MEDROXYPROGESTERONE ACETATE INJECTABLE COMPOSITIONS AND METHODS

OF USE

TECHNICAL FIELD

[0001] The disclosure is directed to long duration medroxyprogesterone acetate compositions for use in regions having extreme conditions such as high heat, high humidity, and unreliable electricity and refrigeration, that are suitable for subcutaneous injection.

BACKGROUND

[0002] Medroxyprogesterone acetate (MPA) has been approved in the United States for prevention of pregnancy in women of childbearing potential as well as for the management of endometriosis-associated pain. One such product, Depo-SubQ Provera 104® (medroxyprogesterone acetate injectable suspension) is provided as a single subcutaneous injection of 104 mg once every 12 to 14 weeks. The relatively short duration of action of this product requires four or more medical visits each year, which can impede patient compliance with the treatment protocol.

[0003] PCT publications WO2017/149492, W02019/048906 and W02019/049081 disclose certain subcutaneous compositions comprising MPA. However, development of a composition having an extended shelf life that can withstand the extreme conditions (e.g. heat up to about 50 °C, humidity over 75%, lack of electricity, inadequate refrigeration, and the like) present in many underdeveloped regions and developing countries in which women would benefit from a long acting contraceptive is challenging. A suitable composition having suitable resuspendability, sedimentation rate, viscosity, zeta potential, active pharmaceutical ingredient (API) soluble fraction, particle size distribution (PSD) and/or osmolality to withstand extreme conditions is not described in the art.

[0004] There is a need for new formulations of medroxyprogesterone acetate with a longer duration of action and shelf life that can withstand the extreme conditions present in many of the developing countries where longer duration of action formulations are needed.

SUMMARY

[0005] Optimized subcutaneous MPA-containing compositions having, e.g., a long duration of action as well as enhanced stability, extended shelf life, and good syringeability and injectability properties are described herein.

[0006] The present disclosure is directed to aqueous compositions for subcutaneous injection comprising, e.g., MPA at a concentration of about 260 mg/ml to 440 mg/ml, docusate sodium at a concentration of about 0.6 mg/ml to about 1.5 mg/ml, and polyethylene glycol. Methods of using these compositions are also described.

BRIEF DESCRIPTION OF THE DRAWINGS

[0007] FIG. 1 depicts mean plasma concentration time profiles of medroxyprogesterone acetate in rabbits up to 96 hours postdose.

[0008] FIG. 2 depicts mean plasma concentration time profiles of medroxyprogesterone acetate in rabbits up to day 365 postdose.

[0009] FIG. 3 is a plot of sedimentation rate (position in mm on the y-axis as a function of time in seconds on the x-axis), where the top two lines (plotted as circles and upright triangles) represent formulations with 400 mg/ml medroxyprogesterone acetate with a d(90) of 30 pm and where the bottom two lines (plotted as squares and downward-pointing triangles) represent formulations with 400 mg/ml medroxyprogesterone acetate with a d(90) of 9 pm.

DETAIFED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0010] The present disclosure may be understood more readily by reference to the following detailed description taken in connection with the accompanying figures and examples, which form a part of this disclosure. It is to be understood that this disclosure is not limited to the specific compositions or methods described and/or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed disclosure. Also, as used in the specification including the appended claims, the singular forms "a," "an," and "the" include the plural, and reference to a particular numerical value includes at least that particular value, unless the context clearly dictates otherwise. All ranges are inclusive and combinable.

A. General

[0011] The modifier "about" should be considered as disclosing the range defined by the absolute values of the two endpoints. For example, the expression "from about 2 to about 4" also discloses the range "from 2 to 4." When used to modify a single number, the term "about" may refer to plus or minus 10% of the indicated number and includes the indicated number. For example, "about 10%" may indicate a range of 9% to 11%, and "about 1" means from 0.9 to 1.1.

[0012] It is to be appreciated that certain features of the disclosure which are, for clarity, described herein in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any subcombination. Further, reference to values stated in ranges includes each and every value within that range.

[0013] As used herein, the term "composition" shall mean a composition that is made under conditions such that it is suitable for administration to humans, e.g., it is made under GMP conditions and contains pharmaceutically acceptable excipients, e.g., without limitation, stabilizers, bulking agents, buffers, carriers, diluents, vehicles, solubilizers, and binders. As used herein pharmaceutical composition includes, but is not limited to, a liquid form ready for subcutaneous injection or infusion.“Composition” and“formulation” are used interchangeably.

[0014] The compositions described herein comprise any one or more active pharmaceutical compounds. These active pharmaceutical compounds can include, for example, any agent for which extended release is desired. Such active pharmaceutical compounds can be used for the treatment of infectious diseases, cancer, psychiatric disorders, uterine disorders, and hormonal disorders, as well as for the prevention of pregnancy.

[0015] In preferred aspects, the compositions described herein comprise active pharmaceutical ingredients known in the art to be useful for preventing pregnancy or for treating endometriosis-associated pain, renal carcinoma, or endometrial carcinoma in a female patient. The active pharmaceutical ingredient may be selected by one skilled in the art depending on the condition being treated. Selection of the active pharmaceutical ingredient may also depend on other factors including, without limitation, components of the composition, mode of delivery, severity of the condition being treated, the patient’s age and weight, and any other active ingredients used in the composition. The compositions may contain one active pharmaceutical ingredient, two active pharmaceutical ingredients, or three or more active pharmaceutical ingredients. For example, the active pharmaceutical ingredient may be estrogen such as ethinyl estradiol or a progestin such as norethindrone, levonorgestrel, desogestrel, ethynidiol diacetate, norgestimate, norenthindrone acetate, norgestrel, drospirenone, norelgestromin or medroxyprogesterone acetate.

[0016] In preferred aspects, the compositions described herein for subcutaneous injection comprise medroxyprogesterone acetate. Medroxyprogesterone acetate may also be referred to by one of skill in the art as 6a-6-methyl-3,20-dioxopregna-4-en-l7-yl acetate, Pregna-4-ene-3,20-dione, l7-(acetyloxy)-6-methyl,6(a), or 17 alpha-hydroxy-6(a)-methylpregn-4-ene 3,20-dione acetate. Concentrations of medroxyprogesterone acetate in the compositions can range from about 260 mg/ml to 440 mg/ml. For example, the concentrations can range from about 260

mg/ml to 440 mg/ml, 265 mg/ml to 440 mg/ml, 270 mg/ml to 440 mg/ml, 275 mg/ml to 440 mg/ml, 280 mg/ml to 440 mg/ml, 285 mg/ml to 440 mg/ml, 290 mg/ml to 440 mg/ml, 295 mg/ml to 440 mg/ml, 300 mg/ml to 440 mg/ml, 305 mg/ml to 440 mg/ml, 310 mg/ml to 440 mg/ml, 315 mg/ml to 440 mg/ml, 320 mg/ml to 440 mg/ml, 325 mg/ml to 440 mg/ml, 330 mg/ml to 440 mg/ml, 335 mg/ml to 440 mg/ml, 340 mg/ml to 440 mg/ml, 345 mg/ml to 440 mg/ml, 350 mg/ml to 440 mg/ml, 355 mg/ml to 440 mg/ml, 360 mg/ml to 440 mg/ml, 365 mg/ml to 440 mg/ml, 370 mg/ml to 440 mg/ml, 375 mg/ml to 440 mg/ml, 380 mg/ml to 440 mg/ml, 385 mg/ml to 440 mg/ml, 390 mg/ml to 440 mg/ml, 395 mg/ml to 440 mg/ml, 400 mg/ml to 440 mg/ml, 405 mg/ ml to 440 mg/ml, 410 mg/ml to 440 mg/ml, 415 mg/ml to 440 mg/ml, 420 mg/ml to 440 mg/ml,

