CN110833530A - Dapoxetine hydrochloride orally disintegrating tablet and preparation method and application thereof - Google Patents
Dapoxetine hydrochloride orally disintegrating tablet and preparation method and application thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
Abstract
The invention discloses a dapoxetine hydrochloride orally disintegrating tablet and a preparation method thereof. The orally disintegrating tablet comprises dapoxetine hydrochloride, a filling agent, a disintegrating agent, a dry adhesive, a penetration-promoting flavoring agent and a lubricating agent, and the preparation method adopts a direct tabletting method. The invention has the characteristics of simple preparation process, low cost, convenient taking and quick response to male premature ejaculation indication. The dapoxetine hydrochloride orally disintegrating tablet disclosed by the invention is combined with 0.1% -2% of a penetration-promoting corrigent, so that the taste of the tablet is improved, the stability of the tablet is improved, the absorption of the tablet is further increased, the maximum plasma concentration (Cmax) is reached within 0.5-1 hour after the tablet is orally taken, the onset time is remarkably accelerated, and the bioavailability is remarkably improved.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a dapoxetine hydrochloride orally disintegrating tablet, and a preparation method and application thereof.
Background
The dapoxetine hydrochloride is white to off-white crystalline powder and is easy to oxidize. The chemical name is (S) - (+) -N, N-dimethyl-3- (1-naphthoxy) amphetamine hydrochloride, and the structural formula is as follows:
dapoxetine researched and developed by the earliest American Gift pharmaceutical company (Eli Lilly) is used for treating depression and is subjected to phase I clinical test, the depression effect of dapoxetine is not ideal, and then the product is transferred to a PP day pharmaceutical group and is used for treating premature ejaculation patients after being discovered by a PP day Genu Pro research of a subsidiary company of the product, and phase II clinical test is carried out; finally, the product is completely transferred to the part of Alerzang flag of Qiangsheng company, is used for treating premature ejaculation patients, and is tried out in 60 medical centers in the United states when in phase III clinical test. In 2008, the Yansen company disclosed the clinical trial data of stage III of premature ejaculation patients treated with dapoxetine in the 100 th national urinary society scientific conference (AUA-2005), and the results of the drug interaction and pharmacodynamic test of the drug were disclosed in the conference. The experimental data show that the dapoxetine has the advantages of short half-life period, small adverse reaction to patients and excellent treatment effect when being used as the medicament for treating the disease of premature ejaculation.
Dapoxetine hydrochloride (Tianapoxetine Hy Tianrochlori Tian e) is a rapid and efficient selective 5-hydroxytryptamine reuptake inhibitor (SSRI), and the action mechanism of the dapoxetine Hy Tianrochlori Tianchlori hydrochloride for treating premature ejaculation is possibly related to the action mechanism of the dapoxetine Hy rochloride inhibitor for inhibiting the reuptake of neurons on 5-hydroxytryptamine so as to influence the potential difference of neurotransmitters acting on receptors before and after synapses of cells.
At present, dapoxetine hydrochloride tablets (Bi Li Jing) are marketed at home and abroad®Or Priligy®) Is a common tablet, needs to be taken with warm water about 1 to 3 hours before sexual life, has poor patient compliance, slow drug absorption and slow onset of action, achieves maximum plasma concentration (Cmax) after about 1 to 2 hours after oral administration, and has an absolute bioavailability of only 42% (ranging from 15 to 76%). The dapoxetine hydrochloride indication is used for treating male premature ejaculation, so that the medicament is required to be rapidly released to achieve the purpose of quick response.
In the prior art, patent CN201610492468.6 discloses a preparation method of a dapoxetine sustained-release preparation, which achieves the aims of small toxic and side effects and high safety of the sustained-release preparation, but the indication of the dapoxetine determines the characteristic that the preparation needs to take effect quickly, and the sustained-release preparation has no practical value. Patent CN201510827956.3 discloses a preparation process of preparing dapoxetine hydrochloride into a solid dispersion, and then directly tabletting with auxiliary materials, wherein the tablet prepared by the process is fast in dissolution and can be rapidly released, but organic solvents are used in the process, and the problems of organic solvent residue and the like need to be concerned in the later period, and the process is complex and has low practical operability.
