: 1 to about 360: 1, from about 200: 1 to about 380: 1, from about 200: 1 to about 400: 1, from about 200: 1 to about 420: 1, from about 200: 1 to about 440: 1, from about 200: 1 to about 460: 1, from about 200: 1 to about 480: 1, from about 200: 1 to about 500: 1, from about 220: 1 to about 240: 1, from about 220: 1 to about 260: 1, from about 220: 1 to about 280: 1, from about 220: 1 to about 300: 1, from about 220: 1 to about 320: 1, from about 220: 1 to about 340: 1, from about 220: 1 to about 360: 1, from about 220: 1 to about 380: 1, from about 220: 1 to about 400: 1, from about 220: 1 to about 420: 1, from about 220: 1 to about 440: 1, from about 220: 1 to about 460: 1, from about 220: 1 to about 480: 1, from about 220: 1 to about 500: 1, from about 240: 1 to about 260: 1, from about 240: 1 to about 280: 1, from about 240: 1 to about 300: 1, from about 240: 1 to about 320: 1, from about 240: 1 to about 340: 1, from about 240: 1 to about 360: 1, from about 240: 1 to about 380: 1, from about 240: 1 to about 400: 1, from about 240: 1 to about 420: 1, from about 240: 1 to about 440: 1, from about 240: 1 to about 460: 1, from about 240: 1 to about 480: 1, from about 240: 1 to about 500: 1, from about 260: 1 to about 280: 1, from about 260: 1 to about 300: 1, from about 260: 1 to about 320: 1, from about 260: 1 to about 340: 1, from about 260: 1 to about 360: 1, from about 260: 1 to about 380: 1, from about 260: 1 to about 400: 1, from about 260: 1 to about 420: 1, from about 260: 1 to about 440: 1, from about 260: 1 to about 460: 1, from about 260: 1 to about 480: 1, from about 260: 1 to about 500: 1, from about 280: 1 to about 300: 1, from about 280: 1 to about 320: 1, from about 280: 1 to about 340: 1, from about 280: 1 to about 360: 1, from about 280: 1 to about 380: 1, from about 280: 1 to about 400: 1, from about 280: 1 to about 420: 1, from about 280: 1 to about 440: 1, from about 280: 1 to about 460: 1, from about 280: 1 to about 480: 1, from about 280: 1 to about 500: 1, from about 300: 1 to about 320: 1, from about 300: 1 to about 340: 1, from about 300: 1 to about 360: 1, from about 300: 1 to about 380: 1, from about 300: 1 to about 400: 1, from about 300: 1 to about 420: 1, from about 300: 1 to about 440: 1, from about 300: 1 to about 460: 1, from about 300: 1 to about 480: 1, from about 300: 1 to about 500: 1, from about 320: 1 to about 340: 1, from about 320: 1 to about 360: 1, from about 320: 1 to about 380: 1, from about 320: 1 to about 400: 1, from about 320: 1 to about 420: 1, from about 320: 1 to about 440: 1, from about 320: 1 to about 460: 1, from about 320: 1 to about 480: 1, from about 320: 1 to about 500: 1,from about 340: 1 to about 360: 1, from about 340: 1 to about 380: 1, from about 340: 1 to about 400: 1, from about 340: 1 to about 420: 1, from about 340: 1 to about 440: 1, from about 340: 1 to about 460: 1, from about 340: 1 to about 480: 1, from about 340: 1 to about 500: 1, from about 360: 1 to about 380: 1, from about 360: 1 to about 400: 1, from about 360: 1 to about 420: 1, from about 360: 1 to about 440: 1, from about 360: 1 to about 460: 1, from about 360: 1 to about 480: 1, from about 360: 1 to about 500: 1, from about 380: 1 to about 400: 1, from about 380: 1 to about 420: 1, from about 380: 1 to about 440: 1, from about 380: 1 to about 460: 1, from about 380: 1 to about 480: 1, from about 380: 1 to about 500: 1, from about 400: 1 to about 420: 1, from about 400: 1 to about 440: 1, from about 400: 1 to about 460: 1, from about 400: 1 to about 480: 1, from about 400: 1 to about 500: 1, from about 420: 1 to about 440: 1, from about 420: 1 to about 460: 1, from about 420: 1 to about 480: 1, from about 420: 1 to about 500: 1, from about 440: 1 to about 460: 1, from about 440: 1 to about 480: 1, from about 440: 1 to about 500: 1, from about 460: 1 to about 480: 1, from about 460: 1 to about 500: 1, from about 480: 1 to about 500: 1, or any number therebetween.

[0114] In some embodiments, a catalyzed active mix (202), as shown in Figure 21, may be injected into the core ring (120) mold.

[0115] In some embodiments, the cure time of the core ring manufacture with the active mix (200) may be about 120 s, or from about 60 s to about 180 s, such as from about 60 s to about 70 s, from about 60 s to about 80 s, from about 60 s to about 90 s, from about 60 s to about 100 s, from about 60 s to about 110 s, from about 60 s to about 120 s, from about 60 s to about 130 s, from about 60 s to about 140 s, from about 60 s to about 150 s, from about 60 s to about 160 s, from about 60 s to about 170 s, from about 70 s to about 80 s, from about 70 s to about 90 s, from about 70 s to about 100 s, from about 70 s to about 110 s, from about 70 s to about 120 s, from about 70 s to about 130 s, from about 70 s to about 140 s, from about 70 s to about 150 s, from about 70 s to about 160 s, from about 70 s to about 170 s, from about 70 s to about 180 s, from about 80 s to about 90 s, from about 80 s to about 100 s, from about 80 s to about 110 s, from about 80 s to about 120 s, from about 80 s to about 130 s, from about 80 s to about 140 s, from about 80 s to about 150 s, from about 80 s to about 160 s, from about 80 s to about 170 s, from about 80 s to about 180 s, from about 90 s to about 100 s, from about 90 s to about 110 s, from about 90 s to about 120 s, from about 90 s to about 130 s, from about 90 s to about 140 s, from about 90 s to about 150 s, from about 90 s to about 160 s, from about 90 s to about 170 s, from about 90 s to about 180 s, from about 100 s to about 110 s, from about 100 s to about 120 s, from about 100 s to about 130 s, from about 100 s to about 140 s, from about 100 s to about 150 s, from about100 s to about 160 s, from about 100 s to about 170 s, from about 100 s to about 180 s, from about 110 s to about 120 s, from about 110 s to about 130 s, from about 110 s to about 140 s, from about 110 s to about 150 s, from about 110 s to about 160 s, from about 110 s to about 170 s, from about 110 s to about 180 s, from about 120 s to about 130 s, from about 120 s to about 140 s, from about 120 s to about 150 s, from about 120 s to about 160 s, from about 120 s to about 170 s, from about 120 s to about 180 s, from about 130 s to about 140 s, from about 130 s to about 150 s, from about 130 s to about 160 s, from about 130 s to about 170 s, from about 130 s to about 180 s, from about 140 s to about 150 s, from about 140 s to about 160 s, from about 140 s to about 170 s, from about 140 s to about 180 s, from about 150 s to about 160 s, from about 150 s to about 170 s, from about 150 s to about 180 s, from about 160 s to about 170 s, from about 160 s to about 180 s, from about 170 s to about 180 s, or any number therebetween.

[0116] In some embodiments, the entire ring may have a full ring weight of about 7.7 g or 9.9 g. In some embodiments, the entire ring may have a full ring weight ranging from about 7.7 g to about 9.9 g, from about 7.5 g to about 10 g, or from about 5 g to about 12 g, such as from about 5.0 g to about 5.5 g, from about 5.0 g to about 6.0 g, from about 5.0 g to about6.5 g, from about 5.0 g to about 7.0 g, from about 5.0 g to about 7.5 g, from about 5.0 g to about 8.0 g, from about 5.0 g to about 8.5 g, from about 5.0 g to about 9.0 g, from about 5.0 g to about 9.5 g, from about 5.0 g to about 10.0 g, from about 5.0 g to about 10.5 g, from about 5.0 g to about 11.0 g, from about 5.0 g to about 11.5 g, from about 5.5 g to about 6.0 g, from about 5.5 g to about 6.5 g, from about 5.5 g to about 7.0 g, from about 5.5 g to about7.5 g, from about 5.5 g to about 8.0 g, from about 5.5 g to about 8.5 g, from about 5.5 g to about 9.0 g, from about 5.5 g to about 9.5 g, from about 5.5 g to about 10.0 g, from about5.5 g to about 10.5 g, from about 5.5 g to about 11.0 g, from about 5.5 g to about 11.5 g, from about 5.5 g to about 12.0 g, from about 6.0 g to about 6.5 g, from about 6.0 g to about 7.0 g, from about 6.0 g to about 7.5 g, from about 6.0 g to about 8.0 g, from about 6.0 g to about 8.5 g, from about 6.0 g to about 9.0 g, from about 6.0 g to about 9.5 g, from about 6.0 g to about 10.0 g, from about 6.0 g to about 10.5 g, from about 6.0 g to about 11.0 g, from about 6.0 g to about 11.5 g, from about 6.0 g to about 12.0 g, from about 6.5 g to about 7.0 g, from about 6.5 g to about 7.5 g, from about 6.5 g to about 8.0 g, from about 6.5 g to about8.5 g, from about 6.5 g to about 9.0 g, from about 6.5 g to about 9.5 g, from about 6.5 g to about 10.0 g, from about 6.5 g to about 10.5 g, from about 6.5 g to about 11.0 g, from about6.5 g to about 11.5 g, from about 6.5 g to about 12.0 g, from about 7.0 g to about 7.5 g, from about 7.0 g to about 8.0 g, from about 7.0 g to about 8.5 g, from about 7.0 g to about9.0 g, from about 7.0 g to about 9.5 g, from about 7.0 g to about 10.0 g, from about 7.0 g to about 10.5 g, from about 7.0 g to about 11.0 g, from about 7.0 g to about 11.5 g, from about 7.0 g to about 12.0 g, from about 7.5 g to about 8.0 g, from about 7.5 g to about 8.5 g, from about 7.5 g to about 9.0 g, from about 7.5 g to about 9.5 g, from about 7.5 g to about 10.0 g, from about 7.5 g to about 10.5 g, from about 7.5 g to about 11.0 g, from about 7.5 g to about11.5 g, from about 7.5 g to about 12.0 g, from about 8.0 g to about 8.5 g, from about 8.0 g to about 9.0 g, from about 8.0 g to about 9.5 g, from about 8.0 g to about 10.0 g, from about 8.0 g to about 10.5 g, from about 8.0 g to about 11.0 g, from about 8.0 g to about 11.5 g, from about 8.0 g to about 12.0 g, from about 8.5 g to about 9.0 g, from about 8.5 g to about9.5 g, from about 8.5 g to about 10.0 g, from about 8.5 g to about 10.5 g, from about 8.5 g to about 11.0 g, from about 8.5 g to about 11.5 g, from about 8.5 g to about 12.0 g, from about 9.0 g to about 9.5 g, from about 9.0 g to about 10.0 g, from about 9.0 g to about 10.5 g, from about 9.0 g to about 11.0 g, from about 9.0 g to about 11.5 g, from about 9.0 g to about 12.0 g, from about 9.5 g to about 10.0 g, from about 9.5 g to about 10.5 g, from about9.5 g to about 11.0 g, from about 9.5 g to about 11.5 g, from about 9.5 g to about 12.0 g, from about 10.0 g to about 10.5 g, from about 10.0 g to about 11.0 g, from about 10.0 g to about 11.5 g, from about 10.0 g to about 12.0 g, from about 10.5 g to about 11.0 g, from about 10.5 g to about 11.5 g, from about 10.5 g to about 12.0 g, from about 11.0 g to about11.5 g, from about 11.0 g to about 12.0 g, from about 11.5 g to about 12.0 g, or any number therebetween.

[0117] In some embodiments, the full ring weight is from about 7.1 g to about 8.3 g, such as from about 7.1 g to about 7.2 g, from about 7. 1 g to about 7.4 g, from about 7.1 g to about 7.6 g, from about 7.1 g to about 7.8 g, from about 7.1 g to about 8.0 g, from about 7. 1 g to about 8.2 g, from about 7.2 g to about 7.4 g, from about 7.2 g to about 7.6 g, from about7.2 g to about 7.8 g, from about 7.2 g to about 8.0 g, from about 7.2 g to about 8.2 g, from about 7.2 g to about 8.3 g, from about 7.4 g to about 7.6 g, from about 7.4 g to about 7.8 g, from about 7.4 g to about 8.0 g, from about 7.4 g to about 8.2 g, from about 7.4 g to about8.3 g, from about 7.6 g to about 7.8 g, from about 7.6 g to about 8.0 g, from about 7.6 g to about 8.2 g, from about 7.6 g to about 8.3 g, from about 7.8 g to about 8.0 g, from about 7.8 g to about 8.2 g, from about 7.8 g to about 8.3 g, from about 8.0 g to about 8.2 g, from about 8.0 g to about 8.3 g, from about 8.2 g to about 8.3 g, or any number therebetween. In some embodiments, the full ring weight is about 7.7 g.

[0118] In some embodiments, full ring weight is from about 9.3 g to about 10.5 g. In some embodiments, the full ring weight is about 9.9 g. In some embodiments, the full ringweight is from about 0.1 g to about 20.0 g, including from about 9.3 g to about 10.5 g when comparing no. of cores (104) to core weight in grams, such as from about 9.3 g to about 9.5 g, from about 9.3 g to about 9.7 g, from about 9.3 g to about 9.9 g, from about 9.3 g to about 10.1 g, from about 9.3 g to about 10.3 g, from about 9.5 g to about 9.7 g, from about 9.5 g to about 9.9 g, from about 9.5 g to about 10.1 g, from about 9.5 g to about 10.3 g, from about 9.5 g to about 10.5 g, from about 9.7 g to about 9.9 g, from about 9.7 g to about 10.1 g, from about 9.7 g to about 10.3 g, from about 9.7 g to about 10.5 g, from about 9.9 g to about 10. 1 g, from about 9.9 g to about 10.3 g, from about 9.9 g to about 10.5 g, from about 10.1 g to about 10.3 g, from about 10.1 g to about 10.5 g, or from about 10.3 g to about 10.5 g, or any number therebetween.

[0119] Drug loaded cores (104) may be cut to specific lengths and weighed in accordance with an In Process Control (IPC) method. Drug loaded cores (104) may be from about 485 mg to about 515 mg in weight or from about 30 mg to about 300 mg in weight, about 30 mg to about 700 mg in weight, or from about 48 mg to about 520 mg in weight, such as from about 48 mg to about 490 mg, from about 48 mg to about 500 mg, from about 48 mg to about 510 mg, from about 48 mg to about 520 mg, from about 49 mg to about 500 mg, from about 49 mg to about 510 mg, from about 49 mg to about 520 mg, from about 50 mg to about 510 mg, from about 50 mg to about 520 mg, or from about or 51 mg to about 520 mg, about 300 mg to about 700 mg in weight or from about 480 mg to about 520 mg in weight, such as from about 480 mg to about 490 mg, from about 480 mg to about 500 mg, from about 480 mg to about 510 mg, from about 480 mg to about 520 mg, from about 490 mg to about 500 mg, from about 490 mg to about 510 mg, from about 490 mg to about 520 mg, from about 500 mg to about 510 mg, from about 500 mg to about 520 mg, or from about or 510 mg to about 520 mg, or any number therebetween.

[0120] In some embodiments, a full core ring may be from about 120 mm to about 170 mm in length, such as 144 mm in length. In some embodiments, a mean core weight for a full core ring with 10% w / w etonogestrel may be from about 0.492 g to about 0.503 g or from about 0.480 g to about 0.520 g, such as from about 0.48 g to about 0.49 g, from about 0.48 g to about 0.50 g, from about 0.48 g to about 0.51 g, from about 0.48 g to about 0.52 g, from about 0.49 g to about 0.50 g, from about 0.49 g to about 0.51 g, from about 0.49 g to about 0.52 g, form about 0.50 g to about 0.51 g, from about 0.50 g to about 0.52 g, or from about 0.51 g to about 0.52 g, or any number therebetween.

[0121] In some embodiments, a mean core weight for a full core ring with 20% w / w etonogestrel may be from about 0.493 g to about 0.506 g or from about 0.480 g to about0.520 g, such as from about 0.48 g to about 0.49 g, from about 0.48 g to about 0.50 g, from about 0.48 g to about 0.51 g, from about 0.48 g to about 0.52 g, from about 0.49 g to about 0.50 g, from about 0.49 g to about 0.51 g, from about 0.49 g to about 0.52 g, from about 0.50 g to about 0.51 g, from about 0.50 g to about 0.52 g, or from about 0.51 g to about 0.52 g, or any number therebetween.

