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Title:
SELF-SOLIDIFYING TOPICAL FORMULATIONS WITH LOCAL ANESTHETIC
Document Type and Number:
WIPO Patent Application WO/2021/101777
Kind Code:
A1
Abstract:
A self-solidifying topical formulation can include from 6 wt% to 8 wt% lidocaine, from 6 wt% to 8 wt% tetracaine, from about 0.5 wt% to about 15 wt% film-forming suspension agent, film-forming filler having a solubility in water of at least 30% at 25°C based on weight, and from about 25 wt% to about 75 wt% water.

Inventors:
ZHANG JIE (US)
Application Number:
PCT/US2020/060095
Publication Date:
May 27, 2021
Filing Date:
November 12, 2020
Export Citation:
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Assignee:
ZHANG JIE (US)
International Classes:
A61K47/10; A61K31/167; A61K47/36; A61K47/40; A61L31/08; A61L31/14; A61P23/02
Foreign References:
US20170296484A12017-10-19
US9693976B22017-07-04
US8741332B22014-06-03
US20030072731A12003-04-17
Attorney, Agent or Firm:
OAKESON, Gary P. (US)
Download PDF:
Claims:
CLAIMS What Is Claimed Is: 1. A self-solidifying topical formulation, comprising: from 6 wt% to 8 wt% lidocaine; from 6 wt% to 8 wt% tetracaine; from about 0.5 wt% to about 15 wt% film-forming suspension agent; film-forming filler having a solubility in water of at least 30% at 25°C based on weight; and from about 25 wt% to about 75 wt% water. 2. The self-solidifying topical formulation of claim 1, wherein the lidocaine and the tetracaine are present collectively in the self-solidifying topical formulation as a eutectic mixture. 3. The self-solidifying topical formulation of claim 1, wherein the lidocaine and the tetracaine are present at about a 1:1 weight ratio. 4. The self-solidifying topical formulation of claim 1, wherein the film-forming suspension agent includes xanthan gum, hydroxyethyl cellulose, polyvinyl pyrrolidone, polyacrylic acid, or a combination thereof. 5. The self-solidifying topical formulation of claim 1, wherein the film-forming suspension agent includes from about 0.5 wt% to about 7 wt% of the xanthan gum based on a total weight of the self-solidifying topical formulation. 6. The self-solidifying topical formulation of claim 1, wherein the film-forming filler includes from about 2 wt% to about 50 wt% of the maltodextrin based on a total weight of the self-solidifying topical formulation.

7. The self-solidifying topical formulation of claim 1, wherein the film-forming filler includes from about 4 wt% to about 50 wt% of the maltodextrin and from about 1 wt% to about 30 wt% of the gum Arabic, based on a total weight of the self- solidifying topical formulation. 8. The self-solidifying topical formulation of claim 1, wherein the film-forming filler includes maltodextrin, gum Arabic, or a combination thereof. 9. The self-solidifying topical formulation of claim 1, wherein the film-forming filler is present at from about 2 wt% to about 65 wt%. 10. The self-solidifying topical formulation of claim 1, wherein the film-forming filler is present at from about 8 wt% to about 65 wt%. 11. The self-solidifying topical formulation of claim 1, wherein a weight ratio of the film-forming filler to the water is from about 1:3 to about 2:1. 12. The self-solidifying topical formulation of claim 1, wherein a weight ratio of the film-forming filler to the water is from about 1:2 to about 3:2. 13. The self-solidifying topical formulation of claim 1, wherein a weight ratio of the film-forming filler to the water is from about 5:6 to about 3:2. 14. The self-solidifying topical formulation of claim 1, wherein the water is present in the self-solidifying topical formulation at from about 30 wt% to about 65 wt%.

