Emulsion type suppository practical for vaginal administration

Abstract

The invention discloses an emulsion type suppository practical for vaginal administration, and relates to the technical field of pharmaceutical preparations, the suppository is a solid at room temperature, and can be converted into a cream type preparation in situ under vaginal temperature and wetting conditions; the suppository is composed of active and pharmaceutically acceptable auxiliary materials, the auxiliary materials comprise structural lipid, an emulsifier, a gel matrix and a pH regulator, and a suppository body is softened at body temperature and mixed with body fluid to form a cream mixture easy to coat on the mucous membrane surface in situ. The transformation process avoids greasy feeling and local discomfort possibly brought by a traditional greasy suppository, and also eliminates the trouble that the prefabricated cream needs to be matched with a special administration device, so that the local medication experience of a patient is improved while the administration convenience is ensured. Besides, through reasonable selection of auxiliary materials, the cream formed through conversion can provide proper adhesion, and the retention time of the medicine at the action part can be prolonged.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical preparations, in particular to a cream-type suppository for vaginal administration. BACKGROUND

[0002] A vaginal suppository is a classic solid preparation for external use, which usually maintains a solid state at room temperature, and is designed to rapidly soften, melt or dissolve at body temperature after being inserted into the vaginal cavity by fingers or a device, so as to release the carried drug at the action site for local or systemic treatment.

[0003] The existing conventional suppository, especially the type with oil as the base, has the advantages of convenient administration and good stability, but in the use process, it often causes discomfort to the patient due to incomplete melting, greasy feeling or leakage, affecting the medication compliance. On the other hand, the cream-type preparation such as vaginal cream has good tissue compatibility and is easy to spread, but its preparation process is relatively complex, and it usually needs to be used with a disposable applicator, increasing the cost and the use steps.

[0004] In view of the above technical problems, a new type of vaginal suppository is designed, which not only retains the stability and convenience of traditional suppositories in storage and transportation, but also can be converted into a cream-like form with better affinity under in-vivo conditions, thereby improving the local drug experience of the patient, thereby solving the above technical problems. SUMMARY

[0005] In view of the deficiencies of the prior art, the present application provides a cream-type suppository for vaginal administration, which solves the technical problems proposed in the background art.

[0006] To achieve the above purpose, the present application is implemented by the following technical scheme: a cream-type suppository for vaginal administration, which is solid at room temperature and can be converted into a cream-like preparation in situ under the temperature and wet conditions of the vagina; the suppository is composed of active and pharmaceutically acceptable excipients, and the excipients include structural lipids, emulsifiers, gel bases and pH regulators.

[0007] Preferably, the composition of the suppository includes, based on the total weight of the suppository: 0.001% to 20% of active ingredients; 10% to 50% of structural lipids; 2% to 15% of emulsifiers; 0.1% to 5% of gel bases; 0.1% to 3% of pH regulators; and the balance is other pharmaceutically acceptable carriers.

[0008] Preferably, the structural lipids are selected from one or more combinations of hydrogenated coconut glyceride, cetylstearyl alcohol, glycerin monostearate and glycerin distearate.

[0009] Preferably, the emulsifier is a non-ionic surfactant, preferably one or more of PEG-20 glyceryl stearate, polysorbate 80, sucrose fatty acid ester, poloxamer.

[0010] Preferably, the gel base is one or more of sodium carbomer, carbomer 934, hypromellose, sodium alginate.

[0011] Preferably, the pH regulator is a buffer pair of organic acid and its salt, preferably a combination of lactic acid and calcium lactate, and the suppository forms a cream in the vagina with a pH of 3.5-5.5, preferably 4.0-5.0.

[0012] Preferably, the active ingredient is selected from an estrogen, a progestogen, an antibacterial, an antifungal or an antiviral; preferably, the estrogen is estradiol, estriol, estradiol valerate or progestin; the progestogen is progesterone.

[0013] Preferably, the active ingredient and its amount are as follows: each suppository contains 10 mg of progestin, and the total weight of the suppository is 2-4 g; each suppository contains 12.5 μg of estradiol, and the total weight of the suppository is 2-4 g; each suppository contains 1 mg of estradiol valerate, and the total weight of the suppository is 2-4 g; each suppository contains 400 mg of progesterone, and the total weight of the suppository is 2-4 g.

[0014] Preferably, the suppository completely melts into a uniform cream in simulated vaginal fluid at 37°C within 30 minutes.