[0122] In some embodiments, a mean core weight for a full core ring with 15% w / w etonogestrel may be from about 0.486 g to about 0.511 g or from about 0.480 g to about 0.520 g, such as from about 0.48 g to about 0.49 g, from about 0.48 g to about 0.50 g, from about 0.48 g to about 0.51 g, from about 0.48 g to about 0.52 g, from about 0.49 g to about 0.50 g, from about 0.49 g to about 0.51 g, from about 0.49 g to about 0.52 g, from about 0.50 g to about 0.51 g, from about 0.50 g to about 0.52 g, or from about 0.51 g to about 0.52 g, or any number therebetween.

[0123] In some embodiments, the mass of a cut core, including cores cut from lengths of from about 25 mm to about 70 mm, ranges from about 89 mg to about 243 mg.

[0124] In some embodiments, the mass of the core in the vaginal system ranges from about 10 mg to about 300 mg, such as from about 10 mg to about 20 mg, from about 10 mg to about 30 mg, from about 10 mg to about 40 mg, from about 10 mg to about 50 mg, from about 10 mg to about 60 mg, from about 10 mg to about 70 mg, from about 10 mg to about 80 mg, from about 10 mg to about 90 mg, from about 10 mg to about 100 mg, from about 10 mg to about 110 mg, from about 10 mg to about 120 mg, from about 10 mg to about 130 mg, from about 10 mg to about 140 mg, from about 10 mg to about 150 mg, from about 10 mg to about 160 mg, from about 10 mg to about 170 mg, from about 10 mg to about 180 mg, from about 10 mg to about 190 mg, from about 10 mg to about 200 mg, from about 10 mg to about 210 mg, from about 10 mg to about 220 mg, from about 10 mg to about 230 mg, from about 10 mg to about 240 mg, from about 10 mg to about 250 mg, from about 10 mg to about 260 mg, from about 10 mg to about 270 mg, from about 10 mg to about 280 mg, from about 10 mg to about 290 mg, from about 20 mg to about 30 mg, from about 20 mg to about 40 mg, from about 20 mg to about 50 mg, from about 20 mg to about 60 mg, from about 20 mg to about 70 mg, from about 20 mg to about 80 mg, from about 20 mg to about 90 mg, from about 20 mg to about 100 mg, from about 20 mg to about 110 mg, from about 20 mg to about 120 mg, from about 20 mg to about 130 mg, from about 20 mg to about 140 mg, from about 20 mg to about 150 mg, from about 20 mg to about 160 mg, from about 20 mg to about 170 mg, from about 20 mg to about 180 mg, from about 20 mg to about 190 mg, from about 20 mg to about 200 mg, from about 20 mg to about 210 mg, fromabout 20 mg to about 220 mg, from about 20 mg to about 230 mg, from about 20 mg to about 240 mg, from about 20 mg to about 250 mg, from about 20 mg to about 260 mg, from about 20 mg to about 270 mg, from about 20 mg to about 280 mg, from about 20 mg to about 290 mg, from about 20 mg to about 300 mg, from about 30 mg to about 40 mg, from about 30 mg to about 50 mg, from about 30 mg to about 60 mg, from about 30 mg to about 70 mg, from about 30 mg to about 80 mg, from about 30 mg to about 90 mg, from about 30 mg to about 100 mg, from about 30 mg to about 110 mg, from about 30 mg to about 120 mg, from about 30 mg to about 130 mg, from about 30 mg to about 140 mg, from about 30 mg to about 150 mg, from about 30 mg to about 160 mg, from about 30 mg to about 170 mg, from about 30 mg to about 180 mg, from about 30 mg to about 190 mg, from about 30 mg to about 200 mg, from about 30 mg to about 210 mg, from about 30 mg to about 220 mg, from about 30 mg to about 230 mg, from about 30 mg to about 240 mg, from about 30 mg to about 250 mg, from about 30 mg to about 260 mg, from about 30 mg to about 270 mg, from about 30 mg to about 280 mg, from about 30 mg to about 290 mg, from about 30 mg to about 300 mg, from about 40 mg to about 50 mg, from about 40 mg to about 60 mg, from about 40 mg to about 70 mg, from about 40 mg to about 80 mg, from about 40 mg to about 90 mg, from about 40 mg to about 100 mg, from about 40 mg to about 110 mg, from about 40 mg to about 120 mg, from about 40 mg to about 130 mg, from about 40 mg to about 140 mg, from about 40 mg to about 150 mg, from about 40 mg to about 160 mg, from about 40 mg to about 170 mg, from about 40 mg to about 180 mg, from about 40 mg to about 190 mg, from about 40 mg to about 200 mg, from about 40 mg to about 210 mg, from about 40 mg to about 220 mg, from about 40 mg to about 230 mg, from about 40 mg to about 240 mg, from about 40 mg to about 250 mg, from about 40 mg to about 260 mg, from about 40 mg to about 270 mg, from about 40 mg to about 280 mg, from about 40 mg to about 290 mg, from about 40 mg to about 300 mg, from about 50 mg to about 60 mg, from about 50 mg to about 70 mg, from about 50 mg to about 80 mg, from about 50 mg to about 90 mg, from about 50 mg to about 100 mg, from about 50 mg to about 110 mg, from about 50 mg to about 120 mg, from about 50 mg to about 130 mg, from about 50 mg to about 140 mg, from about 50 mg to about 150 mg, from about 50 mg to about 160 mg, from about 50 mg to about 170 mg, from about 50 mg to about 180 mg, from about 50 mg to about 190 mg, from about 50 mg to about 200 mg, from about 50 mg to about 210 mg, from about 50 mg to about 220 mg, from about 50 mg to about 230 mg, from about 50 mg to about 240 mg, from about 50 mg to about 250 mg, from about 50 mg to about 260 mg, from about 50 mg to about 270 mg, from about 50 mg to about 280 mg, from about 50 mg to about 290mg, from about 50 mg to about 300 mg, from about 60 mg to about 70 mg, from about 60 mg to about 80 mg, from about 60 mg to about 90 mg, from about 60 mg to about 100 mg, from about 60 mg to about 110 mg, from about 60 mg to about 120 mg, from about 60 mg to about 130 mg, from about 60 mg to about 140 mg, from about 60 mg to about 150 mg, from about 60 mg to about 160 mg, from about 60 mg to about 170 mg, from about 60 mg to about 180 mg, from about 60 mg to about 190 mg, from about 60 mg to about 200 mg, from about 60 mg to about 210 mg, from about 60 mg to about 220 mg, from about 60 mg to about 230 mg, from about 60 mg to about 240 mg, from about 60 mg to about 250 mg, from about 60 mg to about 260 mg, from about 60 mg to about 270 mg, from about 60 mg to about 280 mg, from about 60 mg to about 290 mg, from about 60 mg to about 300 mg, from about 70 mg to about 80 mg, from about 70 mg to about 90 mg, from about 70 mg to about 100 mg, from about 70 mg to about 110 mg, from about 70 mg to about 120 mg, from about 70 mg to about 130 mg, from about 70 mg to about 140 mg, from about 70 mg to about 150 mg, from about 70 mg to about 160 mg, from about 70 mg to about 170 mg, from about 70 mg to about 180 mg, from about 70 mg to about 190 mg, from about 70 mg to about 200 mg, from about 70 mg to about 210 mg, from about 70 mg to about 220 mg, from about 70 mg to about 230 mg, from about 70 mg to about 240 mg, from about 70 mg to about 250 mg, from about 70 mg to about 260 mg, from about 70 mg to about 270 mg, from about 70 mg to about 280 mg, from about 70 mg to about 290 mg, from about 70 mg to about 300 mg, from about 80 mg to about 90 mg, from about 80 mg to about 100 mg, from about 80 mg to about 110 mg, from about 80 mg to about 120 mg, from about 80 mg to about 130 mg, from about 80 mg to about 140 mg, from about 80 mg to about 150 mg, from about 80 mg to about 160 mg, from about 80 mg to about 170 mg, from about 80 mg to about 180 mg, from about 80 mg to about 190 mg, from about 80 mg to about 200 mg, from about 80 mg to about 210 mg, from about 80 mg to about 220 mg, from about 80 mg to about 230 mg, from about 80 mg to about 240 mg, from about 80 mg to about 250 mg, from about 80 mg to about 260 mg, from about 80 mg to about 270 mg, from about 80 mg to about 280 mg, from about 80 mg to about 290 mg, from about 80 mg to about 300 mg, from about 90 mg to about 100 mg, from about 90 mg to about 110 mg, from about 90 mg to about 120 mg, from about 90 mg to about 130 mg, from about 90 mg to about 140 mg, from about 90 mg to about 150 mg, from about 90 mg to about 160 mg, from about 90 mg to about 170 mg, from about 90 mg to about 180 mg, from about 90 mg to about 190 mg, from about 90 mg to about 200 mg, from about 90 mg to about 210 mg, from about 90 mg to about 220 mg, from about 90 mg to about 230 mg, from about 90 mg to about 240 mg, fromabout 90 mg to about 250 mg, from about 90 mg to about 260 mg, from about 90 mg to about 270 mg, from about 90 mg to about 280 mg, from about 90 mg to about 290 mg, from about 90 mg to about 300 mg, from about 100 mg to about 110 mg, from about 100 mg to about 120 mg, from about 100 mg to about 130 mg, from about 100 mg to about 140 mg, from about 100 mg to about 150 mg, from about 100 mg to about 160 mg, from about 100 mg to about 170 mg, from about 100 mg to about 180 mg, from about 100 mg to about 190 mg, from about 100 mg to about 200 mg, from about 100 mg to about 210 mg, from about 100 mg to about 220 mg, from about 100 mg to about 230 mg, from about 100 mg to about 240 mg, from about 100 mg to about 250 mg, from about 100 mg to about 260 mg, from about 100 mg to about 270 mg, from about 100 mg to about 280 mg, from about 100 mg to about 290 mg, from about 100 mg to about 300 mg, from about 110 mg to about 120 mg, from about 110 mg to about 130 mg, from about 110 mg to about 140 mg, from about 110 mg to about 150 mg, from about 110 mg to about 160 mg, from about 110 mg to about 170 mg, from about 110 mg to about 180 mg, from about 110 mg to about 190 mg, from about 110 mg to about 200 mg, from about 110 mg to about 210 mg, from about 110 mg to about 220 mg, from about 110 mg to about 230 mg, from about 110 mg to about 240 mg, from about 110 mg to about 250 mg, from about 110 mg to about 260 mg, from about 110 mg to about 270 mg, from about 110 mg to about 280 mg, from about 110 mg to about 290 mg, from about 110 mg to about 300 mg, from about 120 mg to about 130 mg, from about 120 mg to about 140 mg, from about 120 mg to about 150 mg, from about 120 mg to about 160 mg, from about 120 mg to about 170 mg, from about 120 mg to about 180 mg, from about 120 mg to about 190 mg, from about 120 mg to about 200 mg, from about 120 mg to about 210 mg, from about 120 mg to about 220 mg, from about 120 mg to about 230 mg, from about 120 mg to about 240 mg, from about 120 mg to about 250 mg, from about 120 mg to about 260 mg, from about 120 mg to about 270 mg, from about 120 mg to about 280 mg, from about 120 mg to about 290 mg, from about 120 mg to about 300 mg, from about 130 mg to about 140 mg, from about 130 mg to about 150 mg, from about 130 mg to about 160 mg, from about 130 mg to about 170 mg, from about 130 mg to about 180 mg, from about 130 mg to about 190 mg, from about 130 mg to about 200 mg, from about 130 mg to about 210 mg, from about 130 mg to about 220 mg, from about 130 mg to about 230 mg, from about 130 mg to about 240 mg, from about 130 mg to about 250 mg, from about 130 mg to about 260 mg, from about 130 mg to about 270 mg, from about 130 mg to about 280 mg, from about 130 mg to about 290 mg, from about 130 mg to about 300 mg, from about 140 mg to about 150 mg, from about 140 mg to about 160 mg, from about 140 mg to about 170mg, from about 140 mg to about 180 mg, from about 140 mg to about 190 mg, from about 140 mg to about 200 mg, from about 140 mg to about 210 mg, from about 140 mg to about 220 mg, from about 140 mg to about 230 mg, from about 140 mg to about 240 mg, from about 140 mg to about 250 mg, from about 140 mg to about 260 mg, from about 140 mg to about 270 mg, from about 140 mg to about 280 mg, from about 140 mg to about 290 mg, from about 140 mg to about 300 mg, from about 150 mg to about 160 mg, from about 150 mg to about 170 mg, from about 150 mg to about 180 mg, from about 150 mg to about 190 mg, from about 150 mg to about 200 mg, from about 150 mg to about 210 mg, from about 150 mg to about 220 mg, from about 150 mg to about 230 mg, from about 150 mg to about 240 mg, from about 150 mg to about 250 mg, from about 150 mg to about 260 mg, from about 150 mg to about 270 mg, from about 150 mg to about 280 mg, from about 150 mg to about 290 mg, from about 150 mg to about 300 mg, from about 160 mg to about 170 mg, from about 160 mg to about 180 mg, from about 160 mg to about 190 mg, from about 160 mg to about 200 mg, from about 160 mg to about 210 mg, from about 160 mg to about 220 mg, from about 160 mg to about 230 mg, from about 160 mg to about 240 mg, from about 160 mg to about 250 mg, from about 160 mg to about 260 mg, from about 160 mg to about 270 mg, from about 160 mg to about 280 mg, from about 160 mg to about 290 mg, from about 160 mg to about 300 mg, from about 170 mg to about 180 mg, from about 170 mg to about 190 mg, from about 170 mg to about 200 mg, from about 170 mg to about 210 mg, from about 170 mg to about 220 mg, from about 170 mg to about 230 mg, from about 170 mg to about 240 mg, from about 170 mg to about 250 mg, from about 170 mg to about 260 mg, from about 170 mg to about 270 mg, from about 170 mg to about 280 mg, from about 170 mg to about 290 mg, from about 170 mg to about 300 mg, from about 180 mg to about 190 mg, from about 180 mg to about 200 mg, from about 180 mg to about 210 mg, from about 180 mg to about 220 mg, from about 180 mg to about 230 mg, from about 180 mg to about 240 mg, from about 180 mg to about 250 mg, from about 180 mg to about 260 mg, from about 180 mg to about 270 mg, from about 180 mg to about 280 mg, from about 180 mg to about 290 mg, from about 180 mg to about 300 mg, from about 190 mg to about 200 mg, from about 190 mg to about 210 mg, from about 190 mg to about 220 mg, from about 190 mg to about 230 mg, from about 190 mg to about 240 mg, from about 190 mg to about 250 mg, from about 190 mg to about 260 mg, from about 190 mg to about 270 mg, from about 190 mg to about 280 mg, from about 190 mg to about 290 mg, from about 190 mg to about 300 mg, from about 200 mg to about 210 mg, from about 200 mg to about 220 mg, from about 200 mg to about 230 mg, from about 200 mg to about 240 mg, from about 200mg to about 250 mg, from about 200 mg to about 260 mg, from about 200 mg to about 270 mg, from about 200 mg to about 280 mg, from about 200 mg to about 290 mg, from about 200 mg to about 300 mg, from about 210 mg to about 220 mg, from about 210 mg to about 230 mg, from about 210 mg to about 240 mg, from about 210 mg to about 250 mg, from about 210 mg to about 260 mg, from about 210 mg to about 270 mg, from about 210 mg to about 280 mg, from about 210 mg to about 290 mg, from about 210 mg to about 300 mg, from about 220 mg to about 230 mg, from about 220 mg to about 240 mg, from about 220 mg to about 250 mg, from about 220 mg to about 260 mg, from about 220 mg to about 270 mg, from about 220 mg to about 280 mg, from about 220 mg to about 290 mg, from about 220 mg to about 300 mg, from about 230 mg to about 240 mg, from about 230 mg to about 250 mg, from about 230 mg to about 260 mg, from about 230 mg to about 270 mg, from about 230 mg to about 280 mg, from about 230 mg to about 290 mg, from about 230 mg to about 300 mg, from about 240 mg to about 250 mg, from about 240 mg to about 260 mg, from about 240 mg to about 270 mg, from about 240 mg to about 280 mg, from about 240 mg to about 290 mg, from about 240 mg to about 300 mg, from about 250 mg to about 260 mg, from about 250 mg to about 270 mg, from about 250 mg to about 280 mg, from about 250 mg to about 290 mg, from about 250 mg to about 300 mg, from about 260 mg to about 270 mg, from about 260 mg to about 280 mg, from about 260 mg to about 290 mg, from about 260 mg to about 300 mg, from about 270 mg to about 280 mg, from about 270 mg to about 290 mg, from about 270 mg to about 300 mg, from about 280 mg to about 290 mg, from about 280 mg to about 300 mg, from about 290 mg to about 300 mg, or any number therebetween.

