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CN113952312A - Silodosin medicine absorbed through oral mucosa - Google Patents

Silodosin medicine absorbed through oral mucosa Download PDF

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Publication number
CN113952312A
CN113952312A CN202111291195.6A CN202111291195A CN113952312A CN 113952312 A CN113952312 A CN 113952312A CN 202111291195 A CN202111291195 A CN 202111291195A CN 113952312 A CN113952312 A CN 113952312A
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China
Prior art keywords
silodosin
medicine
oral
tabletting
oral mucosa
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CN202111291195.6A
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Chinese (zh)
Inventor
刘星
黄华
刘杰
王欣
李辽平
沈静
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CHONGQING LIYANG MEDICAL DEVELOPMENT CO LTD
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CHONGQING LIYANG MEDICAL DEVELOPMENT CO LTD
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Priority to CN202111291195.6A priority Critical patent/CN113952312A/en
Publication of CN113952312A publication Critical patent/CN113952312A/en
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
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    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
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    • A61K9/20—Pills, tablets, discs, rods
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
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    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract

The silodosin medicine absorbed through the oral mucosa takes silodosin as an effective medicine component and consists of the silodosin and acceptable auxiliary components in the oral mucosa medicine, water is not needed when the silodosin medicine is taken, the silodosin medicine is placed under the tongue or at the buccal part for dissolving, and the silodosin medicine is convenient to take, quick in effect and free of irritation to the oral cavity; the medicine is not absorbed by gastrointestinal tract basically, so that the degradation of the medicine by the gastrointestinal tract is reduced, the same or better treatment effect as an oral preparation can be achieved by lower dosage, the bioavailability is improved, the risk of adverse reaction can be reduced at the same time, and the patient has satisfactory compliance.

Description

Silodosin medicine absorbed through oral mucosa
Technical Field
The invention relates to a medicament absorbed through oral mucosa, in particular to a silodosin medicament absorbed through oral mucosa, which comprises but is not limited to sublingual tablets/particles/pills/films, buccal adhesive tablets, buccal patches and other medicinal preparations which can be completely or mainly absorbed through oral mucosa such as sublingual mucosa and/or buccal mucosa.
Background
Lower Urinary Tract Symptoms (LUTS) are common complaints among elderly men, seriously affect the quality of life of patients, and impose a heavy economic burden on individuals and society. The incidence of LUTS increases with age, and as the population of our country ages, more elderly people will suffer from LUTS. LUTS is divided into the urine storage phase, the urination phase and the symptoms after urination. Symptoms during the urine storage period include frequent micturition, urgency, incontinence and nocturia; the symptoms of the urination period comprise urination hesitancy, difficult urination, intermittent urination and the like; the symptoms after urination include incomplete urination, dribbling after urination, and the like. The cause of LUTS is mainly related to prostate diseases, and LUTS is caused by overactive bladder, urinary system infection, nocturia, etc.
Benign Prostatic Hyperplasia (BPH) is one of the most common benign diseases that cause LUTS in elderly men. Histology is characterized by hyperplasia of the interstitial and glandular components of the prostate; the anatomy is manifested as an increase in prostate volume; the clinical symptoms are mainly LUTS and urodynamic bladder outlet obstruction. Histological changes in BPH often occur after age 40 with incidence rates greater than 50% at age 60 and 83% at age 80. The urological clinic patients aged 60 years and over in China account for 47.0 percent of the diseases to be treated. Similar to histological manifestations, symptoms such as dysuria in older men increase with increasing age, with about 50% of patients histologically diagnosed with BPH having moderate to severe LUTS.
Treatment modalities for BPH/LUTS include awaiting observation, medication and surgical treatment. Awaiting observation may be taken for patients with mild or more than moderate LUTS, but whose quality of life has not been significantly affected. The drug treatment is available for patients with moderate-severe BPH/LUTS but no related complications. While moderate-severe BPH/LUTS has obviously influenced the quality of life of patients, and particularly when the drug treatment effect is poor or patients refusing to receive the drug treatment or the related complications are caused, the surgical treatment is recommended.
The alpha adrenergic receptor retarder is a first-line drug for treating BPH (BPH) which is consistently recommended by domestic and foreign guidelines, and achieves the effect of relieving dynamic obstruction of a bladder outlet by retarding adrenergic receptors distributed on smooth muscles of prostate and bladder neck and relaxing the smooth muscles.
