Ophthalmic topical cream composition

Abstract

The ophthalmic therapeutic treatment composition includes a topical cream containing a crosslinked acrylic acid polymer, an acrylamide / sodium acryloyldimethyltaurate copolymer, and an effective amount of an active pharmaceutical ingredient (API) dispersed in the topical cream. The ophthalmic therapeutic treatment composition and API are formulated for topical application and treatment of various disorders such as dry eye, presbyopia, intraocular pressure, and blepharitis.

Description

[Technical field]

[0001] INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATION This application claims priority to U.S. Provisional Patent Application No. 63 / 363,356, entitled "OPHTHALMIC TOPICAL CREAM COMPOSITIONS AND METHODS," filed April 21, 2022, which is incorporated by reference herein in its entirety and for all purposes. [Background technology]

[0002] Field The present disclosure relates to ophthalmic therapeutic treatment compositions, processes, and methods of using same to treat ocular disorders and diseases, particularly by administration to the outer surface of the eyelid of a patient's eye.

[0003] explanation Eye drops are a typical means of administering ophthalmic medications to patients. For example, U.S. Pat. No. 10,610,518 discloses pilocarpine formulations and methods of administering them as eye drops. This route is simple and non-invasive, but achieves limited control over patient compliance, dosage regimen, and duration. Eye drops can lead to undesirable efficacy and clinical outcomes if subjects use them inappropriately. See Souto, EB, et al., “Advanced Formulation Approaches for Ocular Drug Delivery: State-Of-The-Art and Recent Patents”, Pharmaceutics. 2019, 11, 460: 1-29. Other ophthalmic formulations have been developed that are said to be suitable for administration by topical application to the outer surface of a subject's eyelid. See U.S. Pat. No. 9,034,830. However, there remains a need for improved ophthalmic therapeutic treatment compositions and methods. Summary of the Invention

[0004] Various embodiments provide an ophthalmic therapeutic treatment composition. In one embodiment, the ophthalmic therapeutic treatment composition comprises a topical cream comprising about 0% to about 8% (w / w) of a crosslinked acrylic acid polymer and about 0% to about 8% (w / w) of an acrylamide / sodium acryloyldimethyltaurate copolymer; and an effective amount of an active pharmaceutical ingredient (API) dispersed in the topical cream.

[0005] In some embodiments, the ophthalmic therapeutic treatment composition comprises about 0.001% to about 10% (w / w) of the API. In some embodiments, the ophthalmic therapeutic treatment composition comprises about 2% to about 8% (w / w) of the API. In some embodiments, the topical cream comprises about 2% to about 4% (w / w) of a crosslinked acrylic acid polymer. In some embodiments, the topical cream comprises about 2% to about 4% (w / w) of an acrylamide / sodium acryloyldimethyltaurate copolymer.

[0006] In some embodiments, the acrylamide / sodium acryloyldimethyltaurate copolymer is dispersed in isohexadecane combined with polysorbate 80, polysorbate 20, polysorbate 40, or polysorbate 60. In some embodiments, the API comprises pilocarpine. In some embodiments, the ophthalmic therapeutic treatment composition comprises an amount of the API that is effective for reducing dry eye symptoms and / or treating presbyopia. In some embodiments, the API comprises travoprost. In some embodiments, the ophthalmic therapeutic treatment composition comprises an amount of the API that is safe and effective for treating intraocular pressure (IOP). In some embodiments, the API comprises atropine, physostigmine, and / or donepezil. In some embodiments, the ophthalmic therapeutic treatment composition comprises an amount of the API that is safe and effective for treating myopia and blepharitis.

[0007] In some embodiments, the ophthalmic therapeutic treatment composition has a pH in the range of about 3.0 to about 7.8. In some embodiments, the pH of the ophthalmic therapeutic treatment composition is in the range of about 3.5 to about 5.5. In some embodiments, the ophthalmic therapeutic treatment composition has a viscosity in the range of about 4,000 cPs to about 400,000 cPs. In some embodiments, the viscosity of the ophthalmic therapeutic treatment composition is in the range of about 5,000 cPs to about 300,000 cPs. In some embodiments, the ophthalmic therapeutic treatment composition has a viscosity in the range of about 7,500 cPs to about 250,000 cPs.