[0125] In some embodiments, the amount of progestin or the amount of etonogestrel in the core is about the same as the amount of progestin or the amount of etonogestrel in the vaginal system. In some embodiments, about less than or equal to 5 wt% of the progestin or the etonogestrel in the core can migrate to other potions of the vaginal system, including the elastomer and / or the toric body surrounding the core, such less than 5 wt% of the progestin, less than or equal to 4 wt% of the progestin, less than or equal to 3 wt% of the progestin, less than or equal to 2 wt% of the progestin, or less than or equal to 1 wt% of the progestin in the core migrating to other portions of the vaginal system.

[0126] In some embodiments, amount of the progestin in the vaginal system is from about 0.1% w / w to about 1.0% w / w of the vaginal system, such as from about 0.1% w / w to about 0.2% w / w, from about 0. 1% w / w to about 0.3% w / w, from about 0.1% w / w to about 0.4% w / w, from about 0.1% w / w to about 0.5% w / w, from about 0.1% w / w to about 0.6% w / w,from about 0.1% w / w to about 0.7% w / w, from about 0.1% w / w to about 0.8% w / w, from about 0.1% w / w to about 0.9% w / w, from about 0.2% w / w to about 0.3% w / w, from about 0.2% w / w to about 0.4% w / w, from about 0.2% w / w to about 0.5% w / w, from about 0.2% w / w to about 0.6% w / w, from about 0.2% w / w to about 0.7% w / w, from about 0.2% w / w to about 0.8% w / w, from about 0.2% w / w to about 0.9% w / w, from about 0.2% w / w to about 1.0% w / w, from about 0.3% w / w to about 0.4% w / w, from about 0.3% w / w to about 0.5% w / w, from about 0.3% w / w to about 0.6% w / w, from about 0.3% w / w to about 0.7% w / w, from about 0.3% w / w to about 0.8% w / w, from about 0.3% w / w to about 0.9% w / w, from about 0.3% w / w to about 1.0% w / w, from about 0.4% w / w to about 0.5% w / w, from about 0.4% w / w to about 0.6% w / w, from about 0.4% w / w to about 0.7% w / w, from about 0.4% w / w to about 0.8% w / w, from about 0.4% w / w to about 0.9% w / w, from about 0.4% w / w to about 1.0% w / w, from about 0.5% w / w to about 0.6% w / w, from about 0.5% w / w to about 0.7% w / w, from about 0.5% w / w to about 0.8% w / w, from about 0.5% w / w to about 0.9% w / w, from about 0.5% w / w to about 1.0% w / w, from about 0.6% w / w to about 0.7% w / w, from about 0.6% w / w to about 0.8% w / w, from about 0.6% w / w to about 0.9% w / w, from about 0.6% w / w to about 1.0% w / w, from about 0.7% w / w to about 0.8% w / w, from about 0.7% w / w to about 0.9% w / w, from about 0.7% w / w to about 1.0% w / w, from about 0.8% w / w to about 0.9% w / w, from about 0.8% w / w to about 1.0% w / w, from about 0.9% w / w to about 1.0% w / w, from about 1.0% w / w to about 1.0% w / w, or any number therebetween.

[0127] In some embodiments, the mass of progestin (such as etonogestrel) per vaginal system or per core ranges from about 10 mg to about 250 mg, such as from about 10 mg to about 20 mg, from about 10 mg to about 30 mg, from about 10 mg to about 40 mg, from about 10 mg to about 50 mg, from about 10 mg to about 60 mg, from about 10 mg to about 70 mg, from about 10 mg to about 80 mg, from about 10 mg to about 90 mg, from about 10 mg to about 100 mg, from about 10 mg to about 110 mg, from about 10 mg to about 120 mg, from about 10 mg to about 130 mg, from about 10 mg to about 140 mg, from about 10 mg to about 150 mg, from about 10 mg to about 160 mg, from about 10 mg to about 170 mg, from about 10 mg to about 180 mg, from about 10 mg to about 190 mg, from about 10 mg to about 200 mg, from about 10 mg to about 210 mg, from about 10 mg to about 220 mg, from about 10 mg to about 230 mg, from about 10 mg to about 240 mg, from about 20 mg to about 30 mg, from about 20 mg to about 40 mg, from about 20 mg to about 50 mg, from about 20 mg to about 60 mg, from about 20 mg to about 70 mg, from about 20 mg to about 80 mg, from about 20 mg to about 90 mg, from about 20 mg to about 100 mg, from about 20 mg to about 110 mg, from about 20 mg to about 120 mg, from about 20 mg toabout 130 mg, from about 20 mg to about 140 mg, from about 20 mg to about 150 mg, from about 20 mg to about 160 mg, from about 20 mg to about 170 mg, from about 20 mg to about 180 mg, from about 20 mg to about 190 mg, from about 20 mg to about 200 mg, from about 20 mg to about 210 mg, from about 20 mg to about 220 mg, from about 20 mg to about 230 mg, from about 20 mg to about 240 mg, from about 20 mg to about 250 mg, from about 30 mg to about 40 mg, from about 30 mg to about 50 mg, from about 30 mg to about 60 mg, from about 30 mg to about 70 mg, from about 30 mg to about 80 mg, from about 30 mg to about 90 mg, from about 30 mg to about 100 mg, from about 30 mg to about 110 mg, from about 30 mg to about 120 mg, from about 30 mg to about 130 mg, from about 30 mg to about 140 mg, from about 30 mg to about 150 mg, from about 30 mg to about 160 mg, from about 30 mg to about 170 mg, from about 30 mg to about 180 mg, from about 30 mg to about 190 mg, from about 30 mg to about 200 mg, from about 30 mg to about 210 mg, from about 30 mg to about 220 mg, from about 30 mg to about 230 mg, from about 30 mg to about 240 mg, from about 30 mg to about 250 mg, from about 40 mg to about 50 mg, from about 40 mg to about 60 mg, from about 40 mg to about 70 mg, from about 40 mg to about 80 mg, from about 40 mg to about 90 mg, from about 40 mg to about 100 mg, from about 40 mg to about 110 mg, from about 40 mg to about 120 mg, from about 40 mg to about 130 mg, from about 40 mg to about 140 mg, from about 40 mg to about 150 mg, from about 40 mg to about 160 mg, from about 40 mg to about 170 mg, from about 40 mg to about 180 mg, from about 40 mg to about 190 mg, from about 40 mg to about 200 mg, from about 40 mg to about 210 mg, from about 40 mg to about 220 mg, from about 40 mg to about 230 mg, from about 40 mg to about 240 mg, from about 40 mg to about 250 mg, from about 50 mg to about 60 mg, from about 50 mg to about 70 mg, from about 50 mg to about 80 mg, from about 50 mg to about 90 mg, from about 50 mg to about 100 mg, from about 50 mg to about 110 mg, from about 50 mg to about 120 mg, from about 50 mg to about 130 mg, from about 50 mg to about 140 mg, from about 50 mg to about 150 mg, from about 50 mg to about 160 mg, from about 50 mg to about 170 mg, from about 50 mg to about 180 mg, from about 50 mg to about 190 mg, from about 50 mg to about 200 mg, from about 50 mg to about 210 mg, from about 50 mg to about 220 mg, from about 50 mg to about 230 mg, from about 50 mg to about 240 mg, from about 50 mg to about 250 mg, from about 60 mg to about 70 mg, from about 60 mg to about 80 mg, from about 60 mg to about 90 mg, from about 60 mg to about 100 mg, from about 60 mg to about 110 mg, from about 60 mg to about 120 mg, from about 60 mg to about 130 mg, from about 60 mg to about 140 mg, from about 60 mg to about 150 mg, from about 60 mg to about 160 mg, from about 60 mgto about 170 mg, from about 60 mg to about 180 mg, from about 60 mg to about 190 mg, from about 60 mg to about 200 mg, from about 60 mg to about 210 mg, from about 60 mg to about 220 mg, from about 60 mg to about 230 mg, from about 60 mg to about 240 mg, from about 60 mg to about 250 mg, from about 70 mg to about 80 mg, from about 70 mg to about 90 mg, from about 70 mg to about 100 mg, from about 70 mg to about 110 mg, from about 70 mg to about 120 mg, from about 70 mg to about 130 mg, from about 70 mg to about 140 mg, from about 70 mg to about 150 mg, from about 70 mg to about 160 mg, from about 70 mg to about 170 mg, from about 70 mg to about 180 mg, from about 70 mg to about 190 mg, from about 70 mg to about 200 mg, from about 70 mg to about 210 mg, from about 70 mg to about 220 mg, from about 70 mg to about 230 mg, from about 70 mg to about 240 mg, from about 70 mg to about 250 mg, from about 80 mg to about 90 mg, from about 80 mg to about 100 mg, from about 80 mg to about 110 mg, from about 80 mg to about 120 mg, from about 80 mg to about 130 mg, from about 80 mg to about 140 mg, from about 80 mg to about 150 mg, from about 80 mg to about 160 mg, from about 80 mg to about 170 mg, from about 80 mg to about 180 mg, from about 80 mg to about 190 mg, from about 80 mg to about 200 mg, from about 80 mg to about 210 mg, from about 80 mg to about 220 mg, from about 80 mg to about 230 mg, from about 80 mg to about 240 mg, from about 80 mg to about 250 mg, from about 90 mg to about 100 mg, from about 90 mg to about 110 mg, from about 90 mg to about 120 mg, from about 90 mg to about 130 mg, from about 90 mg to about 140 mg, from about 90 mg to about 150 mg, from about 90 mg to about 160 mg, from about 90 mg to about 170 mg, from about 90 mg to about 180 mg, from about 90 mg to about 190 mg, from about 90 mg to about 200 mg, from about 90 mg to about 210 mg, from about 90 mg to about 220 mg, from about 90 mg to about 230 mg, from about 90 mg to about 240 mg, from about 90 mg to about 250 mg, from about 100 mg to about 110 mg, from about 100 mg to about 120 mg, from about 100 mg to about 130 mg, from about 100 mg to about 140 mg, from about 100 mg to about 150 mg, from about 100 mg to about 160 mg, from about 100 mg to about 170 mg, from about 100 mg to about 180 mg, from about 100 mg to about 190 mg, from about 100 mg to about 200 mg, from about 100 mg to about 210 mg, from about 100 mg to about 220 mg, from about 100 mg to about 230 mg, from about 100 mg to about 240 mg, from about 100 mg to about 250 mg, from about 110 mg to about 120 mg, from about 110 mg to about 130 mg, from about 110 mg to about 140 mg, from about 110 mg to about 150 mg, from about 110 mg to about 160 mg, from about 110 mg to about 170 mg, from about 110 mg to about 180 mg, from about 110 mg to about 190 mg, from about 110 mg to about 200 mg, from about 110 mg to about 210mg, from about 110 mg to about 220 mg, from about 110 mg to about 230 mg, from about 110 mg to about 240 mg, from about 110 mg to about 250 mg, from about 120 mg to about 130 mg, from about 120 mg to about 140 mg, from about 120 mg to about 150 mg, from about 120 mg to about 160 mg, from about 120 mg to about 170 mg, from about 120 mg to about 180 mg, from about 120 mg to about 190 mg, from about 120 mg to about 200 mg, from about 120 mg to about 210 mg, from about 120 mg to about 220 mg, from about 120 mg to about 230 mg, from about 120 mg to about 240 mg, from about 120 mg to about 250 mg, from about 130 mg to about 140 mg, from about 130 mg to about 150 mg, from about 130 mg to about 160 mg, from about 130 mg to about 170 mg, from about 130 mg to about 180 mg, from about 130 mg to about 190 mg, from about 130 mg to about 200 mg, from about 130 mg to about 210 mg, from about 130 mg to about 220 mg, from about 130 mg to about 230 mg, from about 130 mg to about 240 mg, from about 130 mg to about 250 mg, from about 140 mg to about 150 mg, from about 140 mg to about 160 mg, from about 140 mg to about 170 mg, from about 140 mg to about 180 mg, from about 140 mg to about 190 mg, from about 140 mg to about 200 mg, from about 140 mg to about 210 mg, from about 140 mg to about 220 mg, from about 140 mg to about 230 mg, from about 140 mg to about 240 mg, from about 140 mg to about 250 mg, from about 150 mg to about 160 mg, from about 150 mg to about 170 mg, from about 150 mg to about 180 mg, from about 150 mg to about 190 mg, from about 150 mg to about 200 mg, from about 150 mg to about 210 mg, from about 150 mg to about 220 mg, from about 150 mg to about 230 mg, from about 150 mg to about 240 mg, from about 150 mg to about 250 mg, from about 160 mg to about 170 mg, from about 160 mg to about 180 mg, from about 160 mg to about 190 mg, from about 160 mg to about 200 mg, from about 160 mg to about 210 mg, from about 160 mg to about 220 mg, from about 160 mg to about 230 mg, from about 160 mg to about 240 mg, from about 160 mg to about 250 mg, from about 170 mg to about 180 mg, from about 170 mg to about 190 mg, from about 170 mg to about 200 mg, from about 170 mg to about 210 mg, from about 170 mg to about 220 mg, from about 170 mg to about 230 mg, from about 170 mg to about 240 mg, from about 170 mg to about 250 mg, from about 180 mg to about 190 mg, from about 180 mg to about 200 mg, from about 180 mg to about 210 mg, from about 180 mg to about 220 mg, from about 180 mg to about 230 mg, from about 180 mg to about 240 mg, from about 180 mg to about 250 mg, from about 190 mg to about 200 mg, from about 190 mg to about 210 mg, from about 190 mg to about 220 mg, from about 190 mg to about 230 mg, from about 190 mg to about 240 mg, from about 190 mg to about 250 mg, from about 200 mg to about 210 mg, from about 200 mg to about 220 mg, from about 200mg to about 230 mg, from about 200 mg to about 240 mg, from about 200 mg to about 250 mg, from about 210 mg to about 220 mg, from about 210 mg to about 230 mg, from about 210 mg to about 240 mg, from about 210 mg to about 250 mg, from about 220 mg to about 230 mg, from about 220 mg to about 240 mg, from about 220 mg to about 250 mg, from about 230 mg to about 240 mg, from about 230 mg to about 250 mg, from about 240 mg to about 250 mg, or any number therebetween.

[0128] For the vaginal system’s release of progestin, core length and drug loading of the progestin, such as drug loading of etonogestrel, may impact the release rate of the progestin over a span of time, or such as a span of about 365 days.

[0129] In some embodiments, the core length may be about 35 mm, and the drug loading may be about 50% w / w. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 45% w / w. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 40% w / w. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 35% w / w. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 30% w / w. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 25% w / w. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 20% w / w. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 15% w / w. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 25% w / w. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 20% w / w. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 15% w / w. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 25% w / w.