Silodosin is a novel high-selectivity alpha 1A receptor blocker, and the affinity with an alpha 1A receptor is far higher than that of an alpha 1D receptor and an alpha 1B receptor. The results of in vitro studies showed that silodosin is 162-fold selective for prostate α 1A receptor over α 1B, which is about 17-fold that of tamsulosin (α 1A/α 1B ═ 9.55), a homoselective α 1A receptor blocker. This means that silodosin has the function of obviously relaxing the smooth muscle of the lower urinary tract, and has low incidence rate of cardiovascular adverse reactions and good cardiovascular tolerance while effectively improving the symptoms of patients with prostatic hyperplasia.
Silodosin is a white to pale yellowish white powder that melts at about 105 ℃ to 109 ℃. It is very soluble in acetic acid, very soluble in alcohol and very slightly soluble in water.
The marketed dosage forms of silodosin are only oral tablets and capsules, with a specification of 2mg, 4mg, and the systemic (blood) clearance from silodosin after administration is about 20% of the human hepatic blood flow, and the availability in the liver is estimated to be about 80%, but the bioavailability is 32.2%. The reason for this is believed to be that CYP3a4 and P-glycoprotein are involved in the metabolism of silodosin, indicating that the first pass effect in the gastrointestinal tract has a significant effect.
Disclosure of Invention
In view of the above situation, the present invention intends to provide a silodosin drug absorbed through oral mucosa, including but not limited to sublingual tablet/particle/pill/film, buccal adhesive tablet and buccal patch, etc. all or mainly absorbed through oral mucosa such as sublingual mucosa and/or buccal mucosa.
Compared with other non-oral administration routes, oral mucosa administration has the following characteristics: the blood flow of buccal mucosa and sublingual mucosa parts in oral mucosa is rich, and the blood flow speed is high; secondly, the oral mucosa has stronger tolerance to external stimulation, and when mucous membrane tissues are stimulated and damaged by some components in the preparation, the mucous membrane tissues can recover quickly after the administration is stopped; and the dosage form is easy to position, the medicine is convenient to use, and the medicine can be removed at any time. The silodosin oral mucosa drug delivery, the drug passes through sublingual mucosa and/or buccal mucosa, and is converged to the internal jugular vein through tongue vein, facial vein and the like to directly enter blood circulation, and the drug takes effect rapidly; the first-pass effect of intestines and stomach is avoided, so that the degradation of the gastrointestinal tract to the medicine is reduced, the bioavailability is improved, the same or better treatment effect can be achieved by lower administration dosage, and the adverse reaction is reduced; and the administration is convenient, and the compliance of patients is good.
In conclusion, the invention provides the silodosin medicament absorbed through the oral mucosa, which is not required to be dissolved by water when being taken, is placed under the tongue or at the buccal part for dissolving, is convenient to take, takes effect quickly and has no irritation to the oral cavity; the medicine is not absorbed by gastrointestinal tract basically, so that the degradation of the medicine by the gastrointestinal tract is reduced, the same or better treatment effect as an oral preparation can be achieved by lower dosage, the bioavailability is improved, the risk of adverse reaction can be reduced at the same time, and the patient has satisfactory compliance.
The silodosin medicine absorbed through oral mucosa is prepared with silodosin as effective component and auxiliary components acceptable in oral mucosa medicine. Wherein, the acceptable auxiliary components in the oral mucosa medicament can select various auxiliary components which are usually required and/or used in the oral mucosa medicament preparation at present, and comprise:
diluent agent: such as microcrystalline cellulose, lactose, the lactose complex Ludipress (consisting of lactose, Kollidon 30 and Kollidon CL), Ludipress LCE (consisting of lactose and Kollidon 30), Ludipash (consisting of 90% Mannitol, 5%
Figure BSA0000256681830000031
CL-SF and 5%
Figure BSA0000256681830000032
SR 30D), Cellactose 80, Tablettose 80, MicroceLac 100, StarLac, Prosolv HD 90, starch, pregelatinized starch, powdered sugar, glucose, calcium sulfate, dextrin, mannitol, erythritol, maltose, maltitol, maltodextrin, sorbitol and xylitol.
Adhesive: such as common polyvidone components (such as Kollidon VA 64, Kollidon VA 64Fine, Plasdone S-630), starch slurry, hydroxypropyl methylcellulose, carrageenan, carbomer, guar gum, gelatin, acacia, xanthan gum, alginic acid or one or more of sodium alginate, potassium alginate, calcium alginate and other salts thereof, propylene glycol alginate and other various components, and sodium starch phosphate, chitosan, dextrin and syrup.