15. The self-solidifying topical formulation of claim 1, further comprising from about 2 wt% to about 15 wt% polyvinyl alcohol based on a total weight of the self- solidifying topical formulation. 16. The self-solidifying topical formulation of claim 15, wherein the polyvinyl alcohol is present in the self-solidifying topical formulation at from 4 wt% to about 14 wt%. 17. The self-solidifying topical formulation of claim 1, further comprising a C2- C4 alcohol co-solvent. 18. The self-solidifying topical formulation of claim 17, wherein the C2-C4 alcohol co-solvent is a monoalcohol selected from ethanol, n-propanol, isopropanol, n-butanol, iso-butanol, tert-butanol, or a combination thereof. 19. The self-solidifying topical formulation of claim 17, wherein the C2-C4 alcohol co-solvent is present in the self-solidifying topical formulation at from about 0.1 wt% to about 15 wt%. 20. The self-solidifying topical formulation of claim 1, wherein the formulation further comprises from about 2 wt% to about 15 wt% softening agent. 21. The self-solidifying topical formulation of claim 18, wherein the softening agent includes, petrolatum, white petrolatum, lanolin, mineral oil, dimethicone, glycerol, or a combination thereof. 22. The self-solidifying topical formulation of claim 1, wherein after application to an intact and undamaged skin surface to form an application layer having a thickness of 0.5 mm, wherein the application layer forms a non-tacky surface most distal to the skin surface within 60 minutes of the application under ambient exposure conditions at a temperature of 25 ºC and relative humidity of 70%. 23. A self-solidifying topical formulation, comprising: from 6 wt% to 8 wt% lidocaine; from 6 wt% to 8 wt% tetracaine; from about 0.5 wt% to about 3 wt% xanthan gum; film forming filler selected from maltodextrin, gum Arabic, or a combination thereof; from about 2 wt% to 15 wt% polyvinyl alcohol, and from about 30 wt% to about 60 wt% water. 24. The self-solidifying topical formulation of claim 23, wherein the lidocaine and tetracaine are in the form of eutectic mixture. 25. The self-solidifying topical formulation of claim 23, further comprising from 0.1 wt% to about 15 wt% of a C2-C4 alcohol co-solvent. 26. The self-solidifying topical formulation of claim 23, wherein the film- forming filler is present at from about 2 wt% to about 65 wt%. 27. The self-solidifying topical formulation of claim 23, wherein the film- forming filler is present at from about 8 wt% to about 65 wt%. 28. A method for treating a skin surface for anesthesia or analgesia, comprising: applying an application layer of any one of the self-solidifying topical formulations of claims 1-27 on a skin surface; delivering the local anesthetic through the skin surface; allowing the formulation layer to dry sufficiently to form a solidified formulation layer; and removing the solidified formulation layer from the skin surface. 29. The method of claim 28, wherein a time interval from applying the application layer to removing the solidified application layer ranges from 15 minutes to 4 hours. 30. The method of claim 28, wherein a time interval from applying the application layer to removing the solidified application layer ranges from 20 minutes to 2 hours. 31. The method of claim 28, wherein a thickness of the formulation layer ranges from 0.05 mm to 4 mm. 32. The method of claim 28, wherein a thickness of the formulation layer ranges from 0.1 mm to 1 mm. 33. The method of claim 28, wherein treating the skin surface occurs prior to a medical or cosmetic procedure. 34. The method of claim 28, wherein the removing includes peeling the solidified application layer off the skin surface. 35. A method of making a self-solidifying topical formulation, comprising combining a local anesthetic mixture of lidocaine and tetracaine with a film-forming suspension agent and a film-forming filler to form the self-solidifying topical formulation, the self-solidifying topical formulation comprising: from 6 wt% to 8 wt% lidocaine; from 6 wt% to 8 wt% tetracaine; from about 0.5 wt% to about 15 wt% film-forming suspension agent; film-forming filler having a solubility in water of at least 30% at 25°C based on weight; and from about 25 wt% to about 75 wt% water. 36. The method of claim 35, further comprising combining polyvinyl alcohol and water to dissolve the polyvinyl alcohol in the water to form a polyvinyl alcohol solution, and combining the polyvinyl alcohol solution with the local anesthetic, the film-forming suspension agent, and the film-forming filler. 37. The method of claim 35, further comprising combing the lidocaine and the tetracaine to form the mixture results in a eutectic mixture of the lidocaine and the tetracaine. 38. The method of claim 35, further comprising combining a paraben anti- microbial agent with a C2-C4 alcohol to form a paraben alcohol solution, and combining the paraben alcohol solution with the local anesthetic, the film-forming suspension agent, and the film-forming filler. 39. The method of claim 35, wherein the film-forming suspension agent includes xanthan gum. 40. The method of claim 35, wherein the film-forming filler includes maltodextrin. 41. The method of claim 35, wherein the film-forming filler is present at from about 2 wt% to about 65 wt%. 42. The method of claim 35, wherein the film-forming filler is present at from about 8 wt% to about 65 wt%.