425 mg/ml to 440 mg/ml, 430 mg/ml to 440 mg/ml, 435 mg/ml to 440 mg/ml, 260 mg/ml to 435 mg/ml, 265 mg/ml to 435 mg/ml, 270 mg/ml to 435 mg/ml, 275 mg/ml to 435 mg/ml, 280 mg/ml to 435 mg/ml, 285 mg/ml to 435 mg/ml, 290 mg/ml to 435 mg/ml, 295 mg/ml to 435 mg/ml, 300 mg/ml to 435 mg/ml, 305 mg/ml to 435 mg/ml, 310 mg/ml to 435 mg/ml, 315 mg/ml to 435 mg/ml, 320 mg/ml to 435 mg/ml, 325 mg/ml to 435 mg/ml, 330 mg/ml to 435 mg/ml, 335 mg/ml to 435 mg/ml, 340 mg/ml to 435 mg/ml, 345 mg/ml to 435 mg/ml, 350 mg/ml to 435 mg/ml, 355 mg/ml to 435 mg/ml, 360 mg/ml to 435 mg/ml, 365 mg/ml to 435 mg/ml, 370 mg/ml to 435 mg/ml, 375 mg/ml to 435 mg/ml, 380 mg/ml to 435 mg/ml, 385 mg/ml to 435 mg/ml, 390 mg/ml to 435 mg/ml, 395 mg/ml to 435 mg/ml, 400 mg/ml to 435 mg/ml, 405 mg/ ml to 435 mg/ml,

410 mg/ml to 435 mg/ml, 415 mg/ml to 435 mg/ml, 420 mg/ml to 435 mg/ml, 425 mg/ml to 435 mg/ml, 430 mg/ml to 435 mg/ml, 260 mg/ml to 430 mg/ml, 265 mg/ml to 430 mg/ml, 270 mg/ml to 430 mg/ml, 275 mg/ml to 430 mg/ml, 280 mg/ml to 430 mg/ml, 285 mg/ml to 430 mg/ml, 290 mg/ml to 430 mg/ml, 295 mg/ml to 430 mg/ml, 300 mg/ml to 430 mg/ml, 305 mg/ml to 430 mg/ml, 310 mg/ml to 430 mg/ml, 315 mg/ml to 430 mg/ml, 320 mg/ml to 430 mg/ml, 325 mg/ml to 430 mg/ml, 330 mg/ml to 430 mg/ml, 335 mg/ml to 430 mg/ml, 340 mg/ml to 430 mg/ml, 345 mg/ml to 430 mg/ml, 350 mg/ml to 430 mg/ml, 355 mg/ml to 430 mg/ml, 360 mg/ml to 430 mg/ml, 365 mg/ml to 430 mg/ml, 370 mg/ml to 430 mg/ml, 375 mg/ml to 430 mg/ml, 380 mg/ml to 430 mg/ml, 385 mg/ml to 430 mg/ml, 390 mg/ml to 430 mg/ml, 395 mg/ml to 430 mg/ml, 400 mg/ml to 430 mg/ml, 405 mg/ ml to 430 mg/ml, 410 mg/ml to 430 mg/ml, 415 mg/ml to 430 mg/ml, 420 mg/ml to 430 mg/ml, 425 mg/ml to 430 mg/ml, 260 mg/ml to 425 mg/ml, 265 mg/ml to 425 mg/ml, 270 mg/ml to 425 mg/ml, 275 mg/ml to 425 mg/ml, 280 mg/ml to 425 mg/ml, 285 mg/ml to 425 mg/ml, 290 mg/ml to 425 mg/ml, 295 mg/ml to 425 mg/ml, 300 mg/ml to 425 mg/ml, 305 mg/ml to 425 mg/ml, 310 mg/ml to 425 mg/ml, 315 mg/ml to 425 mg/ml, 320 mg/ml to 425 mg/ml, 325 mg/ml to 425 mg/ml, 330 mg/ml to 425 mg/ml, 335 mg/ml to 425 mg/ml, 340 mg/ml to 425 mg/ml, 345 mg/ml to 425 mg/ml, 350 mg/ml to 425 mg/ml, 355 mg/ml to 425 mg/ml, 360 mg/ml to 425 mg/ml, 365 mg/ml to 425 mg/ml, 370 mg/ml to 425 mg/ml, 375 mg/ml to 425 mg/ml, 380 mg/ml to 425 mg/ml, 385 mg/ml to 425 mg/ml, 390 mg/ml to 425 mg/ml, 395 mg/ml to 425 mg/ml, 400 mg/ml to 425 mg/ml, 405 mg/ ml to 425 mg/ml, 410 mg/ml to 425 mg/ml, 415 mg/ml to 425 mg/ml, 420 mg/ml to 425 mg/ml, 260 mg/ml to 420 mg/ml, 265 mg/ml to 420 mg/ml, 270 mg/ml to 420 mg/ml, 275 mg/ml to 420 mg/ml, 280 mg/ml to 420 mg/ml, 285 mg/ml to 420 mg/ml, 290 mg/ml to 420 mg/ml, 295 mg/ml to 420 mg/ml, 300 mg/ml to 420 mg/ml, 305 mg/ml to 420 mg/ml, 310 mg/ml to 420 mg/ml, 315 mg/ml to 420 mg/ml, 320 mg/ml to 420 mg/ml, 325 mg/ml to 420 mg/ml, 330 mg/ml to 420 mg/ml, 335 mg/ml to 420 mg/ml, 340 mg/ml to 420 mg/ml, 345 mg/ml to 420 mg/ml, 350 mg/ml to 420 mg/ml, 355 mg/ml to 420 mg/ml, 360 mg/ml to 420 mg/ml, 365 mg/ml to 420 mg/ml, 370 mg/ml to 420 mg/ml, 375 mg/ml to 420 mg/ml, 380 mg/ml to 420 mg/ml, 385 mg/ml to 420 mg/ml, 390 mg/ml to 420 mg/ml, 395 mg/ml to 420 mg/ml, 400 mg/ml to 420 mg/ml, 405 mg/ ml to 420 mg/ml, 410 mg/ml to 420 mg/ml, 415 mg/ml to 420 mg/ml, 260 mg/ml to 415 mg/ml, 265 mg/ml to 415 mg/ml, 270 mg/ml to 415 mg/ml, 275 mg/ml to 415 mg/ml, 280 mg/ml to 415 mg/ml, 285 mg/ml to 415 mg/ml, 290 mg/ml to 415 mg/ml, 295 mg/ml to 415 mg/ml, 300 mg/ml to 415 mg/ml, 305 mg/ml to 415 mg/ml, 310 mg/ml to 415 mg/ml, 315 mg/ml to 415 mg/ml, 320 mg/ml to 415 mg/ml, 325 mg/ml to 415 mg/ml, 330 mg/ml to 415 mg/ml, 335 mg/ml to 415 mg/ml, 340 mg/ml to 415 mg/ml, 345 mg/ml to 415 mg/ml, 350 mg/ml to 415 mg/ml, 355 mg/ml to 415 mg/ml, 360 mg/ml to 415 mg/ml, 365 mg/ml to 415 mg/ml, 370 mg/ml to 415 mg/ml, 375 mg/ml to 415 mg/ml, 380 mg/ml to 415 mg/ml, 385 mg/ml to 415 mg/ml, 390 mg/ml to 415 mg/ml, 395 mg/ml to 415 mg/ml, 400 mg/ml to 415 mg/ml, 405 mg/ ml to 415 mg/ml, 410 mg/ml to 415 mg/ml, 260 mg/ml to 410 mg/ml, 265 mg/ml to 410 mg/ml, 270 mg/ml to 410 mg/ml, 275 mg/ml to 410 mg/ml, 280 mg/ml to 410 mg/ml, 285 mg/ml to 410 mg/ml, 290 mg/ml to 410 mg/ml, 295 mg/ml to 410 mg/ml, 300 mg/ml to 410 mg/ml, 305 mg/ml to 410 mg/ml, 310 mg/ml to 410 mg/ml, 315 mg/ml to 410 mg/ml, 320 mg/ml to 410 mg/ml, 325 mg/ml to 410 mg/ml, 330 mg/ml to 410 mg/ml, 335 mg/ml to 410 mg/ml, 340 mg/ml to 410 mg/ml, 345 mg/ml to 410 mg/ml, 350 mg/ml to 410 mg/ml, 355 mg/ml to 410 mg/ml, 360 mg/ml to 410 mg/ml, 365 mg/ml to 410 mg/ml, 370 mg/ml to 410 mg/ml, 375 mg/ml to 410 mg/ml, 380 mg/ml to 410 mg/ml, 385 mg/ml to 410 mg/ml, 390 mg/ml to 410 mg/ml, 395 mg/ml to 410 mg/ml, 400 mg/ml to 410 mg/ml, 405 mg/ ml to 410 mg/ml,