Wetting agent: such as one or more of common water, ethanol, absolute ethanol and ethanol solutions with different concentrations.
Disintegrating agent: such as one or more of crospovidone, sodium carboxymethyl starch, sodium croscarmellose, low substituted hydroxypropyl cellulose, microcrystalline cellulose-aerosil, pregelatinized starch, dry starch, sodium alginate, alginic acid, hydroxypropyl starch, and calcium carboxymethyl cellulose, and the dosage of the composition is generally 0.1-50% of the total weight of the tablet.
Taste masking (flavoring) agent: such as one or more of commonly used sweeteners and/or flavoring ingredients such as glycyrrhizin, aspartame, crystalline maltose, Treated Agar (TAG), stevioside, sucralose, xanthan gum, saccharin, vitamin C, fructose, dextran, sodium cyclamate, thaumatin, saccharin, menthol, etc.
Lubricant: such as one or more of magnesium stearate, stearic acid, sodium stearyl fumarate, sodium lauryl sulfate, polyethylene glycol 4000 (or polyethylene glycol 6000), silica gel micropowder, and pulvis Talci.
Absorption accelerator: a polysorbate; ethers of polyoxyethylene with alkyl groups; esters of polyoxyethylene with fatty acids; a fatty acid; a fatty alcohol; cholic acid and salts thereof with pharmaceutically acceptable cations; esters of C1-C6 fatty alcohols with fatty acids; esters of polyols and fatty acids, said polyols containing 2-6 hydroxyl functional groups; a polyglycolysed glyceride; one or more of sodium dodecyl sulfate and the like.
Light screening agent: one or more of the allowable opacifier components such as titanium dioxide, ferric oxide, ferroferric oxide, zinc oxide and the like.
Dripping pill matrix: polyethylene glycol 6000, polyethylene glycol 4000, polyethylene glycol 300, sodium stearate, and/or glycerogelatin.
Film-forming materials: polyvinyl alcohol, ethylene-vinyl acetate copolymer, hydroxypropyl methyl cellulose, povidone, and hydroxypropyl cellulose; film-forming plasticizer: glycerin, sorbitol; surfactant (b): polysorbate 80, sodium lauryl sulfate; filling agent: calcium carbonate, silica, starch; colorant: pigment, titanium dioxide and one or more of stripper liquid paraffin.
The silodosin in the medicine absorbed through the oral mucosa is contained under the tongue of the oral cavity, in the buccal cavity or in other parts of the oral cavity, is absorbed and acted by the mucosa tissues in the oral cavity such as the sublingual mucosa and the buccal mucosa, and the like completely or basically, and the specific preparation forms of the silodosin can comprise sublingual tablets/particles/pills/films, buccal tablets/particles/pills/films, oral adhesive tablets, oral patches and the like which are used at present.
In the above-mentioned medicine of the present invention, the content of said effective medicine component silodosin in the medicine preparation can be generally 0.1% -100% of total weight of medicine, and the dosage of the above-mentioned auxiliary components can be respectively used according to the conventional mode of every existent correspondent preparation.
The preparation of the medicine absorbed by oral mucosa can be prepared by adopting the conventional mode of the prior similar medicine preparation. Taking tablets as an example, a typical preparation method can be as follows:
a. and (3) dry granulation and tabletting mode: mixing the active pharmaceutical ingredient silodosin and the selected auxiliary ingredients uniformly, directly pressing into blocks, crushing into granules, and tabletting to obtain the finished product.
b. And (3) wet granulation and tabletting mode: mixing the effective medicinal component silodosin and the added auxiliary components uniformly, adding an adhesive and/or a wetting agent for granulation, drying, adding (or not adding) additional auxiliary materials (a lubricant and/or a disintegrating agent), mixing uniformly, and tabletting to obtain the finished product.
c. Powder direct compression mode: mixing the active pharmaceutical ingredient silodosin and the selected auxiliary ingredients uniformly, and directly tabletting to obtain the finished product.
d. And (3) granulating and tabletting by a semi-dry method: mixing the selected auxiliary components, adding binder and/or wetting agent, granulating, drying, adding effective medicinal components (optionally adding adjuvant such as lubricant and/or disintegrant), mixing, and tabletting.
e. A freeze drying tabletting mode: mixing the effective medicinal component silodosin, excipient and other auxiliary materials with a solvent to prepare a liquid medicine, filling the prepared liquid medicine into a bubble cap, and freeze-drying in a freeze dryer to obtain a finished product.