[0008] In some embodiments, the ophthalmic therapeutic treatment composition is thixotropic. In some embodiments, the ophthalmic therapeutic treatment composition has less than about 5% (w / w) degradation of the API when measured after storage at 40° C. for 60 days after preparation of the ophthalmic therapeutic treatment composition. In some embodiments, the ophthalmic therapeutic treatment composition has less than about 10% (w / w) degradation of the API when measured after storage at 40° C. for 24 months after preparation of the ophthalmic therapeutic treatment composition.

[0009] In some embodiments, the ophthalmic therapeutic treatment composition is formulated for application to the outer surface of the eyelid to deliver the API into the eye. In some embodiments, there is less residue of the ophthalmic therapeutic treatment composition after application of the ophthalmic therapeutic treatment composition to the outer surface of the eyelid compared to application of an otherwise identical composition that includes hydroxypropylcellulose (HPC) instead of acrylamide / sodium acryloyldimethyltaurate copolymer.

[0010] Additionally, various embodiments provide a method for administering an ophthalmic medication to the eye of a patient. In one embodiment, the method comprises applying an ophthalmic therapeutic treatment composition to an exterior surface of the eyelid of the patient's eye, the ophthalmic therapeutic treatment composition comprising a topical cream comprising about 0.5% to about 8% (w / w) crosslinked acrylic acid polymer and about 0.25% to about 8% (w / w) acrylamide / sodium acryloyldimethyltaurate copolymer; and an effective amount of an active pharmaceutical ingredient (API) dispersed in the topical cream.

[0011] In some embodiments, the effective amount of the API is about 0.004% to about 10% (w / w). In some embodiments, the API comprises pilocarpine, travoprost, atropine, donepezil, or physostigmine. In some embodiments, the method comprises applying an ophthalmic therapeutic treatment composition to the outer surface of the eyelid of the patient's eye at least once per day.

[0012] In some embodiments, the method comprises applying the ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid up to four times per day. In some embodiments, applying the ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid comprises applying with an applicator. In some embodiments, the method further comprises squeezing the ophthalmic therapeutic treatment composition from a container into the applicator prior to applying the ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a bar graph summarizing findings from a residue evaluation of various ophthalmic therapeutic treatment compositions that do not contain acrylamide / sodium acryloyldimethyltaurate copolymer or SEPINEO P 600 after topical application. [Diagram 2] FIG. 2 is a bar graph summarizing findings from the emoliency evaluation of various ophthalmic therapeutic treatment compositions. [Diagram 3] FIG. 3 is a bar graph summarizing findings from the texture evaluation of various ophthalmic therapeutic treatment compositions. [Figure 4] FIG. 4 is a bar graph summarizing findings from an evaluation of residue tolerance following application of formulations containing acrylamide / sodium acryloyldimethyltaurate copolymer or SEPINEO P 600. [Diagram 5] FIG. 5 illustrates the stability of an ophthalmic therapeutic treatment composition (F2) having a pH of about 5 as a function of storage time at room temperature and at 40° C. [Figure 6]FIG. 6 illustrates the stability of an ophthalmic therapeutic treatment composition (F15) having a pH of about 3.5 as a function of storage time at room temperature and at 40° C. [Figure 7] FIG. 7 illustrates the stability of an ophthalmic therapeutic treatment composition (F23) having a pH of about 3.5 as a function of storage time at room temperature and at 40° C. [Figure 8] FIG. 8 illustrates the stability of an ophthalmic therapeutic treatment composition (F24) having a pH of about 5 as a function of storage time at room temperature and at 40° C. [Figure 9] FIG. 9 illustrates the stability of an ophthalmic therapeutic treatment composition (F27) having a pH of about 3.5 as a function of storage time at room temperature and at 40° C. [Figure 10] FIG. 10 illustrates the stability of an ophthalmic therapeutic treatment composition (F28) having a pH of about 5 as a function of storage time at room temperature and at 40° C.

[0014] Detailed Description Ophthalmic therapeutic treatment compositions have now been developed that contain a topical cream comprising about 0.0% to about 8% (w / w) crosslinked acrylic acid polymer and about 0.0% to about 8% (w / w) acrylamide / sodium acryloyldimethyltaurate copolymer, along with an effective amount of an active pharmaceutical ingredient (API) dispersed in the topical cream. In various embodiments, this polymer combination provides the ophthalmic therapeutic treatment composition with surprisingly high levels of desirable characteristics, such as low residue after application, skin emolliency, texture, and / or storage stability.