[0130] In some embodiments, the core length may be about 70 mm in length or from about 25 mm to about 144 mm in length in length, such as from about 20 mm to about 30 mm, from about 20 mm to about 40 mm, from about 20 mm to about 50 mm, from about 20 mm to about 60 mm, from about 20 mm to about 70 mm, from about 20 mm to about 80 mm, from about 20 mm to about 90 mm, from about 20 mm to about 100 mm, from about 20 mm to about 110 mm, from about 20 mm to about 120 mm, from about 20 mm to about 130 mm, from about 20 mm to about 140 mm, from about 20 mm to about 150 mm, from about 30 mm to about 40 mm, from about 30 mm to about 50 mm, from about 30 mm to about 60 mm, from about 30 mm to about 70 mm, from about 30 mm to about 80 mm, from about 30 mm to about 90 mm, from about 30 mm to about 100 mm, from about 30 mm toabout 110 mm, from about 30 mm to about 120 mm, from about 30 mm to about 130 mm, from about 30 mm to about 140 mm, from about 30 mm to about 150 mm, from about 40 mm to about 50 mm, from about 40 mm to about 60 mm, from about 40 mm to about 70 mm, from about 40 mm to about 80 mm, from about 40 mm to about 90 mm, from about 40 mm to about 100 mm, from about 40 mm to about 110 mm, from about 40 mm to about 120 mm, from about 40 mm to about 130 mm, from about 40 mm to about 140 mm, from about 40 mm to about 150 mm, from about 50 mm to about 60 mm, from about 50 mm to about 70 mm, from about 50 mm to about 80 mm, from about 50 mm to about 90 mm, from about 50 mm to about 100 mm, from about 50 mm to about 110 mm, from about 50 mm to about 120 mm, from about 50 mm to about 130 mm, from about 50 mm to about 140 mm, from about 50 mm to about 150 mm, from about 60 mm to about 70 mm, from about 60 mm to about 80 mm, from about 60 mm to about 90 mm, from about 60 mm to about 100 mm, from about 60 mm to about 110 mm, from about 60 mm to about 120 mm, from about 60 mm to about 130 mm, from about 60 mm to about 140 mm, from about 60 mm to about 150 mm, from about 70 mm to about 80 mm, from about 70 mm to about 90 mm, from about 70 mm to about 100 mm, from about 70 mm to about 110 mm, from about 70 mm to about 120 mm, from about 70 mm to about 130 mm, from about 70 mm to about 140 mm, from about 70 mm to about 150 mm, from about 80 mm to about 90 mm, from about 80 mm to about 100 mm, from about 80 mm to about 110 mm, from about 80 mm to about 120 mm, from about 80 mm to about 130 mm, from about 80 mm to about 140 mm, from about 80 mm to about 150 mm, from about 90 mm to about 100 mm, from about 90 mm to about 110 mm, from about 90 mm to about 120 mm, from about 90 mm to about 130 mm, from about 90 mm to about 140 mm, from about 90 mm to about 150 mm, from about 100 mm to about 110 mm, from about 100 mm to about 120 mm, from about 100 mm to about 130 mm, from about 100 mm to about 140 mm, from about 100 mm to about 150 mm, from about 110 mm to about 120 mm, from about 110 mm to about 130 mm, from about 110 mm to about 140 mm, from about 110 mm to about 150 mm, from about 120 mm to about 130 mm, from about 120 mm to about 140 mm, from about 120 mm to about 150 mm, from about 130 mm to about 140 mm, from about 130 mm to about 150 mm, or from about 140 mm to about 150 mm, or any number therebetween. Further, the drug loading may be from about 5% w / w ETO to about 50% w / w ETO, such as an ETO loading from about 5% w / w to about 10% w / w, from about 5% w / w to about 15% w / w, from about 5% w / w to about 20% w / w, from about 5% w / w to about 25% w / w, from about 5% w / w to about 30% w / w, from about 5% w / w to about 35% w / w, from about 5% w / w to about 40% w / w, from about 5% w / w toabout 45% w / w, from about 10% w / w to about 15% w / w, from about 10% w / w to about 20% w / w, from about 10% w / w to about 25% w / w, from about 10% w / w to about 30% w / w, from about 10% w / w to about 35% w / w, from about 10% w / w to about 40% w / w, from about 10% w / w to about 45% w / w, from about 10% w / w to about 50% w / w, from about 15% w / w to about 20% w / w, from about 15% w / w to about 25% w / w, from about 15% w / w to about 30% w / w, from about 15% w / w to about 35% w / w, from about 15% w / w to about 40% w / w, from about 15% w / w to about 45% w / w, from about 15% w / w to about 50% w / w, from about 20% w / w to about 25% w / w, from about 20% w / w to about 30% w / w, from about 20% w / w to about 35% w / w, from about 20% w / w to about 40% w / w, from about 20% w / w to about 45% w / w, from about 20% w / w to about 50% w / w, from about 25% w / w to about 30% w / w, from about 25% w / w to about 35% w / w, from about 25% w / w to about 40% w / w, from about 25% w / w to about 45% w / w, from about 25% w / w to about 50% w / w, from about 30% w / w to about 35% w / w, from about 30% w / w to about 40% w / w, from about 30% w / w to about 45% w / w, from about 30% w / w to about 50% w / w, from about 35% w / w to about 40% w / w, from about 35% w / w to about 45% w / w, from about 35% w / w to about 50% w / w, from about 40% w / w to about 45% w / w, from about 40% w / w to about 50% w / w, from about 45% w / w to about 50% w / w, or any number therebetween.

[0131] In some embodiments, the core length may be about 144 mm, and the drug load may be about 10% w / w ETO. In some embodiments, the core length may be about 144 mm, and the drug load may be about 15% w / w ETO. In some embodiments, the core length may be about 144 mm, and the drug loading may be about 20% w / w ETO. In some embodiments, the core length may be about 144 mm, and the drug loading may be about 25% w / w ETO. In some embodiments, the core length may be about 144 mm, and the drug loading may be about 30% w / w ETO. In some embodiments, the core length may be about 144 mm, and the drug loading may be about 35% w / w ETO. In some embodiments, the core length may be about 144 mm, and the drug loading may be about 40% w / w ETO. In some embodiments, the core length may be about 144 mm, and the drug loading may be about 45% w / w ETO. In some embodiments, the core length may be about 144 mm, and the drug loading may be about 50% w / w ETO. In some embodiments, the core length may be about 70 mm, and the drug load may be about 10% w / w ETO. In some embodiments, the core length may be about 70 mm, and the drug load may be about 15% w / w ETO. In some embodiments, the core length may be about 70 mm, and the drug loading may be about 20% w / w ETO. In some embodiments, the core length may be about 70 mm, and thedrug loading may be about 25% w / w ETO. In some embodiments, the core length may be about 70 mm, and the drug loading may be about 30% w / w ETO. In some embodiments, the core length may be about 70 mm, and the drug loading may be about 35% w / w ETO. In some embodiments, the core length may be about 70 mm, and the drug loading may be about 40% w / w ETO. In some embodiments, the core length may be about 70 mm, and the drug loading may be about 45% w / w ETO. In some embodiments, the core length may be about 70 mm, and the drug loading may be about 50% w / w ETO. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 10% w / w ETO. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 15% w / w ETO. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 20% w / w ETO. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 25% w / w ETO. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 30% w / w ETO. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 35% w / w ETO. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 40% w / w ETO. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 45% w / w ETO. In some embodiments, the core length may be about 50 mm, and the drug loading may be about 50% w / w ETO. In some embodiments, the core length may be about 35 mm, and the drug load may be about 10% w / w ETO. In some embodiments, the core length may be about 35 mm, and the drug load may be about 15% w / w ETO. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 20% w / w ETO. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 25% w / w ETO. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 30% w / w ETO. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 35% w / w ETO. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 40% w / w ETO. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 45% w / w ETO. In some embodiments, the core length may be about 35 mm, and the drug loading may be about 50% w / w ETO. In some embodiments, the core length may be about 25 mm, and the drug load may be about 10% w / w ETO. In some embodiments, the core length may be about 25 mm, and the drug load may be about 15% w / w ETO. In some embodiments, the core length may be about 25 mm, and the drug loading may be about 20% w / w ETO. In some embodiments, the core length may be about 25 mm, and the drug loading may be about 25% w / w ETO. Insome embodiments, the core length may be about 25 mm, and the drug loading may be about 30% w / w ETO. In some embodiments, the core length may be about 25 mm, and the drug loading may be about 35% w / w ETO. In some embodiments, the core length may be about 25 mm, and the drug loading may be about 40% w / w ETO. In some embodiments, the core length may be about 25 mm, and the drug loading may be about 45% w / w ETO. In some embodiments, the core length may be about 25 mm, and the drug loading may be about 50% w / w ETO.

[0132] In some embodiments, a core diameter is fixed, such as a fixed core diameter (118), as shown in Figure 1. The fixed core diameter may be about 2.0mm. In some embodiments, the fixed core diameter (118) may be from about 0.5 mm to about 4.5 mm, or from about 0.5 mm to about 3.5 mm, such as from about 0.50 mm to about 0.75 mm, from about 0.50 mm to about 1.00 mm, from about 0.50 mm to about 1.25 mm, from about 0.50 mm to about 1.50 mm, from about 0.50 mm to about 1.75 mm, from about 0.50 mm to about 2.00 mm, from about 0.50 mm to about 2.25 mm, from about 0.50 mm to about 2.50 mm, from about 0.50 mm to about 2.75 mm, from about 0.50 mm to about 3.00 mm, from about 0.50 mm to about 3.25 mm, from about 0.50 mm to about 3.50 mm, from about 0.75 mm to about 1.00 mm, from about 0.75 mm to about 1.25 mm, from about 0.75 mm to about 1.50 mm, from about 0.75 mm to about 1.75 mm, from about 0.75 mm to about 2.00 mm, from about 0.75 mm to about 2.25 mm, from about 0.75 mm to about 2.50 mm, from about 0.75 mm to about 2.75 mm, from about 0.75 mm to about 3.00 mm, from about 0.75 mm to about 3.25 mm, from about 0.75 mm to about 3.50 mm, from about 1.00 mm to about 1.25 mm, from about 1.00 mm to about 1.50 mm, from about 1.00 mm to about 1.75 mm, from about 1.00 mm to about 2.00 mm, from about 1.00 mm to about 2.25 mm, from about 1.00 mm to about 2.50 mm, from about 1.00 mm to about 2.75 mm, from about 1.00 mm to about 3.00 mm, from about 1.00 mm to about 3.25 mm, from about 1.00 mm to about 3.50 mm, from about 1.25 mm to about 1.50 mm, from about 1.25 mm to about 1.75 mm, from about 1.25 mm to about 2.00 mm, from about 1.25 mm to about 2.25 mm, from about 1.25 mm to about 2.50 mm, from about 1.25 mm to about 2.75 mm, from about 1.25 mm to about 3.00 mm, from about 1.25 mm to about 3.25 mm, from about 1.25 mm to about 3.50 mm, from about 1.50 mm to about 1.75 mm, from about 1.50 mm to about 2.00 mm, from about 1.50 mm to about 2.25 mm, from about 1.50 mm to about 2.50 mm, from about 1.50 mm to about 2.75 mm, from about 1.50 mm to about 3.00 mm, from about 1.50 mm to about 3.25 mm, from about 1.50 mm to about 3.50 mm, from about 1.75 mm to about 2.00 mm, from about 1.75 mm to about 2.25 mm, from about 1.75 mm to about 2.50mm, from about 1.75 mm to about 2.75 mm, from about 1.75 mm to about 3.00 mm, from about 1.75 mm to about 3.25 mm, from about 1.75 mm to about 3.50 mm, from about 2.00 mm to about 2.25 mm, from about 2.00 mm to about 2.50 mm, from about 2.00 mm to about 2.75 mm, from about 2.00 mm to about 3.00 mm, from about 2.00 mm to about 3.25 mm, from about 2.00 mm to about 3.50 mm, from about 2.25 mm to about 2.50 mm, from about 2.25 mm to about 2.75 mm, from about 2.25 mm to about 3.00 mm, from about 2.25 mm to about 3.25 mm, from about 2.25 mm to about 3.50 mm, from about 2.50 mm to about 2.75 mm, from about 2.50 mm to about 3.00 mm, from about 2.50 mm to about 3.25 mm, from about 2.50 mm to about 3.50 mm, from about 2.75 mm to about 3.00 mm, from about 2.75 mm to about 3.25 mm, from about 2.75 mm to about 3.50 mm, from about 3.00 mm to about 3.25 mm, from about 3.00 mm to about 3.50 mm, or from about 3.25 mm to about 3.50 mm, any number therebetween.

[0133] In some embodiments, a ring outer diameter (114), as shown in Figure 1, is from about 55 mm to about 56 mm. In some embodiments, the ring outer diameter (114) is from about 40 mm to about 70 mm, such as from about 40 mm to about 42 mm, from about 40 mm to about 44 mm, from about 40 mm to about 46 mm, from about 40 mm to about 48 mm, from about 40 mm to about 50 mm, from about 40 mm to about 52 mm, from about 40 mm to about 54 mm, from about 40 mm to about 56 mm, from about 40 mm to about 58 mm, from about 40 mm to about 60 mm, from about 40 mm to about 62 mm, from about 40 mm to about 64 mm, from about 40 mm to about 66 mm, from about 40 mm to about 68 mm, from about 40 mm to about 70 mm, from about 42 mm to about 44 mm, from about 42 mm to about 46 mm, from about 42 mm to about 48 mm, from about 42 mm to about 50 mm, from about 42 mm to about 52 mm, from about 42 mm to about 54 mm, from about 42 mm to about 56 mm, from about 42 mm to about 58 mm, from about 42 mm to about 60 mm, from about 42 mm to about 62 mm, from about 42 mm to about 64 mm, from about 42 mm to about 66 mm, from about 42 mm to about 68 mm, from about 42 mm to about 70 mm, from about 44 mm to about 46 mm, from about 44 mm to about 48 mm, from about 44 mm to about 50 mm, from about 44 mm to about 52 mm, from about 44 mm to about 54 mm, from about 44 mm to about 56 mm, from about 44 mm to about 58 mm, from about 44 mm to about 60 mm, from about 44 mm to about 62 mm, from about 44 mm to about 64 mm, from about 44 mm to about 66 mm, from about 44 mm to about 68 mm, from about 44 mm to about 70 mm, from about 46 mm to about 48 mm, from about 46 mm to about 50 mm, from about 46 mm to about 52 mm, from about 46 mm to about 54 mm, from about 46 mm to about 56 mm, from about 46 mm to about 58 mm, from about 46 mm to about 60mm, from about 46 mm to about 62 mm, from about 46 mm to about 64 mm, from about 46 mm to about 66 mm, from about 46 mm to about 68 mm, from about 46 mm to about 70 mm, from about 48 mm to about 50 mm, from about 48 mm to about 52 mm, from about 48 mm to about 54 mm, from about 48 mm to about 56 mm, from about 48 mm to about 58 mm, from about 48 mm to about 60 mm, from about 48 mm to about 62 mm, from about 48 mm to about 64 mm, from about 48 mm to about 66 mm, from about 48 mm to about 68 mm, from about 48 mm to about 70 mm, from about 50 mm to about 52 mm, from about 50 mm to about 54 mm, from about 50 mm to about 56 mm, from about 50 mm to about 58 mm, from about 50 mm to about 60 mm, from about 50 mm to about 62 mm, from about 50 mm to about 64 mm, from about 50 mm to about 66 mm, from about 50 mm to about 68 mm, from about 50 mm to about 70 mm, from about 52 mm to about 54 mm, from about 52 mm to about 56 mm, from about 52 mm to about 58 mm, from about 52 mm to about 60 mm, from about 52 mm to about 62 mm, from about 52 mm to about 64 mm, from about 52 mm to about 66 mm, from about 52 mm to about 68 mm, from about 52 mm to about 70 mm, from about 54 mm to about 56 mm, from about 54 mm to about 58 mm, from about 54 mm to about 60 mm, from about 54 mm to about 62 mm, from about 54 mm to about 64 mm, from about 54 mm to about 66 mm, from about 54 mm to about 68 mm, from about 54 mm to about 70 mm, from about 56 mm to about 58 mm, from about 56 mm to about 60 mm, from about 56 mm to about 62 mm, from about 56 mm to about 64 mm, from about 56 mm to about 66 mm, from about 56 mm to about 68 mm, from about 56 mm to about 70 mm, from about 58 mm to about 60 mm, from about 58 mm to about 62 mm, from about 58 mm to about 64 mm, from about 58 mm to about 66 mm, from about 58 mm to about 68 mm, from about 58 mm to about 70 mm, from about 60 mm to about 62 mm, from about 60 mm to about 64 mm, from about 60 mm to about 66 mm, from about 60 mm to about 68 mm, from about 60 mm to about 70 mm, from about 62 mm to about 64 mm, from about 62 mm to about 66 mm, from about 62 mm to about 68 mm, from about 62 mm to about 70 mm, from about 64 mm to about 66 mm, from about 64 mm to about 68 mm, from about 64 mm to about 70 mm, from about 66 mm to about 68 mm, from about 66 mm to about 70 mm, or from about 68 mm to about 70 mm, or any number therebetween.