In a typical preparation method of the tablet, the active pharmaceutical ingredient silodosin can be pretreated independently or together with all or part of the auxiliary ingredients or not, and can be mixed with selected auxiliary ingredients in the forms of crystals, powder, micropowder, solid dispersion and/or inclusion compound, and the like, granulated, dried, granulated and tableted; or mixing with selected auxiliary components (prepared into blank granule in advance) and tabletting; or mixing with selected adjuvant, and tabletting.
The silodosin medicine in the form can achieve the same or better treatment effect as an oral preparation by lower dosage, and improve the bioavailability; the onset speed is faster than that of oral tablets; the medicine is taken without water, and is more convenient. Can satisfactorily solve the defects of large gastrointestinal tract first pass effect and low bioavailability of oral tablets, improve the curative effect, reduce adverse reactions, have more ideal patient compliance, ensure that BPH patients can be treated safely and effectively more quickly, and relieve the pain of the patients quickly.
The above-mentioned contents of the present invention will be further described in detail by the following specific embodiments of examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. Various substitutions and alterations according to the general knowledge and conventional practice in the art are intended to be included within the scope of the present invention without departing from the technical spirit of the present invention as described above.
Detailed Description
Example 1 (buccal tablet, 0.1-8 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000051
the preparation method comprises the following steps: micronization pretreatment of silodosin to D90Mixing the raw materials with auxiliary components such as starch, pregelatinized starch and the like uniformly, adding 5% povidone aqueous solution for granulation, drying by a fluidized bed, granulating, adding magnesium stearate, mixing uniformly, tabletting and packaging to obtain the finished product. The solubility meets the relevant requirements. It is administered orally and buccally.
Example 2 (buccal tablet, 2.5 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000061
the preparation method comprises the following steps: micronization pretreatment of silodosin to D90Mixing with lactose, pregelatinized starch, erythritol and other auxiliary components, tabletting and packing. The solubility meets the relevant requirements. It is administered orally and buccally.
Example 3 (buccal tablet, 3.5 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000062
the preparation method comprises the following steps: micronization pretreatment of silodosin to D90Mixing with Ludipress LCE, microcrystalline cellulose and other auxiliary components uniformly, adding sodium stearyl fumarate, mixing uniformly, directly tabletting and packaging to obtain the tablet. Solubility symbolAnd (5) meeting the relevant requirements. It is administered orally and buccally.
Example 4 (Sublingual tablet, 1.2 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000063
Figure BSA0000256681830000071
the preparation method comprises the following steps: micronization pretreatment of silodosin to D90Mixing with corn starch and other supplementary material, tabletting and packing. The disintegration time meets the relevant requirements. When administered, it is placed under tongue and dissolved.
Example 5 (oral Patch or oral adhesive tablet, 4 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000072
the preparation method comprises the following steps: micronization pretreatment of silodosin to D90Mixing with auxiliary components such as maltose, sorbitol, carbomer and hydroxypropyl methylcellulose uniformly, tabletting to obtain the oral cavity adhesive tablet, or preparing according to the tablet process, and packaging. The release degree meets the requirements. When taken, the medicine is stuck or adhered to the cheek or other parts of the oral cavity to be gradually dissolved.
Example 6 (Sublingual tablet, 2 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000073
the preparation method comprises the following steps: micronization pretreatment of silodosin to D90Mixing with 10-20 μm of mannitol and starch, placing in fluidized bed, and granulating with purified waterDrying, grading, adding silica gel micropowder, tabletting, and packaging. The disintegration time meets the relevant requirements. When administered, it is placed under tongue and dissolved.
Example 7 (Sublingual tablet, 3.2 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000081
the preparation method comprises the following steps: micronization pretreatment of silodosin to D90Sieving the powder with auxiliary components of maltodextrin, microcrystalline cellulose, sodium carboxymethyl starch and the like through a 100-mesh sieve, uniformly mixing, adding a proper amount of 8% starch slurry, granulating, drying, finishing granules, adding additional sodium carboxymethyl starch and sodium stearyl fumarate, tabletting and packaging. The disintegration time meets the relevant requirements. When administered, it is placed under tongue and dissolved.