[0015] Ophthalmic treatment compositions Various embodiments include: a topical cream comprising from about 0.0% to about 8% (w / w), such as from about 0.05% to about 8% (w / w), of a crosslinked acrylic acid polymer, and from about 0.0% to about 8% (w / w), such as from 0.025% to about 8% (w / w), of an acrylamide / sodium acryloyldimethyltaurate copolymer; and An effective amount of active pharmaceutical ingredient (API) dispersed in a topical cream The present invention provides an ophthalmic therapeutic treatment composition comprising:

[0016] A variety of suitable crosslinked acrylic acid polymers are commercially available and / or may be readily synthesized by one of ordinary skill in the art. In some embodiments, the acrylic acid polymer is a homopolymer of acrylic acid. In other embodiments, the acrylic acid polymer is a homopolymer of acrylic acid and a C 10 -C 30 It is a copolymer composed primarily of acrylic acid units, with small amounts (typically <10%) of other units formed by copolymerization with compatible comonomers such as alkyl acrylates and / or methacrylic acid. Crosslinking of the acrylic acid polymer can be accomplished by various means, such as by copolymerization with crosslinking agents such as allyl sucrose or allyl pentaerythritol. In various embodiments, the crosslinked acrylic acid polymer has a molecular weight and degree of crosslinking that results in a solution viscosity (measured at 0.5 wt % and pH 7.5) in the range of about 4,000 cPs to about 80,000 cPs, such as about 40,000 cPs to about 60,000 cPs. Suitable acrylic acid polymers from commercial sources include those available from Lubrizol Corporation under the trademark CARBOPOL. In a non-limiting example, the crosslinked acrylic acid polymer is Carbomer Homopolymer Type C 980.

[0017] The amount of crosslinked acrylic acid polymer in a topical cream is typically in the range of about 0.0% to about 8% (w / w), such as about 0.05% to about 8% (w / w), such as about 0.5% to about 8% (w / w), about 2% to about 6% (w / w), about 2% to about 4% (w / w), or about 3% to about 5% (w / w). The amount of crosslinked acrylic acid polymer can be adjusted based on viscosity. For example, for a crosslinked acrylic acid polymer having a viscosity in the range of about 40,000 cPs to about 60,000 cPs, a suitable amount can be in the range of about 3% to about 5% (w / w). Those skilled in the art will understand the relationship between viscosity and concentration such that a higher viscosity crosslinked acrylic acid polymer can be used in a smaller amount, while a larger amount of a lower viscosity polymer may be appropriate in some embodiments.

[0018] Various acrylamide / sodium acryloyldimethyltaurate copolymers are commercially available and / or can be easily synthesized by one skilled in the art. In some embodiments, the acrylamide / sodium acryloyldimethyltaurate copolymer is a copolymer of acrylamide and sodium acryloyldimethyltaurate. In other embodiments, the acrylamide / sodium acryloyldimethyltaurate copolymer may contain small amounts (typically <10%) of other units formed by copolymerization of acrylamide and sodium acryloyldimethyltaurate with compatible comonomers such as methacrylamide and / or sodium methacryloyldimethyltaurate.

[0019] The amount of acrylamide / sodium acryloyldimethyltaurate copolymer in a topical cream is typically in the range of about 0.0% to about 8% (w / w), such as 0.025% to about 8% (w / w), such as 0.25% to about 8% (w / w), about 2% to about 6% (w / w), about 2% to about 4% (w / w), or about 3% to about 5% (w / w). The amount of acrylamide / sodium acryloyldimethyltaurate copolymer can be adjusted based on viscosity, similar to that discussed above with respect to the crosslinked acrylic acid polymer.

[0020] Similarly, the type, amount, and viscosity of the polymeric components (e.g., crosslinked acrylic acid polymers and acrylamide / sodium acryloyldimethyltaurate copolymers) can be adjusted or selected to impart the desired rheological properties (e.g., viscosity and / or thixotropy) to the ophthalmic therapeutic treatment composition. In one embodiment, the ophthalmic therapeutic treatment composition has a viscosity in the range of about 4,000 cPs to about 400,000 cPs, such as about 5,000 cPs to about 300,000 cPs or about 7,500 cPs to about 250,000 cPs.