[0134] In some embodiments, a cross-sectional diameter (116) of the vaginal system (100), as shown in Figure 1, is from about 8 mm to about 9 mm. In some embodiments, the cross-sectional diameter (116) is from about 3 mm to about 14 mm, such as from about 3 mm to about 4 mm, from about 3 mm to about 5 mm, from about 3 mm to about 6 mm, from about 3 mm to about 7 mm, from about 3 mm to about 8 mm, from about 3 mm toabout 9 mm, from about 3 mm to about 10 mm, from about 3 mm to about 11 mm, from about 3 mm to about 12 mm, from about 3 mm to about 13 mm, from about 3 mm to about 14 mm, from about 4 mm to about 5 mm, from about 4 mm to about 6 mm, from about 4 mm to about 7 mm, from about 4 mm to about 8 mm, from about 4 mm to about 9 mm, from about 4 mm to about 10 mm, from about 4 mm to about 11 mm, from about 4 mm to about 12 mm, from about 4 mm to about 13 mm, from about 4 mm to about 14 mm, from about 5 mm to about 6 mm, from about 5 mm to about 7 mm, from about 5 mm to about 8 mm, from about 5 mm to about 9 mm, from about 5 mm to about 10 mm, from about 5 mm to about 11 mm, from about 5 mm to about 12 mm, from about 5 mm to about 13 mm, from about 5 mm to about 14 mm, from about 6 mm to about 7 mm, from about 6 mm to about 8 mm, from about 6 mm to about 9 mm, from about 6 mm to about 10 mm, from about 6 mm to about 11 mm, from about 6 mm to about 12 mm, from about 6 mm to about 13 mm, from about 6 mm to about 14 mm, from about 7 mm to about 8 mm, from about 7 mm to about 9 mm, from about 7 mm to about 10 mm, from about 7 mm to about 11 mm, from about 7 mm to about 12 mm, from about 7 mm to about 13 mm, from about 7 mm to about 14 mm, from about 8 mm to about 9 mm, from about 8 mm to about 10 mm, from about 8 mm to about 11 mm, from about 8 mm to about 12 mm, from about 8 mm to about 13 mm, from about 8 mm to about 14 mm, from about 9 mm to about 10 mm, from about 9 mm to about 11 mm, from about 9 mm to about 12 mm, from about 9 mm to about 13 mm, from about 9 mm to about 14 mm, from about 10 mm to about 11 mm, from about 10 mm to about 12 mm, from about 10 mm to about 13 mm, from about 10 mm to about 14 mm, from about 11 mm to about 12 mm, from about 11 mm to about 13 mm, from about 11 mm to about 14 mm, from about 12 mm to about 13 mm, from about 12 mm to about 14 mm, or from about 13 mm to about 14 mm, or any number therebetween.

[0135] In some embodiments, the core weight for a drug loaded core (104) with a drug load of about 10% w / w etonogestrel is from about 104.2 mg to about 500.0 mg or from about 0.1 mg to about 600.0 mg or from about 100 mg to about 500 mg, such as from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 100 mg to about 450 mg, from about 100 mg to about 500 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 150 mg to about 350 mg, from about 150 mg to about 400 mg, from about 150 mg to about 450 mg, from about 150 mg to about 500 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about200 mg to about 350 mg, from about 200 mg to about 400 mg, from about 200 mg to about 450 mg, from about 200 mg to about 500 mg, from about 250 mg to about 300 mg, from about 250 mg to about 350 mg, from about 250 mg to about 400 mg, from about 250 mg to about 450 mg, from about 250 mg to about 500 mg, from about 300 mg to about 350 mg, from about 300 mg to about 400 mg, from about 300 mg to about 450 mg, from about 300 mg to about 500 mg, from about 350 mg to about 400 mg, from about 350 mg to about 450 mg, from about 350 mg to about 500 mg, from about 400 mg to about 450 mg, from about 400 mg to about 500 mg, or from about 450 mg to about 500 mg, or any number therebetween.

[0136] In some embodiments, the core weight for a drug load of 15% w / w etonogestrel is from about 104.2 mg to about 500.0 mg or from about 0. 1 mg to about 600.0 mg or from about 100 mg to about 500 mg, such as from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 100 mg to about 450 mg, from about 100 mg to about 500 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 150 mg to about 350 mg, from about 150 mg to about 400 mg, from about 150 mg to about 450 mg, from about 150 mg to about 500 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, from about 200 mg to about 450 mg, from about 200 mg to about 500 mg, from about 250 mg to about 300 mg, from about 250 mg to about 350 mg, from about 250 mg to about 400 mg, from about 250 mg to about 450 mg, from about 250 mg to about 500 mg, from about 300 mg to about 350 mg, from about 300 mg to about 400 mg, from about 300 mg to about 450 mg, from about 300 mg to about 500 mg, from about 350 mg to about 400 mg, from about 350 mg to about 450 mg, from about 350 mg to about 500 mg, from about 400 mg to about 450 mg, from about 400 mg to about 500 mg, or from about 450 mg to about 500 mg, or any number therebetween.

[0137] In some embodiments, the core weight for a drug load of 20% w / w etonogestrel is from about 104.2 mg to about 500.0 mg or from about 0. 1 mg to about 600.0 mg or from about 100 mg to about 500 mg, such as from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 100 mg to about 450 mg, from about 100 mg to about 500 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg,from about 150 mg to about 350 mg, from about 150 mg to about 400 mg, from about 150 mg to about 450 mg, from about 150 mg to about 500 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, from about 200 mg to about 450 mg, from about 200 mg to about 500 mg, from about 250 mg to about 300 mg, from about 250 mg to about 350 mg, from about 250 mg to about 400 mg, from about 250 mg to about 450 mg, from about 250 mg to about 500 mg, from about 300 mg to about 350 mg, from about 300 mg to about 400 mg, from about 300 mg to about 450 mg, from about 300 mg to about 500 mg, from about 350 mg to about 400 mg, from about 350 mg to about 450 mg, from about 350 mg to about 500 mg, from about 400 mg to about 450 mg, from about 400 mg to about 500 mg, or from about 450 mg to about 500 mg, or any number therebetween.

[0138] In some embodiments, the core weight for a drug load of 25% w / w etonogestrel is from about 104.2 mg to about 500.0 mg or from about 0. 1 mg to about 600.0 mg or from about 100 mg to about 500 mg, such as from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 100 mg to about 450 mg, from about 100 mg to about 500 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 150 mg to about 350 mg, from about 150 mg to about 400 mg, from about 150 mg to about 450 mg, from about 150 mg to about 500 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, from about 200 mg to about 450 mg, from about 200 mg to about 500 mg, from about 250 mg to about 300 mg, from about 250 mg to about 350 mg, from about 250 mg to about 400 mg, from about 250 mg to about 450 mg, from about 250 mg to about 500 mg, from about 300 mg to about 350 mg, from about 300 mg to about 400 mg, from about 300 mg to about 450 mg, from about 300 mg to about 500 mg, from about 350 mg to about 400 mg, from about 350 mg to about 450 mg, from about 350 mg to about 500 mg, from about 400 mg to about 450 mg, from about 400 mg to about 500 mg, or from about 450 mg to about 500 mg, or any number therebetween.

[0139] In some embodiments, the core weight for a drug load of 30% w / w etonogestrel is from about 104.2 mg to about 500.0 mg or from about 0. 1 mg to about 600.0 mg or from about 100 mg to about 500 mg, such as from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, fromabout 100 mg to about 450 mg, from about 100 mg to about 500 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 150 mg to about 350 mg, from about 150 mg to about 400 mg, from about 150 mg to about 450 mg, from about 150 mg to about 500 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, from about 200 mg to about 450 mg, from about 200 mg to about 500 mg, from about 250 mg to about 300 mg, from about 250 mg to about 350 mg, from about 250 mg to about 400 mg, from about 250 mg to about 450 mg, from about 250 mg to about 500 mg, from about 300 mg to about 350 mg, from about 300 mg to about 400 mg, from about 300 mg to about 450 mg, from about 300 mg to about 500 mg, from about 350 mg to about 400 mg, from about 350 mg to about 450 mg, from about 350 mg to about 500 mg, from about 400 mg to about 450 mg, from about 400 mg to about 500 mg, or from about 450 mg to about 500 mg, or any number therebetween.

[0140] In some embodiments, the core weight for a drug load of 35% w / w etonogestrel is from about 104.2 mg to about 500.0 mg or from about 0. 1 mg to about 600.0 mg or from about 100 mg to about 500 mg, such as from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 100 mg to about 450 mg, from about 100 mg to about 500 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 150 mg to about 350 mg, from about 150 mg to about 400 mg, from about 150 mg to about 450 mg, from about 150 mg to about 500 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, from about 200 mg to about 450 mg, from about 200 mg to about 500 mg, from about 250 mg to about 300 mg, from about 250 mg to about 350 mg, from about 250 mg to about 400 mg, from about 250 mg to about 450 mg, from about 250 mg to about 500 mg, from about 300 mg to about 350 mg, from about 300 mg to about 400 mg, from about 300 mg to about 450 mg, from about 300 mg to about 500 mg, from about 350 mg to about 400 mg, from about 350 mg to about 450 mg, from about 350 mg to about 500 mg, from about 400 mg to about 450 mg, from about 400 mg to about 500 mg, or from about 450 mg to about 500 mg, or any number therebetween.

[0141] In some embodiments, the core weight for a drug load of 40% w / w etonogestrel is from about 104.2 mg to about 500.0 mg or from about 0. 1 mg to about 600.0 mg or from about 100 mg to about 500 mg, such as from about 100 mg to about 150 mg, from about100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 100 mg to about 450 mg, from about 100 mg to about 500 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 150 mg to about 350 mg, from about 150 mg to about 400 mg, from about 150 mg to about 450 mg, from about 150 mg to about 500 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, from about 200 mg to about 450 mg, from about 200 mg to about 500 mg, from about 250 mg to about 300 mg, from about 250 mg to about 350 mg, from about 250 mg to about 400 mg, from about 250 mg to about 450 mg, from about 250 mg to about 500 mg, from about 300 mg to about 350 mg, from about 300 mg to about 400 mg, from about 300 mg to about 450 mg, from about 300 mg to about 500 mg, from about 350 mg to about 400 mg, from about 350 mg to about 450 mg, from about 350 mg to about 500 mg, from about 400 mg to about 450 mg, from about 400 mg to about 500 mg, or from about 450 mg to about 500 mg, or any number therebetween.

[0142] In some embodiments, the core weight for a drug load of 45% w / w etonogestrel is about 145 mg, or from about 104.2 mg to about 500 mg or from about 0.1 mg to about 600.0 mg or from about 100 mg to about 500 mg, such as from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 100 mg to about 450 mg, from about 100 mg to about 500 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 150 mg to about 350 mg, from about 150 mg to about 400 mg, from about 150 mg to about 450 mg, from about 150 mg to about 500 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, from about 200 mg to about 450 mg, from about 200 mg to about 500 mg, from about 250 mg to about 300 mg, from about 250 mg to about 350 mg, from about 250 mg to about 400 mg, from about 250 mg to about 450 mg, from about 250 mg to about 500 mg, from about 300 mg to about 350 mg, from about 300 mg to about 400 mg, from about 300 mg to about 450 mg, from about 300 mg to about 500 mg, from about 350 mg to about 400 mg, from about 350 mg to about 450 mg, from about 350 mg to about 500 mg, from about 400 mg to about 450 mg, from about 400 mg to about 500 mg, or from about 450 mg to about 500 mg, or any number therebetween.

[0143] In some embodiments, the core weight for a drug load of 50% w / w etonogestrel is from about 104.2 mg to about 500.0 mg or from about 0. 1 mg to about 600.0 mg or from about 100 mg to about 500 mg, such as from about 100 mg to about 150 mg, from about 100 mg to about 200 mg, from about 100 mg to about 250 mg, from about 100 mg to about 300 mg, from about 100 mg to about 350 mg, from about 100 mg to about 400 mg, from about 100 mg to about 450 mg, from about 100 mg to about 500 mg, from about 150 mg to about 200 mg, from about 150 mg to about 250 mg, from about 150 mg to about 300 mg, from about 150 mg to about 350 mg, from about 150 mg to about 400 mg, from about 150 mg to about 450 mg, from about 150 mg to about 500 mg, from about 200 mg to about 250 mg, from about 200 mg to about 300 mg, from about 200 mg to about 350 mg, from about 200 mg to about 400 mg, from about 200 mg to about 450 mg, from about 200 mg to about 500 mg, from about 250 mg to about 300 mg, from about 250 mg to about 350 mg, from about 250 mg to about 400 mg, from about 250 mg to about 450 mg, from about 250 mg to about 500 mg, from about 300 mg to about 350 mg, from about 300 mg to about 400 mg, from about 300 mg to about 450 mg, from about 300 mg to about 500 mg, from about 350 mg to about 400 mg, from about 350 mg to about 450 mg, from about 350 mg to about 500 mg, from about 400 mg to about 450 mg, from about 400 mg to about 500 mg, or from about 450 mg to about 500 mg, or any number therebetween.

[0144] In some embodiments, the weight of ETO of the core is from about 54 mg to about 80 mg, such as from about 54 mg to about 56 mg, from about 54 mg to about 58 mg, from about 54 mg to about 60 mg, from about 54 mg to about 62 mg, from about 54 mg to about 64 mg, from about 54 mg to about 66 mg, from about 54 mg to about 68 mg, from about 54 mg to about 70 mg, from about 54 mg to about 72 mg, from about 54 mg to about 74 mg, from about 54 mg to about 76 mg, from about 54 mg to about 78 mg, from about 56 mg to about 58 mg, from about 56 mg to about 60 mg, from about 56 mg to about 62 mg, from about 56 mg to about 64 mg, from about 56 mg to about 66 mg, from about 56 mg to about 68 mg, from about 56 mg to about 70 mg, from about 56 mg to about 72 mg, from about 56 mg to about 74 mg, from about 56 mg to about 76 mg, from about 56 mg to about 78 mg, from about 56 mg to about 80 mg, from about 58 mg to about 60 mg, from about 58 mg to about 62 mg, from about 58 mg to about 64 mg, from about 58 mg to about 66 mg, from about 58 mg to about 68 mg, from about 58 mg to about 70 mg, from about 58 mg to about 72 mg, from about 58 mg to about 74 mg, from about 58 mg to about 76 mg, from about 58 mg to about 78 mg, from about 58 mg to about 80 mg, from about 60 mg to about 62 mg, from about 60 mg to about 64 mg, from about 60 mg to about 66 mg, from about 60 mg toabout 68 mg, from about 60 mg to about 70 mg, from about 60 mg to about 72 mg, from about 60 mg to about 74 mg, from about 60 mg to about 76 mg, from about 60 mg to about 78 mg, from about 60 mg to about 80 mg, from about 62 mg to about 64 mg, from about 62 mg to about 66 mg, from about 62 mg to about 68 mg, from about 62 mg to about 70 mg, from about 62 mg to about 72 mg, from about 62 mg to about 74 mg, from about 62 mg to about 76 mg, from about 62 mg to about 78 mg, from about 62 mg to about 80 mg, from about 64 mg to about 66 mg, from about 64 mg to about 68 mg, from about 64 mg to about 70 mg, from about 64 mg to about 72 mg, from about 64 mg to about 74 mg, from about 64 mg to about 76 mg, from about 64 mg to about 78 mg, from about 64 mg to about 80 mg, from about 66 mg to about 68 mg, from about 66 mg to about 70 mg, from about 66 mg to about 72 mg, from about 66 mg to about 74 mg, from about 66 mg to about 76 mg, from about 66 mg to about 78 mg, from about 66 mg to about 80 mg, from about 68 mg to about 70 mg, from about 68 mg to about 72 mg, from about 68 mg to about 74 mg, from about 68 mg to about 76 mg, from about 68 mg to about 78 mg, from about 68 mg to about 80 mg, from about 70 mg to about 72 mg, from about 70 mg to about 74 mg, from about 70 mg to about 76 mg, from about 70 mg to about 78 mg, from about 70 mg to about 80 mg, from about 72 mg to about 74 mg, from about 72 mg to about 76 mg, from about 72 mg to about 78 mg, from about 72 mg to about 80 mg, from about 74 mg to about 76 mg, from about 74 mg to about 78 mg, from about 74 mg to about 80 mg, from about 76 mg to about 78 mg, from about 76 mg to about 80 mg, from about 78 mg to about 80 mg, or any number therebetween. In some embodiments, the weight of ETO of the core is about 63 mg or about 72.5 mg.