Description:
SELF-SOLIDIFYING TOPICAL FORMULATIONS WITH LOCAL ANESTHETIC BACKGROUND Compositions for topical application can be useful in treating medical conditions and/or preparing for medical or cosmetic procedures. Topical semi-solid or viscous fluid formulations (pastes, lotions, gels, creams, etc.) and patches containing active agents can be used to treat conditions of the upper skin layers and can allow for transdermal administration of the active agents to local tissue underlying the skin. DETAILED DESCRIPTION Local anesthetics can be incorporated into semi-solid formulations, e.g., creams, which can be used to anesthetize human skin. In some instances, local anesthetic formulations may be in the form of a semi-solid formulation that is self- solidifying, where upon evaporation of water and/or other co-solvent that may be present, forms a solidified layer that forms from an initially applied semi-solid formulation. In some examples of the present disclosure, when applying to human skin, there may be multiple types of properties that can be advantageous. For example, the formulation can solidify into a soft (not rigid) and coherent (strength to stay as one piece) layer. In some examples, the layer can be easily lifted off the human skin surface with no or little residue on the skin surface, which avoids having to wipe the formulation off the skin and clean the skin. Furthermore, the local anesthetic can be included so that it is not fully dissolved in the formulation, e.g., some droplets or particles partially exist as solid particles or oil droplets, such as is the case with eutectic mixtures of local anesthetics. The formulation can also keep the solid particles or oil droplets evenly distributed (suspended) in the formulation. In some examples, if the formulation comprises tetracaine which is subject to hydrolytic degradation (degrades when in contact with water), the formulation may be formulated to not contain too much water. For example, the higher the water to tetracaine weight ratio, the faster the degradation rate (degradation rate can be defined in terms of percentage of tetracaine in the formulation degraded per unit time). As the formulations contain a certain concentration of tetracaine, the ratio of water to tetracaine can be kept low using highly water-soluble film-forming filler, for example. The self-solidifying topical formulations and method of the present disclosure can deliver an amount of local anesthetic to a skin surface and the underlying tissue. The self-solidifying topical formulation can be applied as a semi-solid to form a thin formulation layer, e.g., 0.05 mm to 4 mm, and can then convert to a solidified formulation layer following evaporation of a portion of the water and/or co-solvent therefrom. The solidified formulation layer can be soft (not rigid) and coherent (having the structural stability to remain in a single piece). The solidified formulation layer can be removed from a skin surface either by peeling or washing therefrom, for example. In some examples, the solidified formulation layer does not retain its semi- solid properties that existed when initially applied to a skin surface, depending on if it dries enough to convert from the semi-solid formulation to the solidified formulation. The self-solidifying topical formulations and method of the present disclosure can deliver an amount of local anesthetic to a skin surface and the underlying tissue. The self-solidifying topical formulation can be applied as a semi-solid to form a thin formulation layer, e.g., 0.05 mm to 4 mm, and can then convert to a solidified formulation layer following evaporation of a portion of the water and/or co-solvent therefrom. The solidified formulation layer can be soft (not rigid) and coherent (having the structural stability to remain in a single piece). The solidified formulation layer can be removed from a skin surface either by peeling or washing therefrom, for example. In some examples, the solidified formulation layer does not retain its semi- solid properties that existed when initially applied to a skin surface, depending on if it dries enough to convert from the semi-solid formulation to the solidified formulation. In accordance with examples herein, a self-solidifying topical formulation can include from about 6% to 8% lidocaine and from about 6% to 8% tetracaine, from about 0.5 wt% to about 15 wt% film-forming suspension agent, film-forming filler having a solubility in water of at least 30% at 25°C based on weight, and from about 25 wt% to about 75 wt% water. In one example, the local anesthetic can be in the form of a eutectic mixture of lidocaine and tetracaine. The film-forming suspension agent can be xanthan gum, hydroxyethyl cellulose, polyvinyl pyrrolidone, polyacrylic acid, or a combination thereof. For example, the film-forming suspension agent can be xanthan gum present at from about 0.5 wt% to about 7 wt% based on a total weight of the topical formulation. In another example, the film-forming filler can be from about 2 wt% to about 50 wt% of the maltodextrin based on a total weight of the topical formulation. In another example, the film-forming filler can include both about 4 wt% to about 50 wt% of the maltodextrin and from about 1 wt% to about 30 wt% of the gum Arabic, based on a total weight of the topical formulation. In one specific example, the film-forming suspension agent can be, for example, xanthan gum and the film-forming filler can be, for example, maltodextrin. In further detail, the film- forming filler can be present at from about 2 wt% to about 65 wt%, or from about 8 wt% to about 65 wt%. Though not always the case, the film-forming filler and the water can be present at a weight ratio from about 1:3 to about 2:1, for example, or at a weight ratio of the film-forming filler to the water is from about 1:2 to about 3:2, or from about 5:6 to about 3:2. The water can be present in the topical formulation at from about 30 wt% to about 65 wt%. In some examples, from about 2 wt% to about 15 wt% polyvinyl alcohol can be included, or at from about 4 wt% to about 14 wt%, based on a total weight