[0015] Preferably, the method comprises the following steps: (1) heating and melting the structural lipid and the emulsifier to form an oil phase; (2) dispersing the gel base and the pH regulator in purified water and stirring until uniform to form an aqueous phase; (3) slowly adding the aqueous phase to the oil phase while stirring, maintaining the temperature and homogenizing to obtain a uniform emulsion; (4) adding the active ingredient to the emulsion obtained in step (3) and stirring until uniform; (5) pouring the drug-containing emulsion obtained in step (4) into a suppository mold, cooling, solidifying, and demolding to obtain the temperature-sensitive vaginal cream suppository.

[0016] Advantages The present application provides a kind of emulsion type suppository for vaginal administration, the present application combines the solid form of suppository with the local application characteristics of emulsion.In preparation and circulation link, its solid characteristics enable it to maintain physical stability at room temperature, like traditional suppository, without complex emulsification process and special cold chain transportation.In use link, when placed in vagina, the suppository softens at body temperature and mixes with body fluid, forming a cream-like mixture in situ, which is easy to spread on the mucosal surface.This transformation process avoids the greasy feeling and local discomfort that may be caused by traditional oil suppositories, and eliminates the trouble of preformed cream requiring a special applicator, thereby ensuring the convenience of administration while improving the local drug experience of patients.In addition, by reasonable selection of excipients, the cream formed by the transformation can provide appropriate adhesion, which helps to prolong the retention time of the drug at the action site. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 A flowchart schematic diagram of the emulsion type suppository for vaginal administration according to the present application. DETAILED DESCRIPTION

[0018] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0019] Please refer to Figure 1 The present application provides a technical solution: an emulsion type suppository for vaginal administration, which is solid at room temperature and can be transformed into a cream-like preparation in situ under vaginal temperature and wet conditions; the suppository is composed of active and pharmaceutically acceptable excipients, and the excipients include structural lipids, emulsifiers, gel matrix and pH regulators.

[0020] The present embodiment is further provided to include, based on the total weight of the suppository: 0.001% to 20% of active ingredients; 10% to 50% of structural lipids; 2% to 15% of emulsifiers; 0.1% to 5% of gel matrix; 0.1% to 3% of pH regulators; and the balance is other pharmaceutically acceptable carriers.

[0021] The present embodiment is further provided to be selected from one or more combinations of hydrogenated coconut glyceride, cetylstearyl alcohol, glycerin monostearate and glycerin distearate.

[0022] In this embodiment, the emulsifier is further configured to be a nonionic surfactant, preferably one or more selected from PEG-20 glyceryl stearate, polysorbate 80, sucrose fatty acid ester, and poloxamer.

[0023] In this embodiment, the gel matrix is ​​further configured to be one or more of sodium carbomer, carbomer 934, hydroxypropyl methylcellulose, and sodium alginate.

[0024] In this embodiment, the pH adjuster is a buffer pair composed of organic acids and their salts, preferably a combination of lactic acid and calcium lactate, and the pH value of the cream formed by the conversion of the suppository in the vagina is 3.5-5.5, preferably 4.0-5.0.

[0025] In this embodiment, the active ingredient is further selected from estrogen, progesterone, antibacterial drugs, antifungal drugs, or antiviral drugs; preferably, the estrogen is estradiol, estriol, estradiol valerate, or proestrene; and the progesterone is progesterone.

[0026] In this embodiment, the active ingredient and its dosage are further configured to be any of the following specifications: each suppository contains 10 mg of proestradiol, and the total weight of the suppository is 2-4 g; each suppository contains 12.5 μg of estradiol, and the total weight of the suppository is 2-4 g; each suppository contains 1 mg of estradiol valerate, and the total weight of the suppository is 2-4 g; each suppository contains 400 mg of progesterone, and the total weight of the suppository is 2-4 g.

[0027] In this embodiment, the suppository is further configured such that it completely melts into a uniform cream within 30 minutes in simulated vaginal fluid at 37°C.

[0028] This embodiment is further configured to include the following steps: (1) heating and melting structural lipids and emulsifiers to form an oil phase; (2) dispersing gel matrix and pH adjuster in purified water and stirring evenly to form an aqueous phase; (3) slowly adding the aqueous phase to the oil phase under stirring, maintaining the temperature and homogenizing to obtain a uniform emulsion; (4) adding the active ingredient to the emulsion obtained in step (3) and stirring evenly; (5) pouring the drug-containing emulsion obtained in step (4) into a suppository mold, cooling, solidifying, and demolding to obtain the temperature-sensitive vaginal suppository.

[0029] Its detailed connection method is a well-known technology in this field. The following mainly introduces the working principle and process, and the specific work is as follows.