260 mg/ml to 405 mg/ml, 265 mg/ml to 405 mg/ml, 270 mg/ml to 405 mg/ml, 275 mg/ml to 405 mg/ml, 280 mg/ml to 405 mg/ml, 285 mg/ml to 405 mg/ml, 290 mg/ml to 405 mg/ml, 295 mg/ml to 405 mg/ml, 300 mg/ml to 405 mg/ml, 305 mg/ml to 405 mg/ml, 310 mg/ml to 405 mg/ml, 315 mg/ml to 405 mg/ml, 320 mg/ml to 405 mg/ml, 325 mg/ml to 405 mg/ml, 330 mg/ml to 405 mg/ml, 335 mg/ml to 405 mg/ml, 340 mg/ml to 405 mg/ml, 345 mg/ml to 405 mg/ml, 350 mg/ml to 405 mg/ml, 355 mg/ml to 405 mg/ml, 360 mg/ml to 405 mg/ml, 365 mg/ml to 405 mg/ml, 370 mg/ml to 405 mg/ml, 375 mg/ml to 405 mg/ml, 380 mg/ml to 405 mg/ml, 385 mg/ml to 405 mg/ml, 390 mg/ml to 405 mg/ml, 395 mg/ml to 405 mg/ml, 260 mg/ml to 400 mg/ml, 265 mg/ml to 400 mg/ml, 270 mg/ml to 400 mg/ml, 275 mg/ml to 400 mg/ml, 280 mg/ml to 400 mg/ml, 285 mg/ml to 400 mg/ml, 290 mg/ml to 400 mg/ml, 295 mg/ml to 400 mg/ml, 300 mg/ml to 400 mg/ml, 305 mg/ml to 400 mg/ml, 310 mg/ml to 400 mg/ml, 315 mg/ml to 400 mg/ml, 320 mg/ml to 400 mg/ml, 325 mg/ml to 400 mg/ml, 330 mg/ml to 400 mg/ml, 335 mg/ml to 400 mg/ml, 340 mg/ml to 400 mg/ml, 345 mg/ml to 400 mg/ml, 350 mg/ml to 400 mg/ml, 355 mg/ml to 400 mg/ml, 360 mg/ml to 400 mg/ml, 365 mg/ml to 400 mg/ml, 370 mg/ml to 400 mg/ml, 375 mg/ml to 400 mg/ml, 380 mg/ml to 400 mg/ml, 385 mg/ml to 400 mg/ml, 390 mg/ml to 400 mg/ml, 395 mg/ml to 400 mg/ml, 260 mg/ml to 395 mg/ml, 265 mg/ml to 395 mg/ml, 270 mg/ml to 395 mg/ml, 275 mg/ml to 395 mg/ml, 280 mg/ml to 395 mg/ml, 285 mg/ml to 395 mg/ml, 290 mg/ml to 395 mg/ml, 295 mg/ml to 395 mg/ml, 300 mg/ml to 395 mg/ml, 305 mg/ml to 395 mg/ml, 310 mg/ml to 395 mg/ml, 315 mg/ml to 395 mg/ml, 320 mg/ml to 395 mg/ml, 325 mg/ml to 395 mg/ml, 330 mg/ml to 395 mg/ml, 335 mg/ml to 395 mg/ml, 340 mg/ml to 395 mg/ml, 345 mg/ml to 395 mg/ml, 350 mg/ml to 395 mg/ml, 355 mg/ml to 395 mg/ml, 360 mg/ml to 395 mg/ml, 365 mg/ml to 395 mg/ml, 370 mg/ml to 395 mg/ml, 375 mg/ml to 395 mg/ml, 380 mg/ml to 395 mg/ml, 385 mg/ml to 395 mg/ml, 390 mg/ml to 395 mg/ml, 260 mg/ml to 390 mg/ml, 265 mg/ml to 390 mg/ml, 270 mg/ml to 390 mg/ml, 275 mg/ml to 390 mg/ml, 280 mg/ml to 390 mg/ml, 285 mg/ml to 390 mg/ml, 290 mg/ml to 390 mg/ml, 295 mg/ml to 390 mg/ml, 300 mg/ml to 390 mg/ml, 305 mg/ml to 390 mg/ml, 310 mg/ml to 390 mg/ml, 315 mg/ml to 390 mg/ml, 320 mg/ml to 390 mg/ml, 325 mg/ml to 390 mg/ml, 330 mg/ml to 390 mg/ml, 335 mg/ml to 390 mg/ml, 340 mg/ml to 390 mg/ml, 345 mg/ml to 390 mg/ml, 350 mg/ml to 390 mg/ml, 355 mg/ml to 390 mg/ml, 360 mg/ml to 390 mg/ml, 365 mg/ml to 390 mg/ml, 370 mg/ml to 390 mg/ml, 375 mg/ml to 390 mg/ml, 380 mg/ml to 390 mg/ml, 385 mg/ml to 390 mg/ml, 260 mg/ml to 385 mg/ml, 265 mg/ml to 385 mg/ml, 270 mg/ml to 385 mg/ml, 275 mg/ml to 385 mg/ml, 280 mg/ml to 385 mg/ml, 285 mg/ml to 385 mg/ml, 290 mg/ml to 385 mg/ml, 295 mg/ml to 385 mg/ml, 300 mg/ml to 385 mg/ml, 305 mg/ml to 385 mg/ml, 310 mg/ml to 385 mg/ml, 315 mg/ml to 385 mg/ml, 320 mg/ml to 385 mg/ml, 325 mg/ml to 385 mg/ml, 330 mg/ml to 385 mg/ml, 335 mg/ml to 385 mg/ml, 340 mg/ml to 385 mg/ml, 345 mg/ml to 385 mg/ml, 350 mg/ml to 385 mg/ml, 355 mg/ml to 385 mg/ml, 360 mg/ml to 385 mg/ml, 365 mg/ml to 385 mg/ml, 370 mg/ml to 385 mg/ml, 375 mg/ml to 385 mg/ml, 380 mg/ml to 385 mg/ml, 260 mg/ml to 380 mg/ml, 265 mg/ml to 380 mg/ml, 270 mg/ml to 380 mg/ml, 275 mg/ml to 380 mg/ml, 280 mg/ml to 380 mg/ml, 285 mg/ml to 380 mg/ml, 290 mg/ml to 380 mg/ml, 295 mg/ml to 380 mg/ml, 300 mg/ml to 380 mg/ml, 305 mg/ml to 380 mg/ml, 310 mg/ml to 380 mg/ml, 315 mg/ml to 380 mg/ml, 320 mg/ml to 380 mg/ml, 325 mg/ml to 380 mg/ml, 330 mg/ml to 380 mg/ml, 335 mg/ml to 380 mg/ml, 340 mg/ml to 380 mg/ml, 345 mg/ml to 380 mg/ml, 350 mg/ml to 380 mg/ml, 355 mg/ml to 380 mg/ml, 360 mg/ml to 380 mg/ml, 365 mg/ml to 380 mg/ml, 370 mg/ml to 380 mg/ml, 375 mg/ml to 380 mg/ml, 260 mg/ml to 375 mg/ml, 265 mg/ml to 375 mg/ml, 270 mg/ml to 375 mg/ml, 275 mg/ml to 375 mg/ml, 280 mg/ml to 375 mg/ml, 285 mg/ml to 375 mg/ml, 290 mg/ml to 375 mg/ml, 295 mg/ml to 375 mg/ml, 300 mg/ml to 375 mg/ml, 305 mg/ml to 375 mg/ml, 310 mg/ml to 375 mg/ml, 315 mg/ml to 375 mg/ml, 320 mg/ml to 375 mg/ml, 325 mg/ml to 375 mg/ml, 330 mg/ml to 375 mg/ml, 335 mg/ml to 375 mg/ml, 340 mg/ml to 375 mg/ml, 345 mg/ml to 375 mg/ml, 350 mg/ml to 375 mg/ml, 355 mg/ml