of the topical formulation. In still additional examples, the formulation can include C2-C4 alcohol co-solvent. In one example, the C2-C4 alcohol co-solvent can be a monoalcohol, such as ethanol, n-propanol, isopropanol, n-butanol, iso-butanol, tert-butanol, or a combination thereof. The C2-C4 alcohol co- solvent can be present in the topical formulation at from about 0.1 wt% to about 15 wt%, for example. In some examples, the formulation can further include from about 2 wt% to about 15 wt% softening agent, e.g., petrolatum, white petrolatum, lanolin, mineral oil, dimethicone, glycerol, or a combination thereof. After application to an intact and undamaged skin surface to form an application layer having a thickness of 0.5 mm, the application layer can be formulated to form a non-tacky surface most distal to the skin surface within 60 minutes of the application under ambient exposure conditions at a temperature of 25 ºC and relative humidity of 70%. In another more specific example, a self-solidifying topical formulation can include from 6 wt% to 8 wt% lidocaine and from 6 wt% to 8 wt% tetracaine; from about 0.5 wt% to about 3 wt% xanthan gum; from about 15 wt% to about 50 wt% maltodextrin, gum Arabic, or a combination thereof; from about 2 wt% to 15 wt% polyvinyl alcohol, and from about 30 wt% to about 60 wt% water. The lidocaine and the tetracaine can be in the form of a eutectic mixture, for example. In one example, the formulation can include from 0.1 wt% to about 15 wt% of a C2-C4 alcohol co- solvent. In another example, a method for treating a skin surface for anesthesia or analgesia can include applying an application layer of any one of the previous topical formulations, delivering the local anesthetic through the skin surface, allowing the formulation layer to dry sufficiently to form a solidified formulation layer, and removing the solidified formulation layer from the skin surface. In one example, a time interval from applying the application layer to removing the solidified application layer can be from about 15 minutes to about 4 hours, or from about 20 minutes to about 2 hours. A thickness of the formulation layer, as applied, can be from about 0.05 mm to about 4 mm, or from about 0.1 mm to about 1 mm. Treating the skin surface can occur prior to a medical or cosmetic procedure. Removal can be, after solidification, by peeling the solidified application layer off the skin surface. In another example, removal can be by washing. In another example, a method of making a self-solidifying topical formulation can include combining a local anesthetic mixture of lidocaine and tetracaine with a film-forming suspension agent and a film-forming filler to form the self-solidifying topical formulation. The self-solidifying topical formulation can include from 6 wt% to 8 wt% lidocaine, from 6 wt% to 8 wt% tetracaine, from about 0.5 wt% to about 15 wt% film-forming suspension agent, from about 8 wt% to about 65 wt% film-forming filler having a solubility in water of at least 30% at 25°C based on weight, and from about 25 wt% to about 75 wt% water. In some examples, the method can include combining polyvinyl alcohol and water to dissolve the polyvinyl alcohol in the water to form a polyvinyl alcohol solution, and combining the polyvinyl alcohol solution with the local anesthetic, the film-forming suspension agent, and the film-forming filler. In another example, the method can include combing lidocaine and tetracaine to form a eutectic mixture of the lidocaine and the tetracaine. The method can likewise further include combining a paraben anti-microbial agent with a C2-C4 alcohol to form a paraben alcohol solution, and combining the paraben alcohol solution with the local anesthetic, the film-forming suspension agent, and the film-forming filler. In one example, the film-forming suspension agent includes xanthan gum. In another example, the film-forming filler includes maltodextrin. As an initial matter, when discussing the self-solidifying topical formulations, or method of treating a skin surface, the various discussions can be considered applicable to each of these examples, whether or not they are explicitly discussed in the context of that example. Thus, for example, in discussing a local anesthetic in the context of the self-solidifying topical formulation, such discussions are also relevant to the method of treating a skin surface herein, and vice versa. Self-solidifying Topical Formulations with Lidocaine and Tetracaine As mentioned, a self-solidifying topical formulation can include from 6 wt% to 8 wt% lidocaine; from 6 wt% to 8 wt% tetracaine; from about 0.5 wt% to about 15 wt% film-forming suspension agent, e.g., xanthan gum, hydroxyethyl cellulose, polyvinyl pyrrolidone, polyacrylic acid, or a combination thereof; from about 8 wt% to about 65 wt% film-forming filler, e.g., maltodextrin, gum Arabic, or a combination thereof; and from about 25 wt% to about 75 wt% water. In this example, the film- forming filler can have a solubility in water of at least 30% at 25 C based on weight. In a more specific example, a self-solidifying topical formulation can include from about 0.5 wt% to about 3 wt% xanthan gum; from about 20 wt% to about 50 wt% maltodextrin, gum Arabic, or a combination thereof; from about 2 wt% to 15 wt% polyvinyl alcohol; and from about 30 wt% to about 60 wt% water. These self-solidifying topical formulations herein can be applied to skin surfaces for purposes of anesthesia or analgesia. As used herein, the term “anesthesia” or the like refers to the prevention of pain expected to occur, such as in connection with a painful procedure. For example, the self-solidifying topical formulations herein can be applied to anesthetize a skin surface and proximate tissues before a medical or cosmetic procedure, e.g., cutting the skin, needle prick, laser procedure, injection, etc. On the other hand, the terms “Analgesia,” “analgesic,” or the like refer to reducing or eliminating an existing pain, and include a deprivation or lessening of feeling or awareness relative to existing pain. For example, the self- solidifying topical