[0021] In one embodiment, the ophthalmic therapeutic treatment composition is formulated for application to the outer surface of the eyelid to deliver API into the eye. The ophthalmic therapeutic treatment composition can be surprisingly formulated to be thixotropic. Such a high degree of thixotropy is desirable from the standpoint of patient compliance, since the lower the viscosity during flow, the easier it is to push the ophthalmic therapeutic treatment composition from the container into the applicator before applying the ophthalmic therapeutic treatment composition to the outer surface of the eyelid of the patient's eye. After such application, the higher viscosity provided by the ophthalmic therapeutic treatment composition after application to the eyelid allows it to stay in place, thereby providing the subject additional time before being rubbed into the eye.

[0022] Acrylamide / sodium acryloyldimethyl taurate copolymers are typically provided by commercial sources in the form of emulsion gels. See, for example, G. Bonacucina, et al., "Characterization and Stability of Emulsion Gels Based on Acrylamide / Sodium Acryloyldimethyl Taurate Copolymer" AAPS PharmSciTech. 2009 Jun; 10(2): 368-375. In a non-limiting example, acrylamide / sodium acryloyldimethyl taurate copolymer is SEPINEO P 600, available from Seppic, an Air Liquide Healthcare subsidiary, in the form of a concentrated dispersion in isohexadecane combined with polysorbate 80.

[0023] In various embodiments, the crosslinked acrylic acid polymer and the acrylamide / sodium acryloyldimethyltaurate copolymer are combined to form a topical cream. In addition to common ingredients such as water, topical creams may contain small amounts of other ingredients that are useful for manufacturing and / or formulation. Non-limiting examples include oils such as mineral oil and polyoxyl castor oil, glycols such as propylene glycol and polyethylene glycol, alcohols such as sorbitol and cetyl alcohol, parabens such as methylparaben and propylparaben, stabilizers such as edetate disodium, salts such as magnesium chloride, pH adjusters such as citric acid and sodium hydroxide, etc. Suitable amounts of such minor formulation ingredients are illustrated by the non-limiting examples in Table 1.

[0024] [Table 1]

[0025] Surprisingly, in some embodiments, the combination of crosslinked acrylic acid polymer and acrylamide / sodium acryloyldimethyltaurate copolymer provides unexpectedly high levels of one or more desirable properties that enhance patient tolerance and thus promote patient compliance. For example, Figure 1 illustrates a bar graph summarizing findings from residue evaluation of various ophthalmic therapeutic treatment compositions after topical application. Table 2 summarizes the major components and pH of the formulations.

[0026] [Table 2]

[0027] As shown in Table 2, formulations 1-18 are free of acrylamide / sodium acryloyldimethyltaurate copolymer or SEPINEO P 600. Additionally, formulations 5-11 and 15-18 are free of hydroxypropylcellulose (HPC). The data summarized in Figure 1 show that topical application of formulations containing a combination of crosslinked acrylic acid polymer (Carbomer) and hydroxypropylcellulose (HPC) to the skin of test subjects resulted in the perception of undesirable levels of residue on the skin. Similar trends were observed in the evaluation of emolliency (Figure 2) and texture (Figure 3).

[0028] In contrast, when the combination with crosslinked acrylic acid polymer contains acrylamide / sodium acryloyldimethyl taurate copolymer instead of HPC, the test subjects report a surprisingly higher level of satisfaction with the level of residue on the skin, the emolliency, and / or the texture. The data summarized in FIG. 4 show that topical application of various formulations containing the combination of crosslinked acrylic acid polymer and acrylamide / sodium acryloyldimethyl taurate copolymer to the skin of the test subjects resulted in the perception of a much more desirable level of residue on the skin compared to HPC (see FIG. 1). Similarly, a better evaluation of emolliency and texture is observed for the formulation containing the combination of crosslinked acrylic acid polymer and acrylamide / sodium acryloyldimethyl taurate copolymer. Table 3 summarizes the main ingredients and pH of the formulations shown in FIG. 4.

[0029] In various embodiments, the ophthalmic therapeutic treatment composition has a pH in the range of about 3.0 to about 7.8, such as in the range of about 3 to about 5.5, about 3 to about 5, about 3.5 to about 5.5, or about 3.5 to about 5. In one embodiment, the pH is less than 5, such as in the range of about 3.0 to less than 5 or about 3.5 to less than 5. For example, in one embodiment, the pH is in the range of about 3.5 to about 4.5. In another embodiment, the pH is in the range of about 3.5 to about 4.