to 375 mg/ml, 360 mg/ml to 375 mg/ml, 365 mg/ml to 375 mg/ml, 370 mg/ml to 375 mg/ml, 260 mg/ml to 370 mg/ml, 265 mg/ml to 370 mg/ml, 270 mg/ml to 370 mg/ml, 275 mg/ml to 370 mg/ml, 280 mg/ml to 370 mg/ml, 285 mg/ml to 370 mg/ml, 290 mg/ml to 370 mg/ml, 295 mg/ml to 370 mg/ml, 300 mg/ml to 370 mg/ml, 305 mg/ml to 370 mg/ml, 310 mg/ml to 370 mg/ml, 315 mg/ml to 370 mg/ml, 320 mg/ml to 370 mg/ml, 325 mg/ml to 370 mg/ml, 330 mg/ml to 370 mg/ml, 335 mg/ml to 370 mg/ml, 340 mg/ml to 370 mg/ml, 345 mg/ml to 370 mg/ml, 350 mg/ml to 370 mg/ml, 355 mg/ml to 370 mg/ml, 360 mg/ml to 370 mg/ml, 365 mg/ml to 370 mg/ml, 260 mg/ml to 365 mg/ml, 265 mg/ml to 365 mg/ml, 270 mg/ml to 365 mg/ml, 275 mg/ml to 365 mg/ml, 280 mg/ml to 365 mg/ml, 285 mg/ml to 365 mg/ml, 290 mg/ml to 365 mg/ml, 295 mg/ml to 365 mg/ml, 300 mg/ml to 365 mg/ml, 305 mg/ml to 365 mg/ml, 310 mg/ml to 365 mg/ml, 315 mg/ml to 365 mg/ml, 320 mg/ml to 365 mg/ml, 325 mg/ml to 365 mg/ml, 330 mg/ml to 365 mg/ml, 335 mg/ml to 365 mg/ml, 340 mg/ml to 365 mg/ml, 345 mg/ml to 365 mg/ml, 350 mg/ml to 365 mg/ml, 355 mg/ml to 365 mg/ml, 360 mg/ml to 365 mg/ml, 260 mg/ml to 360 mg/ml, 265 mg/ml to 360 mg/ml, 270 mg/ml to 360 mg/ml, 275 mg/ml to 360 mg/ml, 280 mg/ml to 360 mg/ml, 285 mg/ml to 360 mg/ml, 290 mg/ml to 360 mg/ml, 295 mg/ml to 360 mg/ml, 300 mg/ml to 360 mg/ml, 305 mg/ml to 360 mg/ml, 310 mg/ml to 360 mg/ml, 315 mg/ml to 360 mg/ml, 320 mg/ml to 360 mg/ml, 325 mg/ml to 360 mg/ml, 330 mg/ml to 360 mg/ml, 335 mg/ml to 360 mg/ml, 340 mg/ml to 360 mg/ml, 345 mg/ml to 360 mg/ml, 350 mg/ml to 360 mg/ml, 355 mg/ml to 360 mg/ml, 260 mg/ml to 350 mg/ml, 265 mg/ml to 350 mg/ml, 270 mg/ml to 350 mg/ml, 275 mg/ml to 350 mg/ml, 280 mg/ml to 350 mg/ml, 285 mg/ml to 350 mg/ml, 290 mg/ml to 350 mg/ml, 295 mg/ml to 350 mg/ml, 300 mg/ml to 350 mg/ml, 305 mg/ml to 350 mg/ml, 310 mg/ml to 350 mg/ml, 315 mg/ml to 350 mg/ml, 320 mg/ml to 350 mg/ml, 325 mg/ml to 350 mg/ml, 330 mg/ml to 350 mg/ml, 335 mg/ml to 350 mg/ml, 340 mg/ml to 350 mg/ml, 345 mg/ml to 350 mg/ml, 260 mg/ml to 340 mg/ml, 265 mg/ml to 340 mg/ml, 270 mg/ml to 340 mg/ml, 275 mg/ml to 340 mg/ml, 280 mg/ml to 340 mg/ml, 285 mg/ml to 340 mg/ml, 290 mg/ml to 340 mg/ml, 295 mg/ml to 340 mg/ml, 300 mg/ml to 340 mg/ml, 305 mg/ml to 340 mg/ml, 310 mg/ml to 340 mg/ml, 315 mg/ml to 340 mg/ml, 320 mg/ml to 340 mg/ml, 325 mg/ml to 340 mg/ml, 330 mg/ml to 340 mg/ml, 335 mg/ml to 340 mg/ml, 260 mg/ml to 330 mg/ml, 265 mg/ml to 330 mg/ml, 270 mg/ml to 330 mg/ml, 275 mg/ml to 330 mg/ml, 280 mg/ml to 330 mg/ml, 285 mg/ml to 330 mg/ml, 290 mg/ml to 330 mg/ml, 295 mg/ml to 330 mg/ml, 300 mg/ml to 330 mg/ml, 305 mg/ml to 330 mg/ml, 310 mg/ml to 330 mg/ml, 315 mg/ml to 330 mg/ml, 320 mg/ml to 330 mg/ml, 325 mg/ml to 330 mg/ml, 260 mg/ml to 320 mg/ml, 265 mg/ml to 320 mg/ml, 270 mg/ml to 320 mg/ml, 275 mg/ml to 320 mg/ml, 280 mg/ml to 320 mg/ml, 285 mg/ml to 320 mg/ml, 290 mg/ml to 320 mg/ml, 295 mg/ml to 320 mg/ml, 300 mg/ml to 320 mg/ml, 305 mg/ml to 320 mg/ml, 310 mg/ml to 320 mg/ml, 315 mg/ml to 320 mg/ml, 260 mg/ml to 310 mg/ml, 265 mg/ml to 310 mg/ml, 270 mg/ml to 310 mg/ml, 275 mg/ml to 310 mg/ml, 280 mg/ml to 310 mg/ml, 285 mg/ml to 310 mg/ml, 290 mg/ml to 310 mg/ml, 295 mg/ml to 310 mg/ml, 300 mg/ml to 310 mg/ml, 305 mg/ml to 310 mg/ml, 260 mg/ml to 310 mg/ml, 265 mg/ml to 300 mg/ml, 270 mg/ml to 300 mg/ml, 275 mg/ml to 300 mg/ml, 280 mg/ml to 300 mg/ml, 285 mg/ml to 300 mg/ml, 290 mg/ml to 300 mg/ml, 295 mg/ml to 300 mg/ml, 265 mg/ml to 290 mg/ml, 270 mg/ml to 290 mg/ml, 275 mg/ml to 290 mg/ml, 280 mg/ml to 290 mg/ml, 285 mg/ml to 290 mg/ml, 265 mg/ml to 280 mg/ml, 270 mg/ml to 280 mg/ml, 275 mg/ml to 280 mg/ml, or about 265 mg/ml to 270 mg/ml. The medroxyprogesterone acetate ranges disclosed in this paragraph are hereby disclosed in combination with the docusate sodium and/or polyethylene glycol ranges disclosed herein. Thus the medroxyprogesterone acetate ranges disclosed in this paragraph are hereby disclosed in combination with a docusate sodium concentration of about 0.6 mg/ml to about 1.5 mg/ml and optionally a polyethylene glycol concentration of about 10 mg/ml to about 40 mg/ml or about 15 mg/ml to about 30 mg/ml. For the sake of brevity, all of the combinations are not being parsed out.