formulations can be used at a site of a post-hepatic neuralgia. The self-solidifying topical formulations described herein can be in the form of semi-solid formulations (pastes, gels, creams, and the like) which can be applied to a skin surface. The self-solidifying topical formulation can have a viscosity such that the self-solidifying topical formulation does not run or roll off the skin surface upon application, while not viscous to the point that would prohibit the spreading of the formulation on the skin to form a thin layer. As used herein, the term “semi-solid” can refer to a composition with the viscosity similar to that of typical pharmaceutical creams, for example, having a viscosity of about 10,000 centipoise (cP) to about 2,000,000 cP, from about 25,000 cP to about 2,000,000 cP, about 40,000 cP to about 800,000 cP, from about 60,000 cP to about 600,000 cP, from about 200,000 cP to 1,000,000 cP, or from about 200,000 cP to about 500,000 cP. Self-solidifying topical formulations having viscosities in this range that can be deemed semi-solids can include creams, ointments, pastes, viscous lotions, gels, and the like. For clarity, semi-solid formulations are not the same as peels or peelable layers that can be formed from semi-solid formulation applied to the skin followed by evaporation or removal of solvent and/or co-solvent therefrom. The self-solidifying topical formulations herein can be formulated to be applied as a formulation layer on a skin surface. In some examples, after application to a skin surface as a formulation layer having a thickness ranging from about 0.05 mm to about 4 mm, the formulation layer can form a non-tacky surface most distal to the skin surface within 60 minutes, or in some cases within 30 minutes, of the application when applied to an intact and undamaged skin exposed to an ambient temperature of 25 ºC and a relative humidity of 70% or below. For a more specific example, after application to an intact and undamaged skin surface to form an application layer having a thickness of 0.5 mm, the application layer can form a non- tacky surface most distal to the skin surface within 60 minutes of the application under ambient exposure conditions at a temperature of 25 ºC and relative humidity of 70%. In another example, under the same conditions, after application to a skin surface as a formulation layer at a thickness of about 1 mm, a non-tacky surface most distal to the skin surface can likewise be formed within 30 minutes. When solidified, the formulation layer can be referred to as a “solidified formulation layer,” which indicates that the semi-solid formulation applied as a formulation layer has converted from a semi-solid, e.g., cream, into a soft, coherent solid that can be removed from the skin as a cohesive solid, e.g., peeled away from the skin. Lidocaine and Tetracaine As previously indicated, the self-solidifying topical formulations can include from about 6 wt% to about 8 wt% lidocaine and from about 6 wt% to about 8 wt% tetracaine. For example, the lidocaine and the tetracaine can be local anesthetics at a weight ratio of about 3:4 to about 4:3, about 4:5 to about 5:4, or at about 1:1. In one example, the local anesthetics can include from about 6 wt% to about 8 wt% lidocaine and from about 6 wt% to about 8 wt% tetracaine, based on a total weight of the topical formulation. The local anesthetic can be in the form of a eutectic mixture, for example. The local anesthetics can be fully dissolved or partially dissolved in the self- solidifying topical formulation. In some examples, the local anesthetics in the formulation can include solid particles or oil droplets. A film-forming suspension agent can permit even distribution of the solid particles or oil droplets in the self- solidifying topical formulation, which can contribute to proper dosage of local anesthetic when the self-solidifying topical formulation is applied to a skin surface. Film-forming Suspension Agents The topical formulations, presented herein, can include from about 0.2 wt% to about 20 wt% film-forming suspension agent. In other examples, the film-forming suspension agent can range from about 0.5 wt% to about 12 wt%, from about 1 wt% to about 7 wt%, or from about 1.5 wt% to about 3 wt%, based on a total weight of the topical formulation. Multiple film-forming suspension agents may be present, which may fall within these ranges in aggregate. For clarity, polyvinyl alcohol is not a film- forming suspension agent as described herein, though it can be included as a separate film-former elasticizing polymer, for example. Polyvinyl alcohol alone does not act enough to adequately suspend eutectic mixture of lidocaine and tetracaine in a formulation, but can provide additional elasticity to the solidified formulation. The film-forming suspension agent can include xanthan gum, hydroxyethyl cellulose, polyvinyl pyrrolidone, polyacrylic acid, or a combination thereof. In an example, the film-forming suspension agent can include xanthan gum. In one example, the xanthan gum can be present at from about 0.5 wt% to about 7 wt%, from about 1 wt% to about 4 wt%, or at from about 1.5 wt% to about 3 wt%, for example. The film-forming suspension agent can suspend or distribute un-dissolved solid particles or oil droplets of local anesthetic in the self-solidifying topical formulation, for example. The ability to suspend or distribute un-dissolved solid particles or oil droplets of local anesthetic in the self-solidifying topical formulation can prevent agglomeration of a local anesthetic. Furthermore, these suspension agents are also film-formers, in that they contribute to film formation and become part of the polymer matrix of the solidified formulation layer that is ultimately formed after water and/or co-solvent evaporation or removal. In other words, the film- forming suspension agent can also act as a film-former and can thereby contribute to a cohesiveness of the solidified formulation layer. Furthermore, a suspension agent that is also a film former offers the added benefit of helping the aforementioned solidification of the formulation layer applied to