[0145] In some embodiments, the core length for a drug load of 10% w / w etonogestrel is from about 20 mm to about 144 mm or from about 5 mm to about 200 mm or from about 20 mm to about 30 mm, from about 20 mm to about 40 mm, from about 20 mm to about 50 mm, from about 20 mm to about 60 mm, from about 20 mm to about 70 mm, from about 20 mm to about 80 mm, from about 20 mm to about 90 mm, from about 20 mm to about 100 mm, from about 20 mm to about 110 mm, from about 20 mm to about 120 mm, from about 20 mm to about 130 mm, from about 20 mm to about 140 mm, from about 20 mm to about 150 mm, from about 30 mm to about 150 mm, such as from about 30 mm to about 40 mm, from about 30 mm to about 50 mm, from about 30 mm to about 60 mm, from about 30 mm to about 70 mm, from about 30 mm to about 80 mm, from about 30 mm to about 90 mm, from about 30 mm to about 100 mm, from about 30 mm to about 110 mm, from about 30 mm to about 120 mm, from about 30 mm to about 130 mm, from about 30 mm to about 140mm, from about 30 mm to about 150 mm, from about 40 mm to about 50 mm, from about 40 mm to about 60 mm, from about 40 mm to about 70 mm, from about 40 mm to about 80 mm, from about 40 mm to about 90 mm, from about 40 mm to about 100 mm, from about 40 mm to about 110 mm, from about 40 mm to about 120 mm, from about 40 mm to about 130 mm, from about 40 mm to about 140 mm, from about 40 mm to about 150 mm, from about 50 mm to about 60 mm, from about 50 mm to about 70 mm, from about 50 mm to about 80 mm, from about 50 mm to about 90 mm, from about 50 mm to about 100 mm, from about 50 mm to about 110 mm, from about 50 mm to about 120 mm, from about 50 mm to about 130 mm, from about 50 mm to about 140 mm, from about 50 mm to about 150 mm, from about 60 mm to about 70 mm, from about 60 mm to about 80 mm, from about 60 mm to about 90 mm, from about 60 mm to about 100 mm, from about 60 mm to about 110 mm, from about 60 mm to about 120 mm, from about 60 mm to about 130 mm, from about 60 mm to about 140 mm, from about 60 mm to about 150 mm, from about 70 mm to about 80 mm, from about 70 mm to about 90 mm, from about 70 mm to about 100 mm, from about 70 mm to about 110 mm, from about 70 mm to about 120 mm, from about 70 mm to about 130 mm, from about 70 mm to about 140 mm, from about 70 mm to about 150 mm, from about 80 mm to about 90 mm, from about 80 mm to about 100 mm, from about 80 mm to about 110 mm, from about 80 mm to about 120 mm, from about 80 mm to about 130 mm, from about 80 mm to about 140 mm, from about 80 mm to about 150 mm, from about 90 mm to about 100 mm, from about 90 mm to about 110 mm, from about 90 mm to about 120 mm, from about 90 mm to about 130 mm, from about 90 mm to about 140 mm, from about 90 mm to about 150 mm, from about 100 mm to about 110 mm, from about 100 mm to about 120 mm, from about 100 mm to about 130 mm, from about 100 mm to about 140 mm, from about 100 mm to about 150 mm, from about 110 mm to about 120 mm, from about 110 mm to about 130 mm, from about 110 mm to about 140 mm, from about 110 mm to about 150 mm, from about 120 mm to about 130 mm, from about 120 mm to about 140 mm, from about 120 mm to about 150 mm, from about 130 mm to about 140 mm, from about 130 mm to about 150 mm, or from about 140 mm to about 150 mm, or any number therebetween.

[0146] In some embodiments, the core length for a drug load of 15% w / w etonogestrel is from about 20 mm to about 144 mm or from about 5 mm to about 200 mm or from about 20 mm to about 30 mm, from about 20 mm to about 40 mm, from about 20 mm to about 50 mm, from about 20 mm to about 60 mm, from about 20 mm to about 70 mm, from about 20 mm to about 80 mm, from about 20 mm to about 90 mm, from about 20 mm to about 100mm, from about 20 mm to about 110 mm, from about 20 mm to about 120 mm, from about 20 mm to about 130 mm, from about 20 mm to about 140 mm, from about 20 mm to about 150 mm, from about 30 mm to about 150 mm, such as from about 30 mm to about 40 mm, from about 30 mm to about 50 mm, from about 30 mm to about 60 mm, from about 30 mm to about 70 mm, from about 30 mm to about 80 mm, from about 30 mm to about 90 mm, from about 30 mm to about 100 mm, from about 30 mm to about 110 mm, from about 30 mm to about 120 mm, from about 30 mm to about 130 mm, from about 30 mm to about 140 mm, from about 30 mm to about 150 mm, from about 40 mm to about 50 mm, from about 40 mm to about 60 mm, from about 40 mm to about 70 mm, from about 40 mm to about 80 mm, from about 40 mm to about 90 mm, from about 40 mm to about 100 mm, from about 40 mm to about 110 mm, from about 40 mm to about 120 mm, from about 40 mm to about 130 mm, from about 40 mm to about 140 mm, from about 40 mm to about 150 mm, from about 50 mm to about 60 mm, from about 50 mm to about 70 mm, from about 50 mm to about 80 mm, from about 50 mm to about 90 mm, from about 50 mm to about 100 mm, from about 50 mm to about 110 mm, from about 50 mm to about 120 mm, from about 50 mm to about 130 mm, from about 50 mm to about 140 mm, from about 50 mm to about 150 mm, from about 60 mm to about 70 mm, from about 60 mm to about 80 mm, from about 60 mm to about 90 mm, from about 60 mm to about 100 mm, from about 60 mm to about 110 mm, from about 60 mm to about 120 mm, from about 60 mm to about 130 mm, from about 60 mm to about 140 mm, from about 60 mm to about 150 mm, from about 70 mm to about 80 mm, from about 70 mm to about 90 mm, from about 70 mm to about 100 mm, from about 70 mm to about 110 mm, from about 70 mm to about 120 mm, from about 70 mm to about 130 mm, from about 70 mm to about 140 mm, from about 70 mm to about 150 mm, from about 80 mm to about 90 mm, from about 80 mm to about 100 mm, from about 80 mm to about 110 mm, from about 80 mm to about 120 mm, from about 80 mm to about 130 mm, from about 80 mm to about 140 mm, from about 80 mm to about 150 mm, from about 90 mm to about 100 mm, from about 90 mm to about 110 mm, from about 90 mm to about 120 mm, from about 90 mm to about 130 mm, from about 90 mm to about 140 mm, from about 90 mm to about 150 mm, from about 100 mm to about 110 mm, from about 100 mm to about 120 mm, from about 100 mm to about 130 mm, from about 100 mm to about 140 mm, from about 100 mm to about 150 mm, from about 110 mm to about 120 mm, from about 110 mm to about 130 mm, from about 110 mm to about 140 mm, from about 110 mm to about 150 mm, from about 120 mm to about 130 mm, from about 120 mm to about 140 mm, from about 120 mm to about 150 mm, from about 130 mm to about 140 mm, fromabout 130 mm to about 150 mm, or from about 140 mm to about 150 mm, or any number therebetween.

[0147] In some embodiments, the core length for a drug load of 20% w / w etonogestrel is from about 20 mm to about 144 mm or from about 5 mm to about 200 mm or from about 20 mm to about 30 mm, from about 20 mm to about 40 mm, from about 20 mm to about 50 mm, from about 20 mm to about 60 mm, from about 20 mm to about 70 mm, from about 20 mm to about 80 mm, from about 20 mm to about 90 mm, from about 20 mm to about 100 mm, from about 20 mm to about 110 mm, from about 20 mm to about 120 mm, from about 20 mm to about 130 mm, from about 20 mm to about 140 mm, from about 20 mm to about 150 mm, from about 30 mm to about 150 mm, such as from about 30 mm to about 40 mm, from about 30 mm to about 50 mm, from about 30 mm to about 60 mm, from about 30 mm to about 70 mm, from about 30 mm to about 80 mm, from about 30 mm to about 90 mm, from about 30 mm to about 100 mm, from about 30 mm to about 110 mm, from about 30 mm to about 120 mm, from about 30 mm to about 130 mm, from about 30 mm to about 140 mm, from about 30 mm to about 150 mm, from about 40 mm to about 50 mm, from about 40 mm to about 60 mm, from about 40 mm to about 70 mm, from about 40 mm to about 80 mm, from about 40 mm to about 90 mm, from about 40 mm to about 100 mm, from about 40 mm to about 110 mm, from about 40 mm to about 120 mm, from about 40 mm to about 130 mm, from about 40 mm to about 140 mm, from about 40 mm to about 150 mm, from about 50 mm to about 60 mm, from about 50 mm to about 70 mm, from about 50 mm to about 80 mm, from about 50 mm to about 90 mm, from about 50 mm to about 100 mm, from about 50 mm to about 110 mm, from about 50 mm to about 120 mm, from about 50 mm to about 130 mm, from about 50 mm to about 140 mm, from about 50 mm to about 150 mm, from about 60 mm to about 70 mm, from about 60 mm to about 80 mm, from about 60 mm to about 90 mm, from about 60 mm to about 100 mm, from about 60 mm to about 110 mm, from about 60 mm to about 120 mm, from about 60 mm to about 130 mm, from about 60 mm to about 140 mm, from about 60 mm to about 150 mm, from about 70 mm to about 80 mm, from about 70 mm to about 90 mm, from about 70 mm to about 100 mm, from about 70 mm to about 110 mm, from about 70 mm to about 120 mm, from about 70 mm to about 130 mm, from about 70 mm to about 140 mm, from about 70 mm to about 150 mm, from about 80 mm to about 90 mm, from about 80 mm to about 100 mm, from about 80 mm to about 110 mm, from about 80 mm to about 120 mm, from about 80 mm to about 130 mm, from about 80 mm to about 140 mm, from about 80 mm to about 150 mm, from about 90 mm to about 100 mm, from about 90 mm to about 110 mm, from about 90 mm to about120 mm, from about 90 mm to about 130 mm, from about 90 mm to about 140 mm, from about 90 mm to about 150 mm, from about 100 mm to about 110 mm, from about 100 mm to about 120 mm, from about 100 mm to about 130 mm, from about 100 mm to about 140 mm, from about 100 mm to about 150 mm, from about 110 mm to about 120 mm, from about 110 mm to about 130 mm, from about 110 mm to about 140 mm, from about 110 mm to about 150 mm, from about 120 mm to about 130 mm, from about 120 mm to about 140 mm, from about 120 mm to about 150 mm, from about 130 mm to about 140 mm, from about 130 mm to about 150 mm, or from about 140 mm to about 150 mm, or any number therebetween.

[0148] In some embodiments, the core length for a drug load of 25% w / w etonogestrel is from about 20 mm to about 144 mm or from about 5 mm to about 200 mm or from about 20 mm to about 30 mm, from about 20 mm to about 40 mm, from about 20 mm to about 50 mm, from about 20 mm to about 60 mm, from about 20 mm to about 70 mm, from about 20 mm to about 80 mm, from about 20 mm to about 90 mm, from about 20 mm to about 100 mm, from about 20 mm to about 110 mm, from about 20 mm to about 120 mm, from about 20 mm to about 130 mm, from about 20 mm to about 140 mm, from about 20 mm to about 150 mm, from about 30 mm to about 150 mm, such as from about 30 mm to about 40 mm, from about 30 mm to about 50 mm, from about 30 mm to about 60 mm, from about 30 mm to about 70 mm, from about 30 mm to about 80 mm, from about 30 mm to about 90 mm, from about 30 mm to about 100 mm, from about 30 mm to about 110 mm, from about 30 mm to about 120 mm, from about 30 mm to about 130 mm, from about 30 mm to about 140 mm, from about 30 mm to about 150 mm, from about 40 mm to about 50 mm, from about 40 mm to about 60 mm, from about 40 mm to about 70 mm, from about 40 mm to about 80 mm, from about 40 mm to about 90 mm, from about 40 mm to about 100 mm, from about 40 mm to about 110 mm, from about 40 mm to about 120 mm, from about 40 mm to about 130 mm, from about 40 mm to about 140 mm, from about 40 mm to about 150 mm, from about 50 mm to about 60 mm, from about 50 mm to about 70 mm, from about 50 mm to about 80 mm, from about 50 mm to about 90 mm, from about 50 mm to about 100 mm, from about 50 mm to about 110 mm, from about 50 mm to about 120 mm, from about 50 mm to about 130 mm, from about 50 mm to about 140 mm, from about 50 mm to about 150 mm, from about 60 mm to about 70 mm, from about 60 mm to about 80 mm, from about 60 mm to about 90 mm, from about 60 mm to about 100 mm, from about 60 mm to about 110 mm, from about 60 mm to about 120 mm, from about 60 mm to about 130 mm, from about 60 mm to about 140 mm, from about 60 mm to about 150 mm, from about 70 mm to about80 mm, from about 70 mm to about 90 mm, from about 70 mm to about 100 mm, from about 70 mm to about 110 mm, from about 70 mm to about 120 mm, from about 70 mm to about 130 mm, from about 70 mm to about 140 mm, from about 70 mm to about 150 mm, from about 80 mm to about 90 mm, from about 80 mm to about 100 mm, from about 80 mm to about 110 mm, from about 80 mm to about 120 mm, from about 80 mm to about 130 mm, from about 80 mm to about 140 mm, from about 80 mm to about 150 mm, from about 90 mm to about 100 mm, from about 90 mm to about 110 mm, from about 90 mm to about 120 mm, from about 90 mm to about 130 mm, from about 90 mm to about 140 mm, from about 90 mm to about 150 mm, from about 100 mm to about 110 mm, from about 100 mm to about 120 mm, from about 100 mm to about 130 mm, from about 100 mm to about 140 mm, from about 100 mm to about 150 mm, from about 110 mm to about 120 mm, from about 110 mm to about 130 mm, from about 110 mm to about 140 mm, from about 110 mm to about 150 mm, from about 120 mm to about 130 mm, from about 120 mm to about 140 mm, from about 120 mm to about 150 mm, from about 130 mm to about 140 mm, from about 130 mm to about 150 mm, or from about 140 mm to about 150 mm, or any number therebetween.

[0149] In some embodiments, the core length for a drug load of 30% w / w etonogestrel is from about 20 mm to about 144 mm or from about 5 mm to about 200 mm or from about 20 mm to about 30 mm, from about 20 mm to about 40 mm, from about 20 mm to about 50 mm, from about 20 mm to about 60 mm, from about 20 mm to about 70 mm, from about 20 mm to about 80 mm, from about 20 mm to about 90 mm, from about 20 mm to about 100 mm, from about 20 mm to about 110 mm, from about 20 mm to about 120 mm, from about 20 mm to about 130 mm, from about 20 mm to about 140 mm, from about 20 mm to about 150 mm, from about 30 mm to about 150 mm, such as from about 30 mm to about 40 mm, from about 30 mm to about 50 mm, from about 30 mm to about 60 mm, from about 30 mm to about 70 mm, from about 30 mm to about 80 mm, from about 30 mm to about 90 mm, from about 30 mm to about 100 mm, from about 30 mm to about 110 mm, from about 30 mm to about 120 mm, from about 30 mm to about 130 mm, from about 30 mm to about 140 mm, from about 30 mm to about 150 mm, from about 40 mm to about 50 mm, from about 40 mm to about 60 mm, from about 40 mm to about 70 mm, from about 40 mm to about 80 mm, from about 40 mm to about 90 mm, from about 40 mm to about 100 mm, from about 40 mm to about 110 mm, from about 40 mm to about 120 mm, from about 40 mm to about 130 mm, from about 40 mm to about 140 mm, from about 40 mm to about 150 mm, from about 50 mm to about 60 mm, from about 50 mm to about 70 mm, from about 50 mm toabout 80 mm, from about 50 mm to about 90 mm, from about 50 mm to about 100 mm, from about 50 mm to about 110 mm, from about 50 mm to about 120 mm, from about 50 mm to about 130 mm, from about 50 mm to about 140 mm, from about 50 mm to about 150 mm, from about 60 mm to about 70 mm, from about 60 mm to about 80 mm, from about 60 mm to about 90 mm, from about 60 mm to about 100 mm, from about 60 mm to about 110 mm, from about 60 mm to about 120 mm, from about 60 mm to about 130 mm, from about 60 mm to about 140 mm, from about 60 mm to about 150 mm, from about 70 mm to about 80 mm, from about 70 mm to about 90 mm, from about 70 mm to about 100 mm, from about 70 mm to about 110 mm, from about 70 mm to about 120 mm, from about 70 mm to about 130 mm, from about 70 mm to about 140 mm, from about 70 mm to about 150 mm, from about 80 mm to about 90 mm, from about 80 mm to about 100 mm, from about 80 mm to about 110 mm, from about 80 mm to about 120 mm, from about 80 mm to about 130 mm, from about 80 mm to about 140 mm, from about 80 mm to about 150 mm, from about 90 mm to about 100 mm, from about 90 mm to about 110 mm, from about 90 mm to about 120 mm, from about 90 mm to about 130 mm, from about 90 mm to about 140 mm, from about 90 mm to about 150 mm, from about 100 mm to about 110 mm, from about 100 mm to about 120 mm, from about 100 mm to about 130 mm, from about 100 mm to about 140 mm, from about 100 mm to about 150 mm, from about 110 mm to about 120 mm, from about 110 mm to about 130 mm, from about 110 mm to about 140 mm, from about 110 mm to about 150 mm, from about 120 mm to about 130 mm, from about 120 mm to about 140 mm, from about 120 mm to about 150 mm, from about 130 mm to about 140 mm, from about 130 mm to about 150 mm, or from about 140 mm to about 150 mm, or any number therebetween.