[0030] Surprisingly, in some embodiments, the combination of crosslinked acrylic acid polymer and acrylamide / sodium acryloyldimethyltaurate copolymer provides an unexpectedly high level of physical stability and API chemical stability, especially when stored at a pH below 5. In various embodiments, the degradation of the ophthalmic therapeutic treatment composition is measured at 40° C. or at room temperature. Room temperature is a temperature in the range of about 15° C. to about 25° C. In some embodiments, room temperature is 25° C. The degradation may be accelerated at 40° C. compared to the degradation at room temperature. For example, FIG. 5 illustrates the chemical stability of an ophthalmic therapeutic treatment composition (F2) having a pH of about 5 as a function of storage time at room temperature and 40° C. The illustrated impurities are degradation products of pilocarpine. In contrast, FIG. 6 illustrates the significantly improved stability data for another ophthalmic therapeutic treatment composition (F15) at pH 3.5 instead of pH 5. A similar trend was observed in the evaluation of the ophthalmic therapeutic treatment composition at pH 3.5 (F23) (Figure 7) compared to an otherwise identical formulation at pH 5 (F24) (Figure 8). Similarly, the stability data for the ophthalmic therapeutic treatment composition at pH 3.5 (F27) (Figure 9) is significantly improved compared to an otherwise identical formulation at pH 5 (F28) (Figure 10). Table 3 summarizes the major components and pH of the formulations. The amounts shown are based on the weight percent of the indicated components.

[0031] [Table 3]

[0032] In various embodiments, the ophthalmic treatment composition has less than about 5% (w / w) degradation of the API when measured after storage at 40° C. for 60 days after preparation of the ophthalmic treatment composition. In some embodiments, the ophthalmic treatment composition has less than about 4.5% (w / w) degradation of the API when measured after storage at 40° C. for 60 days after preparation of the ophthalmic treatment composition. In some embodiments, the ophthalmic treatment composition has less than about 4% (w / w) degradation of the API when measured after storage at 40° C. for 30 days after preparation of the ophthalmic treatment composition. In one embodiment, the ophthalmic treatment composition has less than about 10% (w / w) degradation of the API when measured after storage at 40° C. for 4 months after preparation of the ophthalmic treatment composition.

[0033] The ophthalmic therapeutic treatment composition comprises an effective amount of an active pharmaceutical ingredient (API) dispersed in a topical cream. In one embodiment, the ophthalmic therapeutic treatment composition comprises about 0.001% to about 10% (w / w) of the API. In some embodiments, the API comprises pilocarpine, travoprost, atropine, donepezil, physostigmine, or a combination thereof. In some embodiments, the API can be pilocarpine, travoprost, atropine, donepezil, physostigmine, or a combination thereof. For example, in one embodiment, the ophthalmic therapeutic treatment composition comprises about 0.004% to about 10% (w / w), about 1% to about 8% (w / w), or about 2% to about 8% (w / w) of the API. For any particular API, the effective amount in the composition can be adjusted based on the disease or disorder for which treatment is indicated. For example, in one embodiment, the API is pilocarpine, and the effective amount is typically in the range of about 1% to about 8% (w / w). In one embodiment, the ophthalmic therapeutic treatment composition comprises an API (e.g., pilocarpine) in an amount effective to relieve symptoms of dry eye. In one embodiment, the ophthalmic therapeutic treatment composition comprises an API (e.g., pilocarpine) in an amount effective to treat presbyopia. In one embodiment, the API comprises travoprost. In one embodiment, the ophthalmic therapeutic treatment composition comprises an API (e.g., travoprost) in an amount effective to treat intraocular pressure (IOP). In one embodiment, the API comprises physostigmine. In one embodiment, the ophthalmic therapeutic treatment composition comprises an API (e.g., physostigmine) in an amount effective to treat blepharitis. In one embodiment, the API comprises donepezil. In one embodiment, the ophthalmic therapeutic treatment composition comprises an API (e.g., donepezil) in an amount effective to treat blepharitis.