a skin surface. Film-forming Fillers Topical formulations comprising local anesthetic agent for anesthetizing intact human skin often is formulated with a significant amount of water to achieve desired anesthesia onset time. However, ester-type local anesthetic agents, such as tetracaine, can be subject to hydrolytic degradation, making them unstable in some water-based formulations. The higher the water to ester-type local anesthetic agent ratio in the formulation, the faster the hydrolytic degradation rate (“degradation rate” is defined as percentage of the ester-type local anesthetic degraded in a unit time). These two otherwise conflicting formulation ingredients can be used together and have good shelf-life by controlling the water to ester-type local anesthetic weight ratio. Furthermore, by using ester-type local anesthetics, fast skin anesthesia onset time (shorter than 45-60 minutes for normal intact non-facial human skin) may be achieved. To reduce the concentration of water in the formulation, filler can be used to reduce the water content, and thus, reduce the ratio of water to ester-type local anesthetic, thus, providing for a more stable ester-type local anesthetic in the topical formulations described herein. In accordance with this, certain film-forming fillers can be used that not only contribute to the film formation of the topical formation, but also do not significantly impact the viscosity of the topical formulation. Furthermore, the film-forming filler can be “highly water soluble,” defined herein to be at least 30 wt% soluble in water at 25 ºC, and in some examples, do not increase the viscosity of the formulations as much as other common film-forming fillers, e.g., polyvinyl alcohol. Maltodextrin and gum Arabic are two of those highly water soluble fillers. To illustrate, certain film-forming fillers with high water solubility can be good fillers because they do not tend to be separated from the rest of the formulation, especially when they also contribute to film formation. In some examples, the film-forming filler can be selected so that when it is present in water at a 1:4 weight ratio (or 20 wt% film-forming filler), the viscosity of the resulting solution is no higher than 100,000 centipoise (cP), or no higher than 50,000 cP, for example. In particular, two different types of film formers are examples of such film-forming fillers, namely maltodextrin and gum Arabic. These particular film-forming fillers provide good properties as a filler and as a film former, as they have minimal effect in increasing the formulation viscosity, even when used at very high concentrations (for example, 30 wt% or higher). In comparison, even 20 wt% polyvinyl alcohol or xanthan gum, which could make the topical formulation too viscous for application to a skin surface. The self-solidifying topical formulation can further include a film-forming filler. The film-forming filler can be present, for example, at from about 2 wt% to about 65 wt%, from about 8 wt% to about 65 wt%, from about 4 wt% to about 50 wt%, from about 15 wt% to about 50 wt%, from 20 wt% to about 40 wt%, or from about 20 wt% to about 30 wt%. As mentioned, these film-forming fillers can be, for example, highly water-soluble. In the context of the film-forming fillers, the term “highly water-soluble” indicates a fully soluble solute of the film-forming filler in water (w/w) when the solute is present at 30 wt% or greater (25°C). Examples of film-forming fillers that are also highly water-soluble can include maltodextrin, gum Arabic, or a combination thereof. In some examples, the film- forming filler can include maltodextrin. In another example, the film-forming filler can include maltodextrin and gum Arabic. When multiple film-forming fillers are present, the film-forming fillers can be present at the same amount or at differing amounts relative to one another, but the aggregate weight percentage in the formulation with within the 2 wt% to 65 wt% range, the 8 wt% to 65 wt% range, or other ranges cited previously, or subranges thereof. For example, maltodextrin can be present at from about 2 wt% to about 50 wt% and gum Arabic can be present at from about 1 wt% to about 30 wt% in one example, provided the total film-forming filler is no greater than 65 wt%. Solvents The topical formulation can include from about 25 wt% to about 75 wt% water, for example, as the only solvent, or in some examples, as a major solvent with other co-solvent present. In other examples, water can be present in the formulation from about 30 wt% to about 65 wt% or from about 35 wt% to about 50 wt%, prior to skin application. Upon application a portion of the water in the formulation can evaporate. Evaporation of water from an application layer can contribute to solidification of the formulation layer. Appropriate concentration of water in the formulation, as described previously, can help achieve fast onset of anesthetic or analgesic effect. In some examples, the topical formulation can have an anesthetic or analgesic effect within about 30 minutes, or within about 45 minutes of application. When the local anesthetic in the formulation includes an ester type local anesthetic, such as tetracaine, water can hydrolytically degrade the local anesthetic. The higher an amount of water in the formulation, the faster a rate of hydrolytic degradation. Incorporating a high concentration of filler, such as film-forming filler, for example, in the formulation can reduce the amount of water in the formulation and thus improve the stability of the ester-type local anesthetic agent in the formulation. In some examples, a weight ratio of film-forming filler to water can be from about 1:3 to about 2:1, from about 1:2 to about 3:2, or from about 5:6 to about 3:2. In some examples, an amount of the film-forming filler in the formulation can be about the same or greater than an amount of water in the formulation. In other examples, such as when the film-forming filler is present at lower concentrations, e.g, less than about 15 wt%, less than about 12 wt%, or less than about 8 wt%, these film-forming filler to water weight