[0150] In some embodiments, the core length for a drug load of 35% w / w etonogestrel is from about 20 mm to about 144 mm or from about 5 mm to about 200 mm or from about 20 mm to about 30 mm, from about 20 mm to about 40 mm, from about 20 mm to about 50 mm, from about 20 mm to about 60 mm, from about 20 mm to about 70 mm, from about 20 mm to about 80 mm, from about 20 mm to about 90 mm, from about 20 mm to about 100 mm, from about 20 mm to about 110 mm, from about 20 mm to about 120 mm, from about 20 mm to about 130 mm, from about 20 mm to about 140 mm, from about 20 mm to about 150 mm, from about 30 mm to about 150 mm, such as from about 30 mm to about 40 mm, from about 30 mm to about 50 mm, from about 30 mm to about 60 mm, from about 30 mm to about 70 mm, from about 30 mm to about 80 mm, from about 30 mm to about 90 mm, from about 30 mm to about 100 mm, from about 30 mm to about 110 mm, from about 30mm to about 120 mm, from about 30 mm to about 130 mm, from about 30 mm to about 140 mm, from about 30 mm to about 150 mm, from about 40 mm to about 50 mm, from about 40 mm to about 60 mm, from about 40 mm to about 70 mm, from about 40 mm to about 80 mm, from about 40 mm to about 90 mm, from about 40 mm to about 100 mm, from about 40 mm to about 110 mm, from about 40 mm to about 120 mm, from about 40 mm to about 130 mm, from about 40 mm to about 140 mm, from about 40 mm to about 150 mm, from about 50 mm to about 60 mm, from about 50 mm to about 70 mm, from about 50 mm to about 80 mm, from about 50 mm to about 90 mm, from about 50 mm to about 100 mm, from about 50 mm to about 110 mm, from about 50 mm to about 120 mm, from about 50 mm to about 130 mm, from about 50 mm to about 140 mm, from about 50 mm to about 150 mm, from about 60 mm to about 70 mm, from about 60 mm to about 80 mm, from about 60 mm to about 90 mm, from about 60 mm to about 100 mm, from about 60 mm to about 110 mm, from about 60 mm to about 120 mm, from about 60 mm to about 130 mm, from about 60 mm to about 140 mm, from about 60 mm to about 150 mm, from about 70 mm to about 80 mm, from about 70 mm to about 90 mm, from about 70 mm to about 100 mm, from about 70 mm to about 110 mm, from about 70 mm to about 120 mm, from about 70 mm to about 130 mm, from about 70 mm to about 140 mm, from about 70 mm to about 150 mm, from about 80 mm to about 90 mm, from about 80 mm to about 100 mm, from about 80 mm to about 110 mm, from about 80 mm to about 120 mm, from about 80 mm to about 130 mm, from about 80 mm to about 140 mm, from about 80 mm to about 150 mm, from about 90 mm to about 100 mm, from about 90 mm to about 110 mm, from about 90 mm to about 120 mm, from about 90 mm to about 130 mm, from about 90 mm to about 140 mm, from about 90 mm to about 150 mm, from about 100 mm to about 110 mm, from about 100 mm to about 120 mm, from about 100 mm to about 130 mm, from about 100 mm to about 140 mm, from about 100 mm to about 150 mm, from about 110 mm to about 120 mm, from about 110 mm to about 130 mm, from about 110 mm to about 140 mm, from about 110 mm to about 150 mm, from about 120 mm to about 130 mm, from about 120 mm to about 140 mm, from about 120 mm to about 150 mm, from about 130 mm to about 140 mm, from about 130 mm to about 150 mm, or from about 140 mm to about 150 mm, or any number therebetween.

[0151] In some embodiments, the core length for a drug load of 40% w / w etonogestrel is from about 20 mm to about 144 mm or from about 5 mm to about 200 mm or from about 20 mm to about 30 mm, from about 20 mm to about 40 mm, from about 20 mm to about 50 mm, from about 20 mm to about 60 mm, from about 20 mm to about 70 mm, from about 20mm to about 80 mm, from about 20 mm to about 90 mm, from about 20 mm to about 100 mm, from about 20 mm to about 110 mm, from about 20 mm to about 120 mm, from about 20 mm to about 130 mm, from about 20 mm to about 140 mm, from about 20 mm to about 150 mm, from about 30 mm to about 150 mm, such as from about 30 mm to about 40 mm, from about 30 mm to about 50 mm, from about 30 mm to about 60 mm, from about 30 mm to about 70 mm, from about 30 mm to about 80 mm, from about 30 mm to about 90 mm, from about 30 mm to about 100 mm, from about 30 mm to about 110 mm, from about 30 mm to about 120 mm, from about 30 mm to about 130 mm, from about 30 mm to about 140 mm, from about 30 mm to about 150 mm, from about 40 mm to about 50 mm, from about 40 mm to about 60 mm, from about 40 mm to about 70 mm, from about 40 mm to about 80 mm, from about 40 mm to about 90 mm, from about 40 mm to about 100 mm, from about 40 mm to about 110 mm, from about 40 mm to about 120 mm, from about 40 mm to about 130 mm, from about 40 mm to about 140 mm, from about 40 mm to about 150 mm, from about 50 mm to about 60 mm, from about 50 mm to about 70 mm, from about 50 mm to about 80 mm, from about 50 mm to about 90 mm, from about 50 mm to about 100 mm, from about 50 mm to about 110 mm, from about 50 mm to about 120 mm, from about 50 mm to about 130 mm, from about 50 mm to about 140 mm, from about 50 mm to about 150 mm, from about 60 mm to about 70 mm, from about 60 mm to about 80 mm, from about 60 mm to about 90 mm, from about 60 mm to about 100 mm, from about 60 mm to about 110 mm, from about 60 mm to about 120 mm, from about 60 mm to about 130 mm, from about 60 mm to about 140 mm, from about 60 mm to about 150 mm, from about 70 mm to about 80 mm, from about 70 mm to about 90 mm, from about 70 mm to about 100 mm, from about 70 mm to about 110 mm, from about 70 mm to about 120 mm, from about 70 mm to about 130 mm, from about 70 mm to about 140 mm, from about 70 mm to about 150 mm, from about 80 mm to about 90 mm, from about 80 mm to about 100 mm, from about 80 mm to about 110 mm, from about 80 mm to about 120 mm, from about 80 mm to about 130 mm, from about 80 mm to about 140 mm, from about 80 mm to about 150 mm, from about 90 mm to about 100 mm, from about 90 mm to about 110 mm, from about 90 mm to about 120 mm, from about 90 mm to about 130 mm, from about 90 mm to about 140 mm, from about 90 mm to about 150 mm, from about 100 mm to about 110 mm, from about 100 mm to about 120 mm, from about 100 mm to about 130 mm, from about 100 mm to about 140 mm, from about 100 mm to about 150 mm, from about 110 mm to about 120 mm, from about 110 mm to about 130 mm, from about 110 mm to about 140 mm, from about 110 mm to about 150 mm, from about 120 mm to about 130 mm, from about 120 mm to about 140mm, from about 120 mm to about 150 mm, from about 130 mm to about 140 mm, from about 130 mm to about 150 mm, or from about 140 mm to about 150 mm, or any number therebetween.

[0152] In some embodiments, the core length for a drug load of 45% w / w etonogestrel is from about 20 mm to about 144 mm or from about 5 mm to about 200 mm or from about 20 mm to about 30 mm, from about 20 mm to about 40 mm, from about 20 mm to about 50 mm, from about 20 mm to about 60 mm, from about 20 mm to about 70 mm, from about 20 mm to about 80 mm, from about 20 mm to about 90 mm, from about 20 mm to about 100 mm, from about 20 mm to about 110 mm, from about 20 mm to about 120 mm, from about 20 mm to about 130 mm, from about 20 mm to about 140 mm, from about 20 mm to about 150 mm, from about 30 mm to about 150 mm, such as from about 30 mm to about 40 mm, from about 30 mm to about 50 mm, from about 30 mm to about 60 mm, from about 30 mm to about 70 mm, from about 30 mm to about 80 mm, from about 30 mm to about 90 mm, from about 30 mm to about 100 mm, from about 30 mm to about 110 mm, from about 30 mm to about 120 mm, from about 30 mm to about 130 mm, from about 30 mm to about 140 mm, from about 30 mm to about 150 mm, from about 40 mm to about 50 mm, from about 40 mm to about 60 mm, from about 40 mm to about 70 mm, from about 40 mm to about 80 mm, from about 40 mm to about 90 mm, from about 40 mm to about 100 mm, from about 40 mm to about 110 mm, from about 40 mm to about 120 mm, from about 40 mm to about 130 mm, from about 40 mm to about 140 mm, from about 40 mm to about 150 mm, from about 50 mm to about 60 mm, from about 50 mm to about 70 mm, from about 50 mm to about 80 mm, from about 50 mm to about 90 mm, from about 50 mm to about 100 mm, from about 50 mm to about 110 mm, from about 50 mm to about 120 mm, from about 50 mm to about 130 mm, from about 50 mm to about 140 mm, from about 50 mm to about 150 mm, from about 60 mm to about 70 mm, from about 60 mm to about 80 mm, from about 60 mm to about 90 mm, from about 60 mm to about 100 mm, from about 60 mm to about 110 mm, from about 60 mm to about 120 mm, from about 60 mm to about 130 mm, from about 60 mm to about 140 mm, from about 60 mm to about 150 mm, from about 70 mm to about 80 mm, from about 70 mm to about 90 mm, from about 70 mm to about 100 mm, from about 70 mm to about 110 mm, from about 70 mm to about 120 mm, from about 70 mm to about 130 mm, from about 70 mm to about 140 mm, from about 70 mm to about 150 mm, from about 80 mm to about 90 mm, from about 80 mm to about 100 mm, from about 80 mm to about 110 mm, from about 80 mm to about 120 mm, from about 80 mm to about 130 mm, from about 80 mm to about 140 mm, from about 80 mm to about 150 mm, from about90 mm to about 100 mm, from about 90 mm to about 110 mm, from about 90 mm to about 120 mm, from about 90 mm to about 130 mm, from about 90 mm to about 140 mm, from about 90 mm to about 150 mm, from about 100 mm to about 110 mm, from about 100 mm to about 120 mm, from about 100 mm to about 130 mm, from about 100 mm to about 140 mm, from about 100 mm to about 150 mm, from about 110 mm to about 120 mm, from about 110 mm to about 130 mm, from about 110 mm to about 140 mm, from about 110 mm to about 150 mm, from about 120 mm to about 130 mm, from about 120 mm to about 140 mm, from about 120 mm to about 150 mm, from about 130 mm to about 140 mm, from about 130 mm to about 150 mm, or from about 140 mm to about 150 mm, or any number therebetween.

[0153] In some embodiments, the core length for a drug load of 50% w / w etonogestrel is from about 20 mm to about 144 mm or from about 5 mm to about 200 mm or from about 20 mm to about 30 mm, from about 20 mm to about 40 mm, from about 20 mm to about 50 mm, from about 20 mm to about 60 mm, from about 20 mm to about 70 mm, from about 20 mm to about 80 mm, from about 20 mm to about 90 mm, from about 20 mm to about 100 mm, from about 20 mm to about 110 mm, from about 20 mm to about 120 mm, from about 20 mm to about 130 mm, from about 20 mm to about 140 mm, from about 20 mm to about 150 mm, from about 30 mm to about 150 mm, such as from about 30 mm to about 40 mm, from about 30 mm to about 50 mm, from about 30 mm to about 60 mm, from about 30 mm to about 70 mm, from about 30 mm to about 80 mm, from about 30 mm to about 90 mm, from about 30 mm to about 100 mm, from about 30 mm to about 110 mm, from about 30 mm to about 120 mm, from about 30 mm to about 130 mm, from about 30 mm to about 140 mm, from about 30 mm to about 150 mm, from about 40 mm to about 50 mm, from about 40 mm to about 60 mm, from about 40 mm to about 70 mm, from about 40 mm to about 80 mm, from about 40 mm to about 90 mm, from about 40 mm to about 100 mm, from about 40 mm to about 110 mm, from about 40 mm to about 120 mm, from about 40 mm to about 130 mm, from about 40 mm to about 140 mm, from about 40 mm to about 150 mm, from about 50 mm to about 60 mm, from about 50 mm to about 70 mm, from about 50 mm to about 80 mm, from about 50 mm to about 90 mm, from about 50 mm to about 100 mm, from about 50 mm to about 110 mm, from about 50 mm to about 120 mm, from about 50 mm to about 130 mm, from about 50 mm to about 140 mm, from about 50 mm to about 150 mm, from about 60 mm to about 70 mm, from about 60 mm to about 80 mm, from about 60 mm to about 90 mm, from about 60 mm to about 100 mm, from about 60 mm to about 110 mm, from about 60 mm to about 120 mm, from about 60 mm to about 130 mm, from about60 mm to about 140 mm, from about 60 mm to about 150 mm, from about 70 mm to about 80 mm, from about 70 mm to about 90 mm, from about 70 mm to about 100 mm, from about 70 mm to about 110 mm, from about 70 mm to about 120 mm, from about 70 mm to about 130 mm, from about 70 mm to about 140 mm, from about 70 mm to about 150 mm, from about 80 mm to about 90 mm, from about 80 mm to about 100 mm, from about 80 mm to about 110 mm, from about 80 mm to about 120 mm, from about 80 mm to about 130 mm, from about 80 mm to about 140 mm, from about 80 mm to about 150 mm, from about 90 mm to about 100 mm, from about 90 mm to about 110 mm, from about 90 mm to about 120 mm, from about 90 mm to about 130 mm, from about 90 mm to about 140 mm, from about 90 mm to about 150 mm, from about 100 mm to about 110 mm, from about 100 mm to about 120 mm, from about 100 mm to about 130 mm, from about 100 mm to about 140 mm, from about 100 mm to about 150 mm, from about 110 mm to about 120 mm, from about 110 mm to about 130 mm, from about 110 mm to about 140 mm, from about 110 mm to about 150 mm, from about 120 mm to about 130 mm, from about 120 mm to about 140 mm, from about 120 mm to about 150 mm, from about 130 mm to about 140 mm, from about 130 mm to about 150 mm, or from about 140 mm to about 150 mm, or any number therebetween.

[0154] In preferred embodiments, the core length for a drug loaded core (104) with drug load of 45% w / w etonogestrel is from about 30 mm to about 40 mm, such as about 35 mm, such that the release is from about 10 pg / day to about 70 pg / day, or from about 30 pg / day to about 50 pg / day, or from about 40 pg / day to about 50 pg / day, or from about 43 pg / day to about 47 pg / day, or about 45 pg / day.

[0155] In preferred embodiments, the release of etonogestrel during the steady state release period results in a blood level of the female of equal to or greater than about 140 pg / mL.

[0156] In an embodiment, the daily amount of progestin released stays substantially similar throughout the use cycle of the vaginal system (100). In an embodiment, the daily amount of progestin released varies slightly throughout the use cycle of the vaginal system (100). In an embodiment, the daily amount of progestin released varies substantially throughout the use cycle of the vaginal system (100). In an embodiment, the daily amount of progestin released varies based on the length of time that the vaginal system (100) is inserted.

[0157] The initial insertion of the vaginal system (100) can be performed by the female (300) in need thereof without the assistance of a medical professional. The vaginal system(100) can be inserted using a variety of techniques. The female (300) in need thereof can choose an insertion position that is comfortable, such as lying down, squatting, or standing. In an embodiment, the sides of the vaginal system (100) can be pressed together for the insertion into the vagina. In an embodiment, the vaginal system (100) may be inserted by using a tampon-like delivery system in order to place the vaginal system (100) in the vagina (302) of a female (300) in need thereof. When properly inserted, the vaginal system (100) should be entirely in the vagina (302) and behind the pelvic bone.

[0158] The vaginal system (100) can be removed, for example, by hooking an index finger into the vaginal system (100) inside the vagina (302) and gently pulling the vaginal system (100).

[0159] In an embodiment, any available vaginal system (100) with such capability can be used in accordance with the present invention, including those that are manufactured using extrusion technology. In an embodiment, a method of making the vaginal system (100) described herein comprises inserting at least one drug loaded core (104) into a solid mold; and injecting the polymeric material around the at least one drug loaded core (104) to form the vaginal system (100), such as injecting the polymeric material around the at least one drug loaded core (104) to form the vaginal system (100) at a temperature equal to or less than about 100°C.Examples

[0160] Specific embodiments will now be demonstrated by reference to the following examples. It should be understood that these examples are disclosed solely by way of illustrating the invention and should not be taken in any way to limit the scope of the present invention. It should be noted that the tables are presented for illustrative purposes only.