[0017] By way of further example, concentrations of medroxyprogesterone acetate (mg/ml) in the composition can comprise about 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290,

291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309,

310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328,

329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347,

348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360 360, 361, 362, 363, 364, 365,

366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384,

385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403,

404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439 or about 440 mg/ml. The medroxyprogesterone acetate concentrations disclosed in this paragraph are hereby disclosed in combination with the docusate sodium and/or polyethylene glycol ranges disclosed herein. Thus the medroxyprogesterone acetate ranges disclosed in this paragraph are hereby disclosed in combination with a docusate sodium concentration of about 0.5 mg/ml to about 3 mg/ml, about 0.5 mg/ml to about 1.0 mg/ml or about 0.5 to 0.7 mg/ml, and optionally a polyethylene glycol concentration of about 10 mg/ml to about 40 mg/ml or about 15 mg/ml to about 30 mg/ml. For the sake of brevity, all of the combinations are not being parsed out.

[0018] In other aspects, the concentration of medroxyprogesterone acetate in the compositions can range from about 160 mg/ml to 240 mg/ml. For example, the concentrations can range from about 160 mg/ml to 240 mg/ml, 165 mg/ml to 240 mg/ml, 170 mg/ml to 240 mg/ml, 175 mg/ml to 240 mg/ml, 180 mg/ml to 240 mg/ml, 185 mg/ml to 240 mg/ml, 190 mg/ml to 240 mg/ml, 195 mg/ml to 240 mg/ml, 200 mg/ml to 240 mg/ml, 205 mg/ml to 240 mg/ml, 210 mg/ml to 240 mg/ml, 215 mg/ml to 240 mg/ml, 220 mg/ml to 240 mg/ml, 225 mg/ml to 240 mg/ml, 230 mg/ml to 240 mg/ml, 235 mg/ml to 240 mg/ml, 160 mg/ml to 235 mg/ml, 165 mg/ml to 235 mg/ml, 170 mg/ml to 235 mg/ml, 175 mg/ml to 235 mg/ml, 180 mg/ml to 235 mg/ml, 185 mg/ml to 235 mg/ml, 190 mg/ml to 235 mg/ml, 195 mg/ml to 235 mg/ml, 200 mg/ml to 235 mg/ml, 205 mg/ml to 235 mg/ml, 210 mg/ml to 235 mg/ml, 215 mg/ml to 235 mg/ml, 220 mg/ml to 235 mg/ml, 225 mg/ml to 235 mg/ml, 230 mg/ml to 235 mg/ml, 160 mg/ml to 230 mg/ml, 165 mg/ml to 230 mg/ml, 170 mg/ml to 230 mg/ml, 175 mg/ml to 230 mg/ml, 180 mg/ml to 230 mg/ml, 185 mg/ml to 230 mg/ml, 190 mg/ml to 230 mg/ml, 195 mg/ml to 230 mg/ml, 200 mg/ml to 230 mg/ml, 205 mg/ml to 230 mg/ml, 210 mg/ml to 230 mg/ml, 215 mg/ml to 230 mg/ml, 220 mg/ml to 230 mg/ml, 225 mg/ml to 230 mg/ml, 160 mg/ml to 225 mg/ml, 165 mg/ml to 225 mg/ml, 170 mg/ml to 225 mg/ml, 175 mg/ml to 225 mg/ml, 180 mg/ml to 225 mg/ml, 185 mg/ml to 225 mg/ml, 190 mg/ml to 225 mg/ml, 195 mg/ml to 225 mg/ml, 200 mg/ml to 225 mg/ml, 205 mg/ml to 225 mg/ml, 210 mg/ml to 225 mg/ml, 215 mg/ml to 225 mg/ml, 220 mg/ml to 225 mg/ml, 160 mg/ml to 220 mg/ml, 165 mg/ml to 220 mg/ml, 170 mg/ml to 220 mg/ml, 175 mg/ml to 220 mg/ml, 180 mg/ml to 220 mg/ml, 185 mg/ml to 220 mg/ml, 190 mg/ml to 220 mg/ml, 195 mg/ml to 220 mg/ml, 200 mg/ml to 220 mg/ml, 205 mg/ml to 220 mg/ml, 210 mg/ml to 220 mg/ml, 215 mg/ml to 220 mg/ml, 160 mg/ml to 215 mg/ml, 165 mg/ml to 215 mg/ml, 170 mg/ml to 215 mg/ml, 175 mg/ml to 215 mg/ml, 180 mg/ml to 215 mg/ml, 185 mg/ml to 215 mg/ml, 190 mg/ml to 215 mg/ml, 195 mg/ml to 215 mg/ml, 200 mg/ml to 215 mg/ml, 205 mg/ml to 215 mg/ml, 210 mg/ml to 215 mg/ml, 160 mg/ml to 210 mg/ml, 165 mg/ml to 210 mg/ml, 170 mg/ml to 210 mg/ml, 175 mg/ml to 210 mg/ml, 180 mg/ml to 210 mg/ml, 185 mg/ml to 210 mg/ml, 190 mg/ml to 210

mg/ml, 195 mg/ml to 210 mg/ml, 200 mg/ml to 210 mg/ml, 205 mg/ml to 210 mg/ml, 160 mg/ml to 205 mg/ml, 165 mg/ml to 205 mg/ml, 170 mg/ml to 205 mg/ml, 175 mg/ml to 205 mg/ml, 180 mg/ml to 205 mg/ml, 185 mg/ml to 205 mg/ml, 190 mg/ml to 205 mg/ml, 195 mg/ml to 205 mg/ml, 200 mg/ml to 205 mg/ml, 160 mg/ml to 200 mg/ml, 165 mg/ml to 200 mg/ml, 170 mg/ml to 200 mg/ml, 175 mg/ml to 200 mg/ml, 180 mg/ml to 200 mg/ml, 185 mg/ml to 200 mg/ml, 190 mg/ml to 200 mg/ml, 195 mg/ml to 200 mg/ml, 160 mg/ml to 195 mg/ml, 165 mg/ml to 195 mg/ml, 170 mg/ml to 195 mg/ml, 175 mg/ml to 195 mg/ml, 180 mg/ml to 195 mg/ml, 185 mg/ml to 195 mg/ml, 190 mg/ml to 195 mg/ml, 160 mg/ml to 190 mg/ml, 165 mg/ml to 190 mg/ml, 170 mg/ml to 190 mg/ml, 175 mg/ml to 190 mg/ml, 180 mg/ml to 190 mg/ml, 185 mg/ml to 190 mg/ml, 160 mg/ml to 185 mg/ml, 165 mg/ml to 185 mg/ml, 170 mg/ml to 185 mg/ml, 175 mg/ml to 185 mg/ml, 180 mg/ml to 185 mg/ml, 160 mg/ml to 180 mg/ml, 165 mg/ml to 180 mg/ml, 170 mg/ml to 180 mg/ml, 175 mg/ml to 180 mg/ml, 160 mg/ml to 175 mg/ml, 165 mg/ml to 175 mg/ml, 170 mg/ml to 175 mg/ml, 160 mg/ml to 170 mg/ml, 165 mg/ml to 170 mg/ml, or about 160 mg/ml to 165 mg/ml. The medroxyprogesterone acetate ranges disclosed in this paragraph are hereby disclosed in combination with the docusate sodium and/or polyethylene glycol ranges disclosed herein, preferably in combination with a docusate sodium concentration of about 0.5 mg/ml to about 3 mg/ml or about 0.6 mg/ml to about 1.5 mg/ml and optionally a polyethylene glycol concentration of about 10 mg/ml to about 40 mg/ml or about 15 mg/ml to about 30 mg/ml. . For the sake of brevity, all of the combinations are not being parsed out.

[0019] By way of further example, concentrations of medroxyprogesterone acetate in the composition can comprise about 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191,

192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210,

211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229,

230, 231, 232, 233, 234, 235, 236, 237, 238, 239, or about 240 mg/ml. The medroxyprogesterone acetate concentrations disclosed in this paragraph are hereby disclosed in combination with the docusate sodium and/or polyethylene glycol ranges disclosed herein, preferably in combination with a docusate sodium concentration of about 1.2 mg/ml to 3 mg/ml and optionally a polyethylene glycol concentration of about 10 mg/ml to 40 mg/ml. For the sake of brevity, all of the combinations are not being parsed out.