[0034] The ophthalmic therapeutic treatment composition disclosed herein can be prepared in various ways, for example, by thoroughly mixing the various components to form a topical cream. In one embodiment, the acrylamide / sodium acryloyldimethyltaurate copolymer is added to the other component and mixed thoroughly before adding the crosslinked acrylic acid polymer. When EDTA is present in the formulation, it has been found that mixing in reverse order (i.e., adding the crosslinked acrylic acid polymer first, then the acrylamide / sodium acryloyldimethyltaurate copolymer) results in the formation of EDTA crystallites. In another embodiment, when a strong base (such as NaOH) is used to adjust the pH of the ophthalmic therapeutic treatment composition, the strong base is added to the other component and mixed thoroughly before adding the API. It has been found that adding in reverse order (i.e., adding the API first, then adding the strong base to the other component) results in a higher level of API degradation.

[0035] In various embodiments, the ophthalmic therapeutic treatment composition is sterilized. For example, in one embodiment, the ophthalmic therapeutic treatment composition is sterilized by e-beam processing. As shown by the data in Table 4, such e-beam sterilization tended to increase the viscosity of the ophthalmic therapeutic treatment composition somewhat, but the viscosity still remained within the desired range.

[0036] [Table 4]

[0037] Treatment Method Various embodiments provide methods of treating an ocular disease or disorder by topical administration of the ophthalmic therapeutic treatment compositions described herein.

[0038] For example, one embodiment provides a method for administering an ophthalmic medication to the eye of a patient, the method comprising applying an ophthalmic therapeutic treatment composition to an exterior surface of the eyelid of the patient's eye, the ophthalmic therapeutic treatment composition comprising a topical cream comprising about 0.5% to about 8% (w / w) crosslinked acrylic acid polymer and about 0.25% to about 8% (w / w) acrylamide / sodium acryloyldimethyltaurate copolymer; and an effective amount of an active pharmaceutical ingredient (API) dispersed in the topical cream. The amounts and types of the various ingredients, as well as indications, are described above with respect to the ophthalmic therapeutic treatment composition.

[0039] In various embodiments, the API is pilocarpine and the method of treatment is effective in alleviating symptoms of dry eye. In another embodiment, the API is pilocarpine and the method of treatment is effective in treating presbyopia. In one embodiment, the API comprises travoprost and the method of treatment is effective in treating intraocular pressure (IOP). In one embodiment, the API comprises physostigmine or donepezil and the method of treatment is effective in treating blepharitis. In one embodiment, the API comprises travoprost or pilocarpine and the method of treatment is effective in treating blepharitis.

[0040] In one embodiment, the method includes applying an ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid by applying with an applicator. For example, in one embodiment, the treatment includes forcing the ophthalmic therapeutic treatment composition from a container into an applicator (such as a tube attached to the container), and then applying the ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid using the applicator, for example, by further pushing the container to force the ophthalmic therapeutic treatment composition out of the applicator and onto the eyelid.

[0041] In various embodiments, the method of treatment comprises applying the ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid at least once per day. For example, in one embodiment, the method comprises applying the ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid up to four times per day, such as once per day, twice per day, three times per day, or four times per day.

[0042] Moreover, although the foregoing has been described in some detail by way of illustration and example for purposes of clarity and understanding, it will be understood by those skilled in the art that numerous and various modifications may be made without departing from the essence of the present disclosure. It should therefore be clearly understood that the forms disclosed herein are merely illustrative and are not intended to limit the scope of the present disclosure, but rather to cover all modifications and alternatives that fall within the true scope and essence of the present disclosure.