ratios may not be present. However, the presence of the film-forming filler may still allow for a reduction in the concentration of water in the formulation in accordance with the present disclosure. In other examples, an amount of water in the formulation can be offset by including a co-solvent. Thus, in some examples, the self-solidifying topical formulations can include other solvents, such as co-solvents including C2-C4 alcohols. In some examples, the C2-C4 alcohol can be a monoalcohol selected from ethanol, n-propanol, isopropanol, n-butanol, iso-butanol, tert-butanol, or a combination thereof. In other examples, polyols can be included, such as lower alkyl (C2-C4) diols or triols. In one example, the co-solvent can be included in the topical formulation at from about 0.1 wt% to about 25 wt%, or from about 3 wt% to about 15 wt%. In one example, the co-solvent can include ethanol. Polyvinyl Alcohol In some examples, the self-solidifying topical formulation layer can be formulated to solidify into a soft, coherent solid layer. The addition of certain other film formers can contribute to this. For example a film-forming elasticizing polymer, such as polyvinyl alcohol, can be included in addition to the film-forming filler and the film-forming suspension agent. In one example, polyvinyl alcohol can be added to provide coherence and additional elasticity, and in some instances, to further assist with the solidification of the formulation layer, once applied and allowed to dry for a period of time. When present, the polyvinyl alcohol can be included at from about 2 wt% to about 15 wt%. In yet other examples, the polyvinyl alcohol can be present at from about 4 wt% to about 14 wt% or from about 6 wt% to about 12 wt%. In further detail, if included, the polyvinyl alcohol can be dissolved in an aqueous phase of formulation. However, polyvinyl alcohol can cross-link during refrigeration and may result in premature solidification of the self-solidifying topical formulation. Thus, in order to avoid this, the amount of polyvinyl alcohol can be limited to some degree in favor of higher concentrations of the film-forming filler, such as maltodextrin and/or gum Arabic that do not increase the viscosity as much as polyvinyl alcohol, for example. In further detail, in accordance with examples of the present disclosure, the polyvinyl alcohol can have a weight average molecular weight from about 20,000 Mw to about 200,000 Mw, from about 30,000 Mw to about 100,000 Mw, or from about 30,000 to about 80,000 Mw. Additives In some examples, the topical formulation can further include various additives. Additives can be added to impart a physical or chemical property on the topical formulation. Example additives can include a softening agent, an antimicrobial agent, a pH adjusting agent, or a combination thereof. In one example, an additive can be a softening agent which can prevent the solidified formulation layer from becoming too rigid, which may otherwise contribute to cracking, lack of comfort on the skin, etc. The softening agent can be present in the topical formulation at from about 3 wt% to about 25 wt% or from about 6 wt% to about 15 wt%. Example softening agents can include, petrolatum, white petrolatum, lanolin, mineral oil, dimethicone, glycerol, or a combination thereof. In an example, the softening agent can include white petrolatum. In another example, an additive can include an antimicrobial agent. An antimicrobial agent can be present in the topical formulation at from about 0.01 wt% to about 1 wt% of an antimicrobial agent. The antimicrobial agent can include any compound suitable to inhibit the growth of harmful microorganisms. Antimicrobial agents can include biocides, fungicides, and the like. In one example, the antimicrobial agent can include methyl paraben, propyl paraben, potassium sorbate, or a combination thereof. Methods of Treating Skin Surfaces In further detail, a method of treating a skin surface for anesthesia and/or analgesia. In one example, a method of treating a skin surface for achieving anesthesia or analgesia can include applying a formulation layer of a self-solidifying topical formulation (as described elsewhere herein) onto a skin surface. The method can further include delivering local anesthetic (within the formulation layer) through the skin surface, allowing the formulation layer to dry sufficiently to form a solidified formulation layer, and removing the solidified formulation layer from the skin surface. The application formulation layer can be applied at an average thickness that can range from about 0.05 mm to about 4 mm, from about 0.1 mm to about 2 mm, from about 0.3 mm to about 1.5 mm, or from about 0.5 mm to about 1 mm. Upon application of the formulation layer, the formulation layer can become solidified. The formulation can be self-solidifying. As used herein, "self-solidifying" indicates that the formulation does not require any assistance to solidify as a soft- solid and have a non-tacky surface most distal to a skin surface that the formulation is applied thereto. Conversion from a semi-solid formulation layer to a solidified formulation layer can occur by the evaporation of water and/or other co-solvents that may be present, for example. Upon application to a skin surface at a formulation layer having a thickness from 0.05 mm to 4 mm, the local anesthetic of the self-solidifying topical formulation can be delivered through the skin surface. In an example, the formulation layer at the thickness of 0.5 mm can form a non-tacky surface most distal to the skin surface within 60 minutes, within 45 minutes, or within 30 minutes of the application when applied to intact and undamaged skin and exposed to an ambient temperature of 25 ºC and a relative humidity of 70% or below. Delivery of the local anesthetic can continue through the skin surface for the duration of the application period. In one example, the application period can range from 30 minutes to 4 hours, 20 minutes to 2 hours, or from 30 minutes to 90 minutes. Upon completion of the treatment, the solidified formulation layer can be removed from the skin