[0030] Example: This example aims to prepare a vaginal suppository containing proestrene as the active ingredient. In practice, the prescribed amounts of excipients were first accurately weighed, including hydrogenated coconut oil glyceride and cetearyl alcohol as structural lipids, PEG-20 stearate glyceride as an emulsifier, sodium carbomer as a gel matrix, and lactic acid and calcium lactate as pH adjusters. The preparation process adopted a hot-melt method: hydrogenated coconut oil glyceride, cetearyl alcohol, and PEG-20 stearate glyceride were heated together to approximately 70-75°C, stirred until completely melted and mixed uniformly to form an oil phase. At the same time, sodium carbomer was slowly dispersed in an appropriate amount of purified water, followed by the addition of lactic acid and calcium lactate, and stirred until a homogeneous aqueous gel was formed. Under continuous stirring, the aqueous phase was slowly added to the oil phase maintained at the same temperature, and moderate homogenization was performed using mechanical stirring to obtain a uniform milky white proemulsion. Once the mixture has cooled to approximately 50°C, near its freezing point but still in a fluid state, the pre-sieved proestrene raw material is added and stirred until fully dispersed. Subsequently, this drug-containing semi-fluid mixture is metered into vaginal suppository molds pre-coated with a release agent. After standing and cooling at room temperature until completely solidified, the suppository is demolded to obtain the finished suppository product. The final suppository is a smooth solid that, at body temperature, can fuse with vaginal fluid, transforming into an easily spreadable cream-like form, thus facilitating drug release and absorption.

[0031] It should be noted that in this paper, relational terms such as first and second are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations.

Claims

1. An emulsion suppository suitable for vaginal administration, said suppository being solid at room temperature and capable of in situ conversion into a cream-like formulation under vaginal temperature and moistening conditions; said suppository comprising active and pharmaceutically acceptable excipients, said excipients including structural lipids, emulsifiers, gel matrix and pH adjusters.

2. The emulsion suppository for vaginal administration according to claim 1, characterized in that, The suppository comprises, by total weight: 0.001% to 20% of active ingredients; 10%–50% of structural lipids; 2%–15% emulsifier; 0.1% to 5% gel matrix; 0.1%–3% pH adjuster; The remainder is other pharmaceutically acceptable carriers.

3. The emulsion suppository for vaginal administration according to claim 2, characterized in that, The structured lipid is selected from one or more combinations of hydrogenated coconut oil glyceride, cetearyl alcohol, glyceryl monostearate, and glyceryl distearate.

4. The emulsion suppository for vaginal administration according to claim 2, characterized in that, The emulsifier is a nonionic surfactant, preferably one or more selected from PEG-20 glyceryl stearate, polysorbate 80, sucrose fatty acid ester, and poloxamer.

5. A vaginal suppository according to claim 2, characterized in that, The gel matrix is ​​one or more of sodium carbomer, carbomer 934, hydroxypropyl methylcellulose, and sodium alginate.

6. A vaginal suppository according to claim 2, characterized in that, The pH adjuster is a buffer pair composed of organic acids and their salts, preferably a combination of lactic acid and calcium lactate. The cream formed by the conversion of the suppository in the vagina has a pH value of 3.5-5.5, preferably 4.0-5.

0.

7. A vaginal suppository according to claims 1-6, characterized in that, The active ingredient is selected from estrogen, progesterone, antibacterial drugs, antifungal drugs, or antiviral drugs; preferably, the estrogen is estradiol, estriol, estradiol valerate, or proestrene; and the progesterone is progesterone.

8. A vaginal suppository according to claim 7, characterized in that, The active ingredient and its dosage are any of the following specifications: Each suppository contains 10 mg of proestrexate, and the total weight of the suppository is 2–4 g; Each suppository contains 12.5 μg of estradiol, and the total weight of the suppository is 2–4 g; Each suppository contains 1 mg of estradiol valerate, and the total weight of the suppository is 2–4 g; Each suppository contains 400mg of progesterone, and the total weight of the suppository is 2-4g.

9. A vaginal suppository according to claims 1-6, characterized in that, The suppository completely melts into a uniform cream within 30 minutes in simulated vaginal fluid at 37°C.

10. A method for administering an emulsion suppository vaginally according to any one of claims 1-9, characterized in that, Includes the following steps: (1) The structured lipids and emulsifiers are heated and melted to form an oil phase; (2) Disperse the gel matrix and pH adjuster in purified water and stir until homogeneous to form an aqueous phase; (3) The aqueous phase is slowly added to the oil phase under stirring, the temperature is maintained and homogenization is carried out to obtain a homogeneous emulsion; (4) Add the active ingredient to the emulsion obtained in step (3) and stir until homogeneous; (5) Pour the drug-containing emulsion obtained in step (4) into the mold, cool, solidify, and demold to obtain the temperature-sensitive vaginal suppository.

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