[0043] Exemplary embodiments 1. A topical cream comprising about 0.0% to about 8% (w / w) of a crosslinked acrylic acid polymer and about 0.0% to about 8% (w / w) of an acrylamide / sodium acryloyldimethyltaurate copolymer; and Dispersed in the topical cream is an effective amount of an active pharmaceutical ingredient (API). 13. An ophthalmic therapeutic treatment composition comprising: 2. The ophthalmic therapeutic treatment composition of embodiment 1, wherein the ophthalmic therapeutic treatment composition comprises from about 0.001% to about 10% (w / w) of the API. 3. The ophthalmic therapeutic treatment composition of embodiment 2, wherein the ophthalmic therapeutic treatment composition comprises about 2% to about 8% (w / w) of the API. 4. The ophthalmic therapeutic treatment composition of any one of embodiments 1 to 3, wherein the topical cream comprises about 2% to about 4% (w / w) of a crosslinked acrylic acid polymer. 5. The ophthalmic therapeutic treatment composition of any one of embodiments 1-4, wherein the topical cream comprises about 2% to about 4% (w / w) of acrylamide / sodium acryloyldimethyltaurate copolymer. 6. The ophthalmic therapeutic treatment composition of any one of embodiments 1-5, wherein the acrylamide / sodium acryloyldimethyltaurate copolymer is dispersed in isohexadecane combined with polysorbate 80. 7. The ophthalmic therapeutic treatment composition of any one of embodiments 1-6, wherein the API comprises pilocarpine. 8. The ophthalmic therapeutic treatment composition of embodiment 7, wherein the ophthalmic therapeutic treatment composition comprises an amount of API that is effective to relieve symptoms of dry eye and / or treat presbyopia. 9. The ophthalmic therapeutic treatment composition according to any one of embodiments 1-6, wherein the API comprises travoprost. 10. The ophthalmic therapeutic treatment composition of embodiment 9, wherein the ophthalmic therapeutic treatment composition comprises an amount of API that is effective to treat intraocular pressure (IOP). 11. The ophthalmic therapeutic treatment composition according to any one of embodiments 1-6, wherein the API comprises physostigmine and / or donepezil. 12. The ophthalmic therapeutic treatment composition of embodiment 11, wherein the ophthalmic therapeutic treatment composition comprises an amount of API that is effective to treat blepharitis. 13. The ophthalmic therapeutic treatment composition according to any one of embodiments 1 to 12, wherein the ophthalmic therapeutic treatment composition has a pH within the range of about 3.0 to about 7.8. 14. The ophthalmic therapeutic treatment composition of embodiment 13, wherein the pH of the ophthalmic therapeutic treatment composition is within the range of about 3.5 to about 5.5. 15. The ophthalmic therapeutic treatment composition of any one of embodiments 1-14, wherein the ophthalmic therapeutic treatment composition has a viscosity in the range of about 4,000 cPs to about 400,000 cPs. 16. The ophthalmic therapeutic treatment composition of embodiment 15, wherein the viscosity of the ophthalmic therapeutic treatment composition is in the range of about 5,000 cPs to about 300,000 cPs. 17. The ophthalmic therapeutic treatment composition of any one of embodiments 1-11, wherein the ophthalmic therapeutic treatment composition has a viscosity in the range of about 7,500 cPs to about 250,000 cPs. 18. The ophthalmic therapeutic treatment composition according to any one of embodiments 1 to 17, wherein the ophthalmic therapeutic treatment composition is thixotropic. 19. The ophthalmic therapeutic treatment composition of any one of embodiments 1-18, wherein the ophthalmic therapeutic treatment composition has less than about 5% (w / w) degradation of the API when measured after storage at 40° C. for 60 days after preparation of the ophthalmic therapeutic treatment composition. 20. The ophthalmic therapeutic treatment composition of any one of embodiments 1-19, wherein the ophthalmic therapeutic treatment composition has less than about 10% (w / w) degradation of the API when measured after storage at 40° C. for 4 months after preparation of the ophthalmic therapeutic treatment composition. 21. The ophthalmic therapeutic treatment composition of any one of embodiments 1-20, wherein the ophthalmic therapeutic treatment composition is formulated for application to the exterior of the eyelid to deliver an API into the eye. 22. The ophthalmic therapeutic treatment composition of embodiment 21, wherein there is less residue of the ophthalmic therapeutic treatment composition following application of the composition to the outer surface of the eyelid, as compared to application of an otherwise identical composition comprising hydroxypropylcellulose (HPC) instead of acrylamide / sodium acryloyldimethyltaurate copolymer. 23. A method for administering an ophthalmic medication to an eye of a patient, said method comprising applying an ophthalmic therapeutic treatment composition to an exterior surface of an eyelid of the patient's eye; The ophthalmic therapeutic treatment composition comprises a topical cream comprising about 0.5% to about 8% (w / w) of a crosslinked acrylic acid polymer and about 0.25% to about 8% (w / w) of an acrylamide / sodium acryloyldimethyltaurate copolymer; and an effective amount of an active pharmaceutical ingredient (API) dispersed in the topical cream. method. 24. The method of embodiment 23, wherein the effective amount of the API is from about 0.001% to about 10% (w / w). 25. The method of embodiment 23 or 24, wherein the API comprises pilocarpine, travoprost, atropine, donepezil, or physostigmine. 26. The method of any one of embodiments 23-25, wherein the method comprises applying an ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid at least once per day. 27. The method of embodiment 26, wherein the method comprises applying the ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid up to four times per day. 28. The method of any one of embodiments 23-27, wherein applying the ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid comprises applying with an applicator. 29. The method of embodiment 28, wherein the method further comprises forcing the ophthalmic therapeutic treatment composition from a container into an applicator prior to applying the ophthalmic therapeutic treatment composition to the outer surface of the patient's eyelid.