[0020] The compositions of the disclosure further comprise docusate sodium. As used herein,

“docusate sodium” refers to the excipient with the molecular formula C2oH37Na07S, and may also be referred to by one of skill in the art as dioctyl sodium sulfosuccinate or DSS. The compositions of the disclosure may comprise a concentration of docusate sodium that ranges from about 0.5 mg/ml to about 3.0 mg/ml. In certain embodiments, the concentration of docusate sodium can range from about 0.6 mg/ml to about 1.5 mg/ml. For example, the concentrations can range from about 0.5 mg/ml to 3.0 mg/ml, 0.6 mg/ml to 3.0 mg/ml, 0.7 mg/ml to 3.0 mg/ml, 0.8 mg/ml to 3.0 mg/ml, 0.9 mg/ml to 3.0 mg/ml, 1.0 mg/ml to 3.0 mg/ml, 1.1 mg/ml to 3.0 mg/ml, 1.2 mg/ml to 3.0 mg/ml, 1.3 mg/ml to 3.0 mg/ml, 1.4 mg/ml to 3.0 mg/ml,

1.5 mg/ml to 3.0 mg/ml, 1.6 mg/ml to 3.0 mg/ml, 1.7 mg/ml to 3.0 mg/ml, 1.8 mg/ml to 3.0 mg/ml, 1.9 mg/ml to 3.0 mg/ml, 2.0 mg/ml to 3.0 mg/ml, 2.1 mg/ml to 3.0 mg/ml, 2.2 mg/ml to 3.0 mg/ml, 2.3 mg/ml to 3.0 mg/ml, 2.4 mg/ml to 3.0 mg/ml, 2.5 mg/ml to 3.0 mg/ml, 2.6 mg/ml to 3.0 mg/ml, 2.7 mg/ml to 3.0 mg/ml, 2.8 mg/ml to 3.0 mg/ml, 2.9 mg/ml to 3.0 mg/ml, 0.5 mg/ml to 2.9 mg/ml, 0.6 mg/ml to 2.9 mg/ml, 0.7 mg/ml to 2.9 mg/ml, 0.8 mg/ml to 2.9 mg/ml, 0.9 mg/ml to 2.9 mg/ml, 1.0 mg/ml to 2.9 mg/ml, 1.1 mg/ml to 2.9 mg/ml, 1.2 mg/ml to 2.9 mg/ml, 1.3 mg/ml to 2.9 mg/ml, 1.4 mg/ml to 2.9 mg/ml, 1.5 mg/ml to 2.9 mg/ml, 1.6 mg/ml to 2.9 mg/ml, 1.7 mg/ml to 2.9 mg/ml, 1.8 mg/ml to 2.9 mg/ml, 1.9 mg/ml to 2.9 mg/ml, 2.0 mg/ml to 2.9 mg/ml, 2.1 mg/ml to 2.9 mg/ml, 2.2 mg/ml to 2.9 mg/ml, 2.3 mg/ml to 2.9 mg/ml, 2.4 mg/ml to 2.9 mg/ml, 2.5 mg/ml to 2.9 mg/ml, 2.6 mg/ml to 2.9 mg/ml, 2.7 mg/ml to 2.9 mg/ml, 2.8 mg/ml to 2.9 mg/ml, 0.5 mg/ml to 2.8 mg/ml, 0.6 mg/ml to 2.8 mg/ml, 0.7 mg/ml to 2.8 mg/ml, 0.8 mg/ml to 2.8 mg/ml, 0.9 mg/ml to 2.8 mg/ml, 1.0 mg/ml to 2.8 mg/ml, 1.1 mg/ml to

2.8 mg/ml, 1.2 mg/ml to 2.8 mg/ml, 1.3 mg/ml to 2.8 mg/ml, 1.4 mg/ml to 2.8 mg/ml, 1.5 mg/ml to 2.8 mg/ml, 1.6 mg/ml to 2.8 mg/ml, 1.7 mg/ml to 2.8 mg/ml, 1.8 mg/ml to 2.8 mg/ml, 1.9 mg/ml to 2.8 mg/ml, 2.0 mg/ml to 2.8 mg/ml, 2.1 mg/ml to 2.8 mg/ml, 2.2 mg/ml to 2.8 mg/ml, 2.3 mg/ml to 2.8 mg/ml, 2.4 mg/ml to 2.8 mg/ml, 2.5 mg/ml to 2.8 mg/ml, 2.6 mg/ml to 2.8 mg/ml, 2.7 mg/ml to 2.8 mg/ml, 0.5 mg/ml to 2.7 mg/ml, 0.6 mg/ml to 2.7 mg/ml, 0.7 mg/ml to 2.7 mg/ml, 0.8 mg/ml to 2.7 mg/ml, 0.9 mg/ml to 2.7 mg/ml, 1.0 mg/ml to 2.7 mg/ml, 1.1 mg/ml to 2.7 mg/ml, 1.2 mg/ml to 2.7 mg/ml, 1.3 mg/ml to 2.7 mg/ml, 1.4 mg/ml to 2.7 mg/ml, 1.5 mg/ml to 2.7 mg/ml, 1.6 mg/ml to 2.7 mg/ml, 1.7 mg/ml to 2.7 mg/ml, 1.8 mg/ml to 2.7 mg/ml,

1.9 mg/ml to 2.7 mg/ml, 2.0 mg/ml to 2.7 mg/ml, 2.1 mg/ml to 2.7 mg/ml, 2.2 mg/ml to 2.7 mg/ml, 2.3 mg/ml to 2.7 mg/ml, 2.4 mg/ml to 2.7 mg/ml, 2.5 mg/ml to 2.7 mg/ml, 2.6 mg/ml to 2.7 mg/ml, 0.5 mg/ml to 2.6 mg/ml, 0.6 mg/ml to 2.6 mg/ml, 0.7 mg/ml to 2.6 mg/ml, 0.8 mg/ml to 2.6 mg/ml, 0.9 mg/ml to 2.6 mg/ml, 1.0 mg/ml to 2.6 mg/ml, 1.1 mg/ml to 2.6 mg/ml, 1.2 mg/ml to 2.6 mg/ml, 1.3 mg/ml to 2.6 mg/ml, 1.4 mg/ml to 2.6 mg/ml, 1.5 mg/ml to 2.6 mg/ml,

1.6 mg/ml to 2.6 mg/ml, 1.7 mg/ml to 2.6 mg/ml, 1.8 mg/ml to 2.6 mg/ml, 1.9 mg/ml to 2.6 mg/ml, 2.0 mg/ml to 2.6 mg/ml, 2.1 mg/ml to 2.6 mg/ml, 2.2 mg/ml to 2.6 mg/ml, 2.3 mg/ml to

2.6 mg/ml, 2.4 mg/ml to 2.6 mg/ml, 2.5 mg/ml to 2.6 mg/ml, 0.5 mg/ml to 2.9 mg/ml, 0.6 mg/ml to 2.5 mg/ml, 0.7 mg/ml to 2.5 mg/ml, 0.8 mg/ml to 2.5 mg/ml, 0.9 mg/ml to 2.5 mg/ml, 1.0 mg/ml to 2.5 mg/ml, 1.1 mg/ml to 2.5 mg/ml, 1.2 mg/ml to 2.5 mg/ml, 1.3 mg/ml to 2.5 mg/ml,

1.4 mg/ml to 2.5 mg/ml, 1.5 mg/ml to 2.5 mg/ml, 1.6 mg/ml to 2.5 mg/ml, 1.7 mg/ml to 2.5 mg/ml, 1.8 mg/ml to 2.5 mg/ml, 1.9 mg/ml to 2.5 mg/ml, 2.0 mg/ml to 2.5 mg/ml, 2.1 mg/ml to

2.5 mg/ml, 2.2 mg/ml to 2.5 mg/ml, 2.3 mg/ml to 2.5 mg/ml, 2.4 mg/ml to 2.5 mg/ml, 0.5 mg/ml to 2.4 mg/ml, 0.6 mg/ml to 2.4 mg/ml, 0.7 mg/ml to 2.4 mg/ml, 0.8 mg/ml to 2.4 mg/ml, 0.9 mg/ml to 2.4 mg/ml, 1.0 mg/ml to 2.4 mg/ml, 1.1 mg/ml to 2.4 mg/ml, 1.2 mg/ml to 2.4 mg/ml,

1.3 mg/ml to 2.4 mg/ml, 1.4 mg/ml to 2.4 mg/ml, 1.5 mg/ml to 2.4 mg/ml, 1.6 mg/ml to 2.4 mg/ml, 1.7 mg/ml to 2.4 mg/ml, 1.8 mg/ml to 2.4 mg/ml, 1.9 mg/ml to 2.4 mg/ml, 2.0 mg/ml to