[0161] Examples herein include results for gaining a preferred daily release stably around 40 pg / day over a long period, such as a year. As shown in Figure 9, embodiments of the present disclosure have shown more steady shelf life than that of currently marketed products such as the NuvaRing.

[0162] Manufacturing process involved preparation of Elastomer Mix, Active Mix Manufacture, Core manufacture, Half and Full Ring Manufacture known as encapsulation. Elastomer Mix was prepared by mixing cured dimethyl polysiloxane silanol, silica, normal propyl orthosilicate, stannous octoate; and etonogestrel in a Dual Asymmetric Centrifugal(DAC) Mixer (Speed Mixer). Active Mix manufacture was completed either by using Dual Asymmetric Centrifugal (DAC) Mixer (Speed Mixer) or Z blade Mixer. The Active Mix was used to prepare core manufacture. These cores were manufactured either by an injection molding system or a core extrusion process. Once these cores were manufactured and cured, there were cut into the specific lengths and then encapsulated using Elastomer Mix to form the half and full ring manufacture. A flow chart of manufacturing process is shown in Figure 23.

[0163] Elastomer Mix was prepared by mixing dimethyl polysiloxane silanol, silica, and normal propyl orthosilicate, in a Planetary Mixer or using the mixing cup in a Dual Asymmetric Centrifugal Mixer (Speed mixer) and mixing with either defined speed and time or varying speed and time to form a uniform Elastomer Mix.

[0164] In one example using a DAC mixer, 10% w / w to 50% w / w Etonogestrel Active Mix was prepared by mixing etonogestrel and Elastomer Mix with or without barium sulfate into the speed mixer with varying speed and time to form the uniform Active Mix.

[0165] In another example using a Z Blade mixer, 10% w / w to 50% w / w Etonogestrel Active Mix was prepared by mixing etonogestrel, , Elastomer Mix, and a filler composition into the speed mixer with varying speed and time to form the uniform Active Mix.

[0166] In one example using injection molding, Active Mix was stored to -20°C or at room temperature or any temperature in between. Active Mix was catalyzed with the catalyst (e.g., Stannous Octoate) in the varying ratio of 100: 1 to 500: 1 or any ratio in between. Once the catalyst (e.g., Stannous Octoate) was mixed with Active Mix, it was injected into the predesigned core ring mold and heated to elevated temperature to cure the core ring. Once the core was fully cured it was detabbed and cut into certain length to form a drug loaded core.

[0167] In another example using an extruder, Active Mix was stored to -20°C or at room temperature or any temperature in between. This Active Mix was catalyzed with the catalyst (e.g., Stannous Octoate) in the varying ratio of 100: 1 to 500: 1 or any ratio in between. This Active Mix was then passed into the extruder containing 1.9 mm to 2.1 mm die to form a 2 mm core diameter. These extruded cores were dried at elevated temperature and then spooled on to the reel. Once the core was fully cured it was cut into different lengths.

[0168] Drug loaded cores manufactured were then put into the half ring mold. Elastomer Mix containing catalyst (e.g., Stannous Octoate) was injected into the half ring mold. These molds were heated to elevated temperature for a varying time to cure the half ring. These half rings were further flipped into the heated full ring mold and injected with ElastomerMix containing catalyst (e.g., Stannous Octoate) for varying time to form a full ring of the vaginal system.

[0169] As shown in Figure 3, it was shown that the longer the core length, the greater the etonogestrel release because the core length is directly proportional to the amount of etonogestrel. Exemplary embodiments were tested, as shown in Figure 3, showing the aforementioned trend of mean release of progestin in relation to time for various core lengths and ETO loads. Moreover, to hit a target ETO release of 40-45 pg / day, cores of 35 mm provided desired results.

[0170] As shown in Figures 4A-4C, core lengths of 35 mm provided desired results for hitting a target ETO release of 40-45 pg / day, whereas cores with lesser core lengths had mean ETO releases lower than a target ETO release of 40-45 pg / day. On the other hand, cores with very high core lengths, such as 70 mm (i.e., Figure 4A) resulted in mean releases much higher than the target ETO release of 40-45 pg / day.

[0171] In Figures 5A-5C, a higher drug loading of ETO correlated with a higher ETO release per day and, notably, at a 35 mm core length, a 15% w / w ETO core did not produce an ETO release sufficiently close to a target ETO release of 40-45 pg / day (i.e., see Figure 5A). Notably, a 50 mm core of about 20% w / w produced an ETO release near a target ETO release of 40-45 pg / day for a substantial number of days out of a 500-day period (i.e., see Figure 5B), and a core of about 45% w / w at 35 mm produced an ETO release near the target ETO release of 40-45 pg / day for a substantial number of days out of a 500-day period (i.e., see Figure 5C).

[0172] As seen in Figure 8A, it has been found that the initial burst release increases with greater core length. Further, when comparing Figure 8A results to those of Figures 8B to 8C, the different core lengths had a greater effect on the burst release than the drug loading of ETO.

[0173] An exemplary appearance of the vaginal system is described below in Table 1.

[0174] Table 1: Exemplary Appearance and Dimensions for Vaginal System

[0175] Notably, an exemplary embodiment with about 35 mm core length, and an etonogestrel loading of about 20% w / w-45% w / w, provided stable release rates near 40 pg or 45 pg, as can be seen in Figures 6A and 6B, where the 35 mm core having 20% w / w ETO or 45% w / w ETO maintained an ETO release of about 40-45 pg / day for about 3-5 months shortly after use.

[0176] Figures 7A-7C further supports that a core length of 35 mm provided desirable release rates near a target ETO release of 40-45 pg / day, as every example thereof with a mean ETO release of 40-45 pg / day included a vaginal ring with a 35 mm core length.

[0177] On the other hand, Figure 7D shows that cores longer than 35 mm, such as cores of length 50 mm, met a target ETO release of 40-45 pg / day with lower drug loadings, such as 15% w / w ETO or 10% w / w ETO.

[0178] Figure 11 shows core weight for different cores having different drug loading. Further, Figure 12 provides a more detailed analysis of core weight results, insofar as it also includes the variable of core length. Similarly, the core weight of a full ring is also shown in Figure 13.

[0179] Below are dissolution results (for etonogestrel released in pg / day) for various exemplary embodiments (of differing length in mm and etonogestrel manufactured core concentrations in % w / w) for various days from experiments in vaginal system manufacture, wherein release of etonogestrel only fluctuated within a range of less than or equal to 20. Opg, 19.5pg, 19.0pg, 18.5pg, 18.0pg, 17.5pg, 17.0pg, 16.5pg, 16.0pg, 15.5pg, 15.0pg, 14.5pg, 14. Opg, 13.5pg, 13. Opg, 12.5pg, 12. Opg, 11.5pg, 11. Opg, 10.5pg, or 10. Opg over a 200-day period immediately after release has stabilized and / or immediately after the initial release period in some embodiments, or wherein the day-by-day etonogestrel release (such as the release of etonogestrel on one day and then the release of etonogestrel on the next consecutive day after the one day) only changed within a range of less than or equal to 4. Opg, 4.5pg, 5. Opg, 5.5pg, 6. Opg, 6.5pg, 7. Opg, 7.5pg 8. Opg, 8.5pg, 9. Opg, 9.5pg, or 10. Opg for the first 200 days immediately after release has stabilized and / or immediately after the initial release period in some embodiments.

[0180] As seen in Figures 9 and 10, the shelflife of embodiments of this disclosure shows fairly stable results for embodiments with an etonogestrel load of 10% w / w, 15% w / w, or 20% w / w and a core length of 35 mm or 50 mm. Notably, an etonogestrel load of 15% w / w and 35 mm provided stable release from about 30 pg to about 45 pg over a 300-day period.

[0181] Figures 14-20 show cumulative release data for various embodiments over various tests leading to results. As can be seen in Figure 14, the greater the core length is, the higher cumulative release accrued over time (i.e., comparing an embodiment having about 25 mm and 15% w / w etonogestrel versus an embodiment having about 70 mm and 15% w / w etonogestrel). Figure 20 showed similar results to Figure 14, wherein halving the core length showed a decrease in the cumulative release over time. Figure 19 shows cumulative release of etonogestrel vs. drug remaining in an embodiment, and notably the trend is quite linear. Figure 15 provides results showing that the etonogestrel loading did not have as significant effects on cumulative release as core length, as the cumulative releases were very similar across the embodiments. Figure 16 shows similar results as Figure 15, although, notably, over time, an embodiment with 20% w / w load did slightly rise noticeably ahead of embodiments with 15% w / w and 10% w / w load. Likewise, in Figure 17, cumulative release across embodiments with the same, or about the same, lengths but with different drug loads showed similar cumulative release results, although the % drug remaining appeared to remain higher for embodiments with higher drug loading as time passed. A similar showing of results is found in Figure 18, where the cumulative release data is similar across embodiments with different drug loads, but the % drug remaining was less for embodiments with lower drug loads than embodiments with higher drug loads as time passed.

[0182] Figures 4A-4C and 5A-5C show various exemplary embodiments having different dissolution results based on changing the drug load and core length for embodiments with drug loads of about 10% w / w, about 15% w / w, about 20% w / w, or about 45% w / w and with core lengths of about 25 mm, about 30 mm, about 35 mm, about 50 mm, or about 70 mm. Further, Figures 8A-8C show burst releases of exemplary embodiments with about 10% w / w, about 15% w / w, about 20% w / w, about 45% w / w and with core lengths of about 25 mm, about 30 mm, about 35 mm, about 50 mm, or about 70 mm. Generally, a preferrable mean release was from about 40 pg / day to about 45 pg / day. Tables 2-20 are provided below conveying results of exemplary embodiments with about 10% w / w, about 15% w / w, or about 20% w / w and with core lengths of about 25 mm, about 30 mm, about 35 mm, about 50 mm, or about 70 mm.

[0183] Table 2: Example Ring Embodiments, Dimensions and Drug Load

[0184] Table 3: Example Ring Embodiments, Mass

[0185] Table 4: Example Rings’ ETO Release Data at 0, 12, 20, 24, and 36 Weeks

[0186] Table 5: Burst ETO Release and Mean ETO Release After 91, 180, and 364Days for Examples 1-14

[0187] Table 6: Mean ETO Release After 28, 63, 91, 147, 177, 211, 238, 266, 295, 323,343, 364, 399, 448, and 469 Days

[0188] Table 7: Release Data for Core of Length 35 mm & ETO Load of 15% w / w for Example 1 (3 samples of the core used)

[0189] Table 8: Release Data for Core of Length 50 mm & ETO Load of 15% w / w for Example 2

[0190] Table 9: Release Data for Core of Length 50 mm & ETO Load of 10% w / w for Example 3

[0191] Table 10: Release Data for Core of Length 50 mm & ETO Load of 20% w / w for Example 4

[0192] Table 11: Release Data for Core of Length 35 mm & ETO Load of 15% w / w for Example 5 (6 samples of the core used)

[0193] Table 12: Release Data for Core of Length 70 mm & ETO Load of 15% w / w for Example 6

[0194] Table 13: Release Data for Core of Length 25 mm & ETO Load of 15% w / w for Example 7

[0195] Table 14: Release Data for Core of Length 30 mm & ETO Load of 15% w / w for Example 8

[0196] Table 15: Release Data for Core of Length 35 mm & ETO Load of 20% w / w for Example 9

[0197] Table 16: Release Data for Core of Length 25 mm & ETO Load of 20% w / w for Example 10

[0198] Table 17: Release Data for Core of Length 30 mm & ETO Load of 20% w / w for Example 11

[0199] Table 18: Release Data for Core of Length 35 mm & ETO Load of 20% w / w for Example 12

[0200] Table 19: Release Data for Core of Length 35 mm & ETO Load of 20% w / w for Example 1335 mm & 20% w / w

[0201] Table 20: Release Data for Core of Length 35 mm & ETO Load of 45% w / w for Example 14

[0202] Exemplary embodiments with a core length of 35 mm for vaginal systems with 15% w / w etonogestrel produced promising results of about a 40 pg / day etonogestrel release target. The exemplary embodiments found in the tables above are meant to aid in an understanding of the invention disclosed in the present application and are not limiting to embodiments of the present application.

[0203] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. It will be further understood that terms used herein should be interpreted as having a meaning consistent with their meaning in the context of this specification and the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

[0204] It is to be understood that the present disclosure is not limited to the aspects described above and illustrated in the drawings; rather, the skilled person will recognize that many changes and modifications may be made within the scope of the present disclosure and appended claims. In the drawings and specification, there have been disclosed aspectsfor purposes of illustration only and not for purposes of limitation, the scope of the inventive concepts being set forth in the following claims.

Claims

WHAT IS CLAIMED IS:

1. A vaginal system for a female, comprising: an outer ring layer comprising a first silicone polymer; and a core comprising a second silicone polymer and a progestin, wherein the vaginal system comprises from about 10 mg to about 250 mg of the progestin, wherein, when the vaginal system is positioned in a vagina of the female, an amount of the progestin released per day from the vaginal system is from about 10 pg to about 150 pg during a steady state release period, and wherein the vaginal system is configured to release the progestin in the vagina for up to about 365 days or up to about 24 months.

2. The vaginal system of claim 1, wherein the vaginal system is configured to release the progestin in the vagina for up to about 365 days.

3. The vaginal system of claim 1 or 2, wherein the vaginal system comprises from about 40 mg to about 80 mg of the progestin.

4. The vaginal system of any one of claims 1-3, wherein, when the vaginal system is positioned in the vagina of the female, the amount of the progestin released per day from the vaginal system is from about 30 pg to about 50 pg during the steady state release period.

5. The vaginal system of any one of claims 1-4, wherein the progestin is etonogestrel.

6. The vaginal system of any one of claims 1-5, wherein the vaginal system comprises from about 0.1% w / w to about 1.0% w / w of the progestin.

7. The vaginal system of any one of claims 1-6, wherein the steady state release period immediately follows a transition phase of from about 7 days to about 28 days, wherein the transition phase immediately follows an initial release period of from about 0 days to about 7 days, and wherein the steady state release period lasts up to about 24 months or up to about 365 days after the vaginal system is positioned in the vagina.

8. The vaginal system of any one of claims 1-7, wherein the steady state release period lasts up to about 18 months after the vaginal system is positioned in the vagina.

9. The vaginal system of any one of claims 1-8, wherein the steady state release period lasts up to about 365 days after the vaginal system is positioned in the vagina.

10. The vaginal system of any one of claims 1-9, wherein an initial burst release of the vaginal system during the initial release period is equal to or less than about 360 pg / day.

11. The vaginal system of any one of claims 1-10, which is configured so that a release of the progestin during the steady state release period results in blood levels of the female of equal to or greater than about 140 pg / mL.

12. The vaginal system of any one of claims 1-11, which is configured so that the release of the progestin during the steady state release period results in the blood levels of the female of equal to or greater than about 90 pg / mL.

13. The vaginal system of any one of claims 1-12, wherein the vaginal system is configured to be positioned in the vagina of the female by the female.

14. The vaginal system of claim 13, wherein the vaginal system is configured to be removed from the vagina by the female.

15. The vaginal system of any one of claims 1-13, wherein the vaginal system is configured to be positioned in an upper third portion of the vagina of the female.

16. The vaginal system of any one of claims 1-15, wherein the vaginal system does not comprise any estrogen.

17. A method of contraception for a female in need thereof, comprising: positioning the vaginal system of any one of claims 1-16 in an upper third portion of the vagina of the female; and maintaining the vaginal system in situ of the female for up to about 365 days or up to about 24 months.

18. The method of claim 17, further comprising inserting the vaginal system into the vagina of the female by the female and removing the vaginal system from the vagina of the female by the female.

19. The method of claim 17 or 18, wherein the vaginal system releases the steady amount of the progestin during the steady state release period, which lasts up to about 24 months after the vaginal system is positioned in the vagina.

20. The method of claim 19, wherein the steady state release period lasts up to about 18 months after the vaginal system is positioned in the vagina.

21. The method of claim 19 or 20, wherein the steady state release period lasts up to about 365 days after the vaginal system is positioned in the vagina.

22. The method of any one of claims 19-21, wherein the steady state release period immediately follows a transition phase of from about 7 days to about 28 days, wherein the transition phase immediately follows an initial release period of from about 0 days to about 7 days, and the steady state release period lasts until the vaginal system is removed from the vagina.

23. The method of any one of claims 19-22, wherein an initial burst release of the vaginal system during the initial release period is equal to or less than about 360 pg / day.

24. The method of any one of claims 19-23, wherein a release of the progestin during the steady state release period results in blood levels of the female of equal to or greater than about 140 pg / mL.

25. The vaginal system of any one of claims 19-24, wherein a release of the progestin during the steady state release period results in blood levels of the female of equal to or greater than about 90 pg / mL.

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