Example 8 (Sublingual tablet, 2.6 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000082
the preparation method comprises the following steps: sieving silodosin, xylitol, pregelatinized starch and other auxiliary components with 100 mesh sieve, mixing, granulating with a dry granulating machine, grading, adding stearic acid and crospovidone, mixing, tabletting, and packaging. The disintegration time meets the relevant requirements. When administered, it is placed under tongue and dissolved.
Example 9 (Sublingual tablet, 1.6 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000091
the preparation method comprises the following steps: sieving auxiliary components such as mannitol and corn starch with 100 mesh sieve, adding silodosin, mixing, tabletting, and packaging. The disintegration time meets the relevant requirements. When administered, it is placed under tongue and dissolved.
Example 10 (Sublingual tablet, 0.8 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000092
the preparation method comprises the following steps: mixing silodosin with polyvidone K30Preparing silodosin-povidone K by solvent method (such as ethanol as solvent)30And (3) drying the solid dispersion, detecting the content of silodosin in the solid dispersion, crushing and sieving the solid dispersion, sieving the crushed solid dispersion with auxiliary components such as lactose, microcrystalline cellulose, glucan and the like through a 100-mesh sieve, uniformly mixing, tabletting and packaging to obtain the xyloglucan. The disintegration time meets the relevant requirements. When administered, it is placed under tongue and dissolved.
Example 11 (Sublingual tablet, 0.5 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000093
Figure BSA0000256681830000101
the preparation method comprises the following steps: preparing the silodosin and hydroxypropyl beta-cyclodextrin into an inclusion compound by a spray drying method, detecting the content of the silodosin in the inclusion compound, crushing and sieving the silodosin-hydroxypropyl beta-cyclodextrin inclusion compound, sieving auxiliary components such as microcrystalline cellulose, stevioside and the like by a 100-mesh sieve, uniformly mixing, tabletting and packaging. The disintegration time meets the relevant requirements. When administered, it is placed under tongue and dissolved.
Example 12 (Sublingual tablet, 3.2 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000102
the preparation method comprises the following steps: sieving silodosin, starch, erythritol and other auxiliary components with 100 mesh sieve, adding into an extrusion spheronizer, extruding with purified water, spheronizing, granulating, adding stearic acid, mixing, tabletting, and packaging. The disintegration time meets the relevant requirements. When administered, it is placed under tongue and dissolved.
Example 13 (Sublingual tablet, 2.5 mg/tablet)
Consists of the following components:
Figure BSA0000256681830000103
the preparation method comprises the following steps: weighing silodosin, mannitol and the like according to the prescription amount, dissolving in water, then placing in a freeze dryer for low-temperature quick freezing and forming, sublimating the frozen medicine under the conditions of high vacuum and low temperature, removing water, properly drying to remove residual water, tabletting and packaging. The disintegration time meets the relevant requirements. When administered, it is placed under tongue and dissolved.
Example 14 (drop pill, 1 mg/pill)
Consists of the following components:
Figure BSA0000256681830000111
the preparation method comprises the following steps: according to the dropping method, the silodosin is added into the molten polyethylene glycol 4000, the mixture is continuously stirred to be completely molten, the mixture is filtered while the mixture is hot, the mixture is placed into a liquid storage bottle for heat preservation, the mixture is dropped into liquid paraffin condensate by a dropper to be condensed into pills, and the pills are packaged. The dissolution time limit meets the requirement. When administered, the composition is placed under tongue or buccal region for buccal administration.
Example 15 (pellet, 1 mg/pellet)
Consists of the following components:
Figure BSA0000256681830000112
the preparation method comprises the following steps: adding the blank pill core (sugar pill) into fluidized bed, spraying aqueous solution of silodosin at the bottom, making into pellet, and packaging. The dissolution time limit meets the requirement. When administered, the composition is placed under tongue or buccal region for buccal administration.
Example 16 (Sublingual buccal granule, 3mg)
Consists of the following components:
Figure BSA0000256681830000113
the preparation method comprises the following steps: sieving silodosin and adjuvants such as lactose and mannitol with 80 mesh sieve, mixing, adding 10% starch slurry, granulating, drying, grading, and packaging. The disintegration time meets the relevant requirements. When administered, it is placed under tongue and dissolved.