surface. The removal of the solidified formulation layer can occur by peeling the solidified formulation layer off a skin surface. In another example, the removal of the solidified formulation layer can occur by washing the solidified formulation layer off the skin surface. Definitions It is to be understood that this disclosure is not limited to the particular process steps and materials disclosed herein because such process steps and materials may vary somewhat. It is also to be understood that the terminology used herein is used for the purpose of describing particular examples only. The terms are not intended to be limiting because the scope of the present disclosure is intended to be limited only by the appended claims and equivalents thereof. It is be noted that, as used in this specification and the appended claims, the singular forms ”a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. “Skin” is defined to include skin of mammals, including human skin in any form, including intact, diseased, ulcerous, or broken skin. The term “intact and undamaged” skin or skin surface refers to living skin that resides on the body of its host mammal organism, i.e. intact, and further is not damaged in any way, e.g., with cuts, scrapes, surgical incisions, open wounds, skin sores, skin diseases, etc. Intact and undamaged skin is considered to be normal skin on a mammal in its normal condition. In one example, the intact and undamaged skin is the skin of a human subject. As used herein, "film-former" or “film-forming” refers to various component that can be included in the self-solidifying topical formulations that convert from a solubilized or dispersed component in the semi-solid self-solidifying topical formulations described herein to contribute to and become part of a cohesive film that forms, e.g., that may be peelable, when solvent and/or co-solvent is evaporated therefrom. All weight percentages herein are based on a total weight of the self- solidifying topical formulation prior to skin application, unless indicated otherwise. As used herein, a plurality of active agents, compounds, solvents, and/or materials may be presented in a common list for convenience. However, these lists should be construed as though each member of the list is individually identified as a separate and unique member. Thus, no individual member of such list should be construed as a de facto equivalent of any other member of the same list solely based on their presentation in a common group without indications to the contrary. Concentrations, amounts, and other numerical data may be expressed or presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and thus should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. As an illustration, a numerical range of “about 1 to about 5” should be interpreted to include not only the explicitly recited values of about 1 to about 5, but also include individual values and sub-ranges within the indicated range. Thus, included in this numerical range are individual values such as 2, 3, and 4 and sub-ranges such as from 1-3, from 2-4, and from 3-5, etc. Additionally, a numerical range with a lower end of “0” can include a sub-range using “0.1” as the lower end point. EXAMPLES The following illustrate examples of the present disclosure. However, it is to be understood that the following are only exemplary or illustrative of the application of principles of the present disclosure. Numerous modifications and alternative compositions, systems, and methods may be devised by those skilled in the art without departing from the spirit and scope of the present disclosure. The appended claims are intended to cover such modifications and arrangements. Thus, while the above has been described with some particularity, the following provides further example details. Example 1 – Preparation of Topical Formulations Topical formulations A-O (Formulations A-O) are prepared in accordance with Tables 1-4, as follows: Table 1 Topical Formulations A D I ngredient Type Formulation ID A B C D Formulations A and D are prepared by admixing hydroxyethyl cellulose (Formulation D) or xanthan gum (Formulation A) with a eutectic mixture of 1:1 (wt:wt) lidocaine and tetracaine (an oily substance). A polyvinyl alcohol in water solution (pre-prepared with appropriate heating and mixing) is then added, followed by rigorous stirring with the eutectic mixture. Maltodextrin is then added, followed by more rigorous stir. Formulations B and C are prepared by admixing xanthan gum, white petrolatum, methyl paraben and propyl paraben in ethanol solution, and a eutectic mixture of lidocaine and tetracaine. A pre-prepared polyvinyl alcohol in water solution is then added to the above mixture followed by rigorous stir. Maltodextrin (Formulation B) or Gum Arabic (Formulation C) is then admixed therein, followed by rigorous stir. Both formulations form a fine white paste. Several additional formulations may also be prepared similarly in accordance with examples of the present disclosure, provided in Tables 2-4 below. The preparation methods are similar to those utilized in preparing Formulations B and C as described previously. Table 2 – Topical Formulations E-H I ngredient Type Formulation ID E F G H I ngredient Type Formulation ID I J K L Table 4 – Topical Formulations M-O I ngredient Type Formulation ID M N O Example 2 - Solidification of Topical Formulations on Skin Surfaces To evaluate the solidification properties of the topical formulations that can be prepared in accordance with the present disclosure, Formulations A, B, F, and J were prepared and selected for further study. Formulations A, B, F, and J were respectively applied as a 0.5 mm thick layer of the fine white paste on a skin surface on the back of an individual's hand. After about 30 minutes, a layer of each of the formulation solidified into a coherent soft solid and was not tacky to the touch. In addition, the skin covered by each of the solidified application layer was numb, or anesthetized. The solidified application layer was peeled off the skin surface following treatment and did not leave behind any residue.