The direct powder compression is to directly compress the powder of the medicine and proper auxiliary materials into tablets without granulation after sieving and mixing the powder and the proper auxiliary materials respectively. The most significant advantage of the direct powder compression technique over conventional wet granulation is its economy and the tablets produced using the direct powder compression technique have good disintegration properties and excellent dispersion uniformity.
Disclosure of Invention
In order to solve the technical problems, the invention provides a dapoxetine hydrochloride orally disintegrating tablet which comprises the following specific components in percentage by weight:
20-40% of dapoxetine hydrochloride
30 to 60 percent of filling agent
5 to 15 percent of disintegrating agent
3 to 10 percent of dry adhesive
Penetration-promoting correctant 0.1-2%
0.5 to 4 percent of lubricant
The orally disintegrating tablet (orally disintegrating tablet) can be quickly dissolved in saliva or can be quickly disintegrated in the oral cavity, a patient does not need water or chew, the medicine is placed in the oral cavity, is quickly dissolved or disintegrated along with the saliva and takes effect after entering a digestive system along with the autonomous and involuntary swallowing actions of the user, and the orally disintegrating tablet has the advantages of convenience in use, quickness in absorption, high bioavailability and the like.
The penetration-promoting corrigent is an auxiliary material with dual functions of penetration promotion and taste correction, the penetration promotion function is realized in a certain concentration range, the penetration promotion function is not realized when the concentration is too low, and the drug absorption is inhibited when the concentration is too high. The penetration-promoting correctant, namely the menthol, also has a certain antioxidation effect, has a protection function on substances easy to oxidize, and improves the stability. The dapoxetine hydrochloride has bitter taste and is easy to oxidize, and the oral disintegrating tablet with improved taste and stability and improved bioavailability is prepared by combining the raw material medicines with poorer taste with the permeation-promoting corrigent menthol with certain concentration.
Further, the filler is one or more of lactose, microcrystalline cellulose, sorbitol, mannitol, and xylitol, preferably mannitol. Wherein, the mannitol adopts direct-compression mannitol, the direct-compression mannitol has good fluidity and compressibility, and the feasibility of a direct-compression process is ensured.
Further, the disintegrating agent is one or more of croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, calcium carboxymethyl cellulose and sodium carboxymethyl cellulose. The disintegrant is preferably crospovidone or croscarmellose sodium or mixture thereof, so that the preparation has rapid disintegrating effect and improved bioavailability.
Further, the dry adhesive is methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvidone, and ethyl cellulose. The dry adhesive is preferably hydroxypropyl cellulose which is easy to be pressed and formed, has strong applicability, not only improves the hardness and the appearance brightness of the tablet, but also ensures that the tablet is quickly disintegrated, is beneficial to the implementation of a simple direct pressing process and further improves the bioavailability.
Further, the penetration-promoting correctant is menthol and nerolidol. Menthol is preferred to improve the permeability of the formulation. The source of the menthol is wide, the application is convenient and fast, and the menthol meets the requirements of the public on taste.
Further, the lubricant is one or more of magnesium stearate, sodium stearyl fumarate, superfine silica gel powder and talcum powder.
Further, the weight of the dapoxetine hydrochloride orally disintegrating tablet is 100 mg-200 mg, and the hardness is 20N-60N.
The dapoxetine hydrochloride orally disintegrating tablet of the invention has far faster effect than that of the products for treating premature ejaculation sold in the market at present, and can be widely used for preparing the medicines for treating premature ejaculation.