Example 17 (film agent, 0.3%)
Consists of the following components:
Figure BSA0000256681830000121
the preparation method comprises the following steps: weighing silodosin, adding the silodosin into purified water, uniformly stirring and dispersing, weighing titanium dioxide and glycerol, adding the titanium dioxide and the glycerol into the purified water, uniformly stirring and dispersing, adding polyvinyl alcohol into the uniformly dispersed solution, fully stirring and dissolving to form glue solution, and carrying out vacuum pumping, centrifugal defoaming on the glue solution. And (4) injecting the glue solution into a coating machine, and coating. Cutting according to specification, and packaging. The disintegration and dissolution time meets the requirements. When administered, the composition is placed under tongue or buccal region for buccal administration.
Although the spirit of the present invention has been described in the above embodiments, it is only for illustrative purposes and not for limiting the present invention, and variations of the embodiments will become apparent to those skilled in the art after reading the technical lines of the present invention or the embodiments. Thus, modifications and variations may be made to the embodiments of the invention without departing from the scope and spirit of the invention, which is to be accorded an equivalent to the present invention.

Claims (6)

1. The medicine absorbed through oral mucosa contains silodosin as effective component and auxiliary component acceptable in oral mucosa medicine, and features that silodosin in 0.1-8.0 mg/unit dosage.
2. The drug substance of silodosin absorbed through oral mucosa according to claim 1, wherein the dosage form is tablet, granule, pill, film, buccal adhesive tablet, buccal patch, etc.
3. The drug substance of silodosin absorbed through oral mucosa according to claims 1 and 2, wherein the granules are prepared by dry granulation and wet granulation processes, and the tablets are prepared by dry granulation tabletting, wet granulation tabletting, semi-dry granulation tabletting, direct powder tabletting and freeze-drying tabletting processes.
4. The orodoracin pharmaceutical composition for oral transmucosal absorption according to claims 1 and 2, characterized in that it is prepared by a pill preparation method.
5. The oral transmucosal celecoxib drug according to claims 1 and 2, wherein the film preparation is carried out by a film preparation method.
6. The orodocin drug for oral transmucosal absorption according to claims 3, 4, and 5, wherein the active pharmaceutical ingredient silodocin is pretreated alone or together with all or part of the auxiliary ingredients or without pretreatment, and can be prepared in the form of crystals, powders, fine powders, solid dispersions, and/or inclusion compounds, together with the selected auxiliary ingredients, in the form of tablets, granules, pills, films, oroadhesive tablets, and buccal patches.
CN202111291195.6A 2021-10-24 2021-10-24 Silodosin medicine absorbed through oral mucosa Pending CN113952312A (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004175796A (en) * 2002-11-13 2004-06-24 Asahi Kasei Pharma Kk Intraoral disintegrating preparation for treating dysuria
CN1747722A (en) * 2003-02-04 2006-03-15 赛福伦公司 Sugar-free oral transmucosal solid dosage forms and uses thereof
CN102716097A (en) * 2012-05-29 2012-10-10 浙江华海药业股份有限公司 Method for controlling medicament release rate of orally disintegrating tablet
US20140142076A1 (en) * 2012-11-14 2014-05-22 Abon Pharmaceuticals, Llc Oral transmucosal drug delivery system
CN103933001A (en) * 2014-05-09 2014-07-23 浙江华海药业股份有限公司 Stable silodosin oral solid pharmaceutical composition and preparation method thereof
CN108136032A (en) * 2015-10-05 2018-06-08 大同化成工业株式会社 Include the Composite granules and its manufacturing method of sugared or sugar alcohol, swellable adhesive, disintegrant and high-absorbable excipient

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004175796A (en) * 2002-11-13 2004-06-24 Asahi Kasei Pharma Kk Intraoral disintegrating preparation for treating dysuria
CN1747722A (en) * 2003-02-04 2006-03-15 赛福伦公司 Sugar-free oral transmucosal solid dosage forms and uses thereof
CN102716097A (en) * 2012-05-29 2012-10-10 浙江华海药业股份有限公司 Method for controlling medicament release rate of orally disintegrating tablet
US20140142076A1 (en) * 2012-11-14 2014-05-22 Abon Pharmaceuticals, Llc Oral transmucosal drug delivery system
CN103933001A (en) * 2014-05-09 2014-07-23 浙江华海药业股份有限公司 Stable silodosin oral solid pharmaceutical composition and preparation method thereof
CN108136032A (en) * 2015-10-05 2018-06-08 大同化成工业株式会社 Include the Composite granules and its manufacturing method of sugared or sugar alcohol, swellable adhesive, disintegrant and high-absorbable excipient

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Application publication date: 20220121