2.4 mg/ml, 2.1 mg/ml to 2.4 mg/ml, 2.2 mg/ml to 2.4 mg/ml, 2.3 mg/ml to 2.4 mg/ml, 0.5 mg/ml to 2.3 mg/ml, 0.6 mg/ml to 2.3 mg/ml, 0.7 mg/ml to 2.3 mg/ml, 0.8 mg/ml to 2.3 mg/ml, 0.9 mg/ml to 2.3 mg/ml, 1.0 mg/ml to 2.3 mg/ml, 1.1 mg/ml to 2.3 mg/ml, 1.2 mg/ml to 2.3 mg/ml,

1.3 mg/ml to 2.3 mg/ml, 1.4 mg/ml to 2.3 mg/ml, 1.5 mg/ml to 2.3 mg/ml, 1.6 mg/ml to 2.3 mg/ml, 1.7 mg/ml to 2.3 mg/ml, 1.8 mg/ml to 2.3 mg/ml, 1.9 mg/ml to 2.3 mg/ml, 2.0 mg/ml to

2.3 mg/ml, 2.1 mg/ml to 2.3 mg/ml, 2.2 mg/ml to 2.3 mg/ml, 0.5 mg/ml to 2.2 mg/ml, 0.6 mg/ml to 2.2 mg/ml, 0.7 mg/ml to 2.2 mg/ml, 0.8 mg/ml to 2.2 mg/ml, 0.9 mg/ml to 2.2 mg/ml, 1.0 mg/ml to 2.2 mg/ml, 1.1 mg/ml to 2.2 mg/ml, 1.2 mg/ml to 2.2 mg/ml, 1.3 mg/ml to 2.2 mg/ml,

1.4 mg/ml to 2.2 mg/ml, 1.5 mg/ml to 2.2 mg/ml, 1.6 mg/ml to 2.2 mg/ml, 1.7 mg/ml to 2.2 mg/ml, 1.8 mg/ml to 2.2 mg/ml, 1.9 mg/ml to 2.2 mg/ml, 2.0 mg/ml to 2.2 mg/ml, 2.1 mg/ml to 2.2 mg/ml, 0.5 mg/ml to 2.1 mg/ml, 0.6 mg/ml to 2.1 mg/ml, 0.7 mg/ml to 2.1 mg/ml, 0.8 mg/ml to 2.1 mg/ml, 0.9 mg/ml to 2.1 mg/ml, 1.0 mg/ml to 2.1 mg/ml, 1.1 mg/ml to 2.1 mg/ml, 1.2 mg/ml to 2.1 mg/ml, 1.3 mg/ml to 2.1 mg/ml, 1.4 mg/ml to 2.1 mg/ml, 1.5 mg/ml to 2.1 mg/ml,

1.6 mg/ml to 2.1 mg/ml, 1.7 mg/ml to 2.1 mg/ml, 1.8 mg/ml to 2.1 mg/ml, 1.9 mg/ml to 2.1 mg/ml, 2.0 mg/ml to 2.1 mg/ml, 0.5 mg/ml to 2.0 mg/ml, 0.6 mg/ml to 2.0 mg/ml, 0.7 mg/ml to

2.0 mg/ml, 0.8 mg/ml to 2.0 mg/ml, 0.9 mg/ml to 2.0 mg/ml, 1.0 mg/ml to 2.0 mg/ml, 1.1 mg/ml to 2.0 mg/ml, 1.2 mg/ml to 2.0 mg/ml, 1.3 mg/ml to 2.0 mg/ml, 1.4 mg/ml to 2.0 mg/ml, 1.5 mg/ml to 2.0 mg/ml, 1.6 mg/ml to 2.0 mg/ml, 1.7 mg/ml to 2.0 mg/ml, 1.8 mg/ml to 2.0 mg/ml,

1.9 mg/ml to 2.0 mg/ml, 0.5 mg/ml to 1.9 mg/ml, 0.6 mg/ml to 1.9 mg/ml, 0.7 mg/ml to 1.9 mg/ml, 0.8 mg/ml to 1.9 mg/ml, 0.9 mg/ml to 1.9 mg/ml, 1.0 mg/ml to 1.9 mg/ml, 1.1 mg/ml to

1.9 mg/ml, 1.2 mg/ml to 1.9 mg/ml, 1.3 mg/ml to 1.9 mg/ml, 1.4 mg/ml to 1.9 mg/ml, 1.5 mg/ml to 1.9 mg/ml, 1.6 mg/ml to 1.9 mg/ml, 1.7 mg/ml to 1.9 mg/ml, 1.8 mg/ml to 1.9 mg/ml, 0.5 mg/ml to 1.8 mg/ml, 0.6 mg/ml to 1.8 mg/ml, 0.7 mg/ml to 1.8 mg/ml, 0.8 mg/ml to 1.8 mg/ml,

0.9 mg/ml to 1.8 mg/ml, 1.0 mg/ml to 1.8 mg/ml, 1.1 mg/ml to 1.8 mg/ml, 1.2 mg/ml to 1.8 mg/ml, 1.3 mg/ml to 1.8 mg/ml, 1.4 mg/ml to 1.8 mg/ml, 1.5 mg/ml to 1.8 mg/ml, 1.6 mg/ml to

1.8 mg/ml, 1.7 mg/ml to 1.8 mg/ml, 0.5 mg/ml to 1.7 mg/ml, 0.6 mg/ml to 1.7 mg/ml, 0.7 mg/ml to 1.7 mg/ml, 0.8 mg/ml to 1.7 mg/ml, 0.9 mg/ml to 1.7 mg/ml, 1.0 mg/ml to 1.7 mg/ml, 1.1 mg/ml to 1.7 mg/ml, 1.2 mg/ml to 1.7 mg/ml, 1.3 mg/ml to 1.7 mg/ml, 1.4 mg/ml to 1.7 mg/ml,

1.5 mg/ml to 1.7 mg/ml, 1.6 mg/ml to 1.7 mg/ml, 0.5 mg/ml to 1.6 mg/ml, 0.6 mg/ml to 1.6 mg/ml, 0.7 mg/ml to 1.6 mg/ml, 0.8 mg/ml to 1.6 mg/ml, 0.9 mg/ml to 1.6 mg/ml, 1.0 mg/ml to

1.6 mg/ml, 1.1 mg/ml to 1.6 mg/ml, 1.2 mg/ml to 1.6 mg/ml, 1.3 mg/ml to 1.6 mg/ml, 1.4 mg/ml to 1.6 mg/ml, 1.5 mg/ml to 1.6 mg/ml, 0.5 mg/ml to 1.5 mg/ml, 0.6 mg/ml to 1.5 mg/ml, 0.7 mg/ml to 1.5 mg/ml, 0.8 mg/ml to 1.5 mg/ml, 0.9 mg/ml to 1.5 mg/ml, 1.0 mg/ml to 1.5 mg/ml,

1.1 mg/ml to 1.5 mg/ml, 1.2 mg/ml to 1.5 mg/ml, 1.3 mg/ml to 1.5 mg/ml, 1.4 mg/ml to 1.5 mg/ml, 0.5 mg/ml to 1.4 mg/ml, 0.6 mg/ml to 1.4 mg/ml, 0.7 mg/ml to 1.4 mg/ml, 0.8 mg/ml to 1.4 mg/ml, 0.9 mg/ml to 1.4 mg/ml, 1.0 mg/ml to 1.4 mg/ml, 1.1 mg/ml to 1.4 mg/ml, 1.2 mg/ml to 1.4 mg/ml, 1.3 mg/ml to 1.4 mg/ml, 0.5 mg/ml to 1.3 mg/ml, 0.6 mg/ml to 1.3 mg/ml, 0.7 mg/ml to 1.3 mg/ml, 0.8 mg/ml to 1.3 mg/ml, 0.9 mg/ml to 1.3 mg/ml, 1.0 mg/ml to 1.3 mg/ml,