Claims

1. A topical cream comprising 0.05% to 8% (w / w) of a crosslinked acrylic acid polymer and 0.025% to 8% (w / w) of an acrylamide / sodium acryloyldimethyltaurate copolymer; and 0.001% to 10% (w / w) of active pharmaceutical ingredients (APIs) dispersed in the aforementioned topical cream. A treatment composition for ophthalmic therapy, including [the specified ingredient].

2. The ophthalmic treatment composition according to claim 1, wherein the ophthalmic treatment composition contains 2% to 8% (w / w) of API.

3. The ophthalmic treatment composition according to claim 1 or 2, wherein the topical cream contains 2% to 4% (w / w) of a cross-linked acrylic acid polymer.

4. The ophthalmic treatment composition according to claim 1 or 2, wherein the topical cream comprises 2% to 4% (w / w) of acrylamide / sodium acryloyldimethyltaurate copolymer.

5. An ophthalmic treatment composition according to claim 1 or 2, wherein an acrylamide / sodium acryloyldimethyltaurate copolymer is dispersed in isohexadecane combined with polysorbate 80.

6. An ophthalmic treatment composition according to claim 1 or 2, wherein the API comprises pilocarpine.

7. The ophthalmic treatment composition according to claim 6, wherein the ophthalmic treatment composition contains an amount of API that is effective in alleviating the symptoms of dry eye and / or treating presbyopia.

8. An ophthalmic treatment composition according to claim 1 or 2, wherein the API comprises travoprost.

9. The ophthalmic treatment composition according to claim 8, wherein the ophthalmic treatment composition contains an amount of API effective for treating intraocular pressure (IOP).

10. The ophthalmic treatment composition according to claim 1 or 2, wherein the API comprises physostigmine and / or donepezil.

11. The ophthalmic treatment composition according to claim 10, wherein the ophthalmic treatment composition contains an amount of API effective for treating blepharitis.

12. The ophthalmic treatment composition according to claim 1 or 2, wherein the ophthalmic treatment composition has a pH in the range of 3.0 to 7.

8.

13. The ophthalmic treatment composition according to claim 12, wherein the pH of the ophthalmic treatment composition is in the range of 3.5 to 5.

5.

14. The ophthalmic treatment composition according to claim 1 or 2, wherein the ophthalmic treatment composition has a viscosity in the range of 4,000 cPs to 400,000 cPs.

15. The ophthalmic treatment composition according to claim 1 or 2, wherein the ophthalmic treatment composition has a viscosity in the range of 7,500 cPs to 250,000 cPs.

16. The ophthalmic treatment composition according to claim 1 or 2, wherein the ophthalmic treatment composition is thixotropic.

17. An ophthalmic treatment composition according to claim 1 or 2, wherein, when measured after storage at 40°C for 60 days after preparation, the ophthalmic treatment composition has a degradation of less than 5% (w / w) of API.

18. The ophthalmic treatment composition according to claim 1 or 2, wherein the ophthalmic treatment composition is formulated for application to the outer surface of the eyelid for delivery of an API into the eye.

19. The ophthalmic treatment composition according to claim 18, wherein, compared to the application of a composition otherwise identical, comprising hydroxypropyl cellulose (HPC) instead of acrylamide / sodium acryloyldimethyltaurate copolymer, the residue of the ophthalmic treatment composition after application to the outer surface of the eyelid is less.

20. A method for administering an ophthalmic drug to a patient's eye, the method comprising applying an ophthalmic treatment composition to the outer surface of the eyelid of the patient's eye, The ophthalmic treatment composition comprises a topical cream containing 0.5% to 8% (w / w) of crosslinked acrylic acid polymer and 0.25% to 8% (w / w) of acrylamide / sodium acryloyldimethyltaurate copolymer; and a topical cream containing 0.001% to 10% (w / w) of an active pharmaceutical ingredient (API) dispersed in the topical cream. method.

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