1.1 mg/ml to 1.3 mg/ml, 1.2 mg/ml to 1.3 mg/ml, 0.5 mg/ml to 1.2 mg/ml, 0.6 mg/ml to 1.2 mg/ml, 0.7 mg/ml to 1.2 mg/ml, 0.8 mg/ml to 1.2 mg/ml, 0.9 mg/ml to 1.2 mg/ml, 1.0 mg/ml to

1.2 mg/ml, 1.1 mg/ml to 1.2 mg/ml, 0.5 mg/ml to 1.1 mg/ml, 0.6 mg/ml to 1.1 mg/ml, 0.7 mg/ml to 1.1 mg/ml, 0.8 mg/ml to 1.1 mg/ml, 0.9 mg/ml to 1.1 mg/ml, 1.0 mg/ml to 1.1 mg/ml, 0.5 mg/ml to 1.0 mg/ml, 0.6 mg/ml to 1.0 mg/ml, 0.7 mg/ml to 1.0 mg/ml, 0.8 mg/ml to 1.0 mg/ml,

0.9 mg/ml to 1.0 mg/ml, 1.0 mg/ml to 1.0 mg/ml, 0.5 mg/ml to 0.9 mg/ml, 0.6 mg/ml to 0.9 mg/ml, 0.7 mg/ml to 0.9 mg/ml, 0.8 mg/ml to 0.9 mg/ml, 0.5 mg/ml to 0.8 mg/ml, 0.6 mg/ml to

0.8 mg/ml, 0.7 mg/ml to 0.8 mg/ml, 0.5 mg/ml to 0.7 mg/ml, or about 0.6 mg/ml to 0.7 mg/ml,

The docusate sodium ranges disclosed in this paragraph are hereby disclosed in combination with the medroxyprogesterone and polyethylene glycol ranges disclosed herein. Thus the docusate sodium ranges disclosed in this paragraph are hereby disclosed in combination with a medroxyprogesterone concentration of about 260 mg/ml to 440 mg/ml, 260 mg/ml to 340 mg/ml,

270 mg/ml to 330 mg/ml, 280 mg/ml to 320 mg/ml, 290 mg/ml to 310 mg/ml, 295 mg/ml to 305 mg/ml, 370 mg/ml to 430 mg/ml, 380 mg/ml to 420 mg/ml, 390 mg/ml to 410 mg/ml, or 395 mg/ml to 405 mg/ml, and optionally a polyethylene glycol concentration of about 10 mg/ml to about 40 mg/ml. For the sake of brevity, all of the combinations are not being parsed out.

[0021] By way of further example, concentrations of docusate sodium can comprise about 0.5,

0.6, 0.7, 0.8, 0.9, 1.0, 1.1 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7,

2.8, 2.9, or about 3.0 mg/ml. The docusate sodium concentrations disclosed in this paragraph are hereby disclosed in combination with the medroxyprogesterone and/or polyethylene glycol ranges disclosed herein. Thus the docusate sodium ranges disclosed in this paragraph are hereby disclosed in combination with a medroxyprogesterone concentration of about 260 mg/ml to 440

mg/ml, 260 mg/ml to 340 mg/ml, 270 mg/ml to 330 mg/ml, 280 mg/ml to 320 mg/ml, 290 mg/ml to 310 mg/ml, 295 mg/ml to 305 mg/ml, 370 mg/ml to 430 mg/ml, 380 mg/ml to 420 mg/ml, 390 mg/ml to 410 mg/ml, or 395 mg/ml to 405 mg/ml, and optionally a polyethylene glycol concentration of about 10 mg/ml to about 40 mg/ml. For the sake of brevity, all of the combinations are not being parsed out.

[0022] In preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 260 mg/ml to about 340 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 3.0 mg/ml. In further preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 260 mg/ml to about 340 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 1.0 mg/ml. In still further preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 260 mg/ml to about 340 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 0.7 mg/ml.

[0023] In other preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 270 mg/ml to about 330 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 3.0 mg/ml. In further preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 270 mg/ml to about 330 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 1.0 mg/ml. In still further preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 270 mg/ml to about 330 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 0.7 mg/ml.

[0024] In still other preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 280 mg/ml to about 320 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 3.0 mg/ml. In further preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 280 mg/ml to about 320 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 1.0 mg/ml. In still further preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 280 mg/ml to about 320 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 0.7 mg/ml.

[0025] In further preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 290 mg/ml to about 310 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 3.0 mg/ml. In further preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 290 mg/ml to about 310 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 1.0 mg/ml. In still further preferred aspects, the compositions described herein comprise medroxyprogesterone acetate at a concentration of about 290 mg/ml to about 310 mg/ml and docusate sodium at a concentration of about 0.5 mg/ml to about 0.7 mg/ml.

WHAT IS CLAIMED IS:

1. An aqueous composition for subcutaneous injection comprising medroxyprogesterone acetate at a concentration of about 260 mg/ml to 440 mg/ml, docusate sodium at a concentration of about 0.6 mg/ml to 1.5 mg/ml, and polyethylene glycol.

2. The composition according to claim 1, wherein the concentration of polyethylene glycol is about 10 mg/ml to 40 mg/ml, or about 15 mg/ml to 30 mg/ml.

3. The composition according to any one of claims 1 or 2, wherein the polyethylene glycol is polyethylene glycol 3350.

4. The composition according to any one of claims 1 to 3, further comprising a sulfate salt or a sodium salt or a sulfate salt and a sodium salt.

5. The composition according to claim 4, wherein the composition comprises a sulfate salt being sodium sulfate.

6. The composition according to any one of claims 1 to 5, further comprises a stabilizer selected from methionine, thioglycerol, monothioglycerol, lipoic acid, propyl gallate, cysteine, sodium formaldehyde sulfoxylate, or dihydrolipoic acid.

7. The composition according to any one of claims 1 to 6, further comprising a buffering salt selected from a phosphate salt or a combination of phosphate salts.

8. The composition according to claim 7, wherein the buffering salt is monobasic sodium phosphate, dibasic sodium phosphate, or a combination thereof.

9. The composition according to any one of claims 1 to 8, having a pH of about 4.0 to about 7.0, or having a pH of about 6.0 to about 7.0, or about 6.0.

10. The composition according to any one of claims 1 to 9, comprising sodium sulfate, methionine, monobasic sodium phosphate, and dibasic sodium phosphate.

11. The composition according to any one of claims 1 to 10, wherein the concentration of medroxyprogesterone acetate is about 400 mg/ml.

12. The composition according to any one of claims 1 to 10, wherein the concentration of medroxyprogesterone acetate is about 300 mg/ml.

13. The composition according to any one of claims 1 to 12, wherein the concentration of docusate sodium is about 0.6 mg/ml to about 1.3 mg/ml, about 0.6 mg/ml, about 1.0 mg/ml or about 1.3 mg ./ml.

14. The composition according to claim 13, wherein the concentration of docusate sodium is about 0.6 mg/ml.

15. The composition according to claim 13, wherein the concentration of docusate sodium is about 1.0 mg/ml.

16. The composition according to any one of claims 1 to 15, wherein the concentration of polyethylene glycol is about 20 mg/ml to about 28 mg/ml.

17. The composition according to claim 16, wherein the concentration of polyethylene glycol is about 20 mg/ml.

18. The composition according to claim 16, wherein the concentration of polyethylene glycol is about 28 mg/ml.

19. The composition according to any one of claims 1 to 18, further comprising one or more excipients selected from anhydrous sodium sulfate, L -methionine, anhydrous dibasic sodium phosphate, and anhydrous monobasic sodium phosphate, or preferably comprising all of the excipients anhydrous sodium sulfate, L -methionine, anhydrous dibasic sodium phosphate, and anhydrous monobasic sodium phosphate.

20. The composition according to any one of claims 1 to 19, wherein the composition is stable for at least 36 months under stress conditions.

21. A method for preventing pregnancy or for treating endometriosis-associated pain or endometrial carcinoma in a female subject, or treating renal carcinoma in a subject in need thereof, the method comprising subcutaneously administering to the subject a composition according to any one of claims 1-20.

22. The method according to claim 21, wherein the composition is administered once every four months to once every 6 months, or preferably once every six months.