A preparation method of dapoxetine hydrochloride orally disintegrating tablets comprises the following steps:
(1) respectively sieving the raw materials and the auxiliary materials with a 80-mesh sieve for later use;
(2) uniformly mixing the bulk drugs, the filler, the disintegrant and the dry adhesive according to the prescription amount to obtain premixed powder;
(3) adding the penetration-promoting flavoring agent and the lubricant in the prescribed amount into the premixed powder obtained in the step (2), and uniformly mixing to obtain total mixed powder;
(4) and tabletting the total mixed powder by adopting a direct pressing process.
Compared with the prior art, the invention adopts a direct compression process, has the characteristics of simple preparation process, improved taste, low cost, convenient taking and quick response to male premature ejaculation indications, and achieves the maximum plasma concentration (Cmax) within 0.5 to 1 hour after oral administration, thereby obviously accelerating the response time and obviously improving the bioavailability. The invention does not need to add additives such as chain extender, stabilizer and the like in the synthetic process, so that the copolyester product is pure.
Drawings
FIG. 1 is a graph showing the mean time course of the drugs in examples 5 and 6 of the present invention and comparative example 6. Detailed Description
The invention is further described below with reference to the following examples, but without limiting the invention thereto.
Example 1
Dapoxetine hydrochloride tablet (1000 tablets in batch)
| Dapoxetine hydrochloride | 34g |
| Mannitol | 45g |
| Cross-linked polyvidone | 8g |
| Croscarmellose sodium | 3g |
| Hydroxypropyl cellulose | 8g |
| Menthol crystal | 1g |
| Magnesium stearate | 1g |
The preparation method comprises the following steps:
(1) screening the dapoxetine hydrochloride and the auxiliary materials through a 80-mesh screen for later use;
(2) mixing the dapoxetine hydrochloride, mannitol, crospovidone, croscarmellose sodium and hydroxypropyl cellulose for 20min to obtain uniformly mixed premixed powder;
(3) adding menthol and magnesium stearate according to the prescription amount, and mixing for 2min to obtain total mixed powder;
(4) and tabletting the total mixed powder by adopting a direct compression process, and controlling the weight of the tablet to be 100mg and the hardness to be 40N.
Example 2
Dapoxetine hydrochloride tablet (1000 tablets in batch)
| Dapoxetine hydrochloride | 20g |
| Mannitol | 60g |
| Cross-linked polyvidone | 2.5g |
| Croscarmellose sodium | 10g |
| Hydroxypropyl cellulose | 5g |
| Menthol crystal | 1g |
| Magnesium stearate | 4g |
The preparation method comprises the following steps:
(1) screening the dapoxetine hydrochloride and the auxiliary materials through a 80-mesh screen for later use;
(2) mixing dapoxetine hydrochloride, mannitol, crospovidone, croscarmellose sodium and hydroxypropyl cellulose for 20min to obtain uniformly mixed premixed powder;
(3) adding menthol and magnesium stearate according to the prescription amount, and mixing for 2min to obtain total mixed powder;
(4) and tabletting the total mixed powder by adopting a direct compression process, and controlling the weight of the tablet to be 100mg and the hardness to be 20N.
Example 3
Dapoxetine hydrochloride tablet (1000 tablets in batch)
| Dapoxetine hydrochloride | 60g |
| Mannitol | 45g |
| Croscarmellose sodium | 22.5g |
| Hydroxypropyl cellulose | 15g |
| Menthol crystal | 2.25g |
| Magnesium stearate | 2.25g |
| Silica gel micropowder | 3g |
The preparation method comprises the following steps:
(1) screening the dapoxetine hydrochloride and the auxiliary materials through a 80-mesh screen for later use;
(2) mixing dapoxetine hydrochloride, mannitol, croscarmellose sodium and hydroxypropyl cellulose for 20min to obtain uniformly mixed premixed powder;
(3) adding the menthol, the magnesium stearate and the superfine silica powder according to the prescription amount, and mixing for 2min to obtain total mixed powder;
(4) and tabletting the total mixed powder by adopting a direct compression process, and controlling the weight of the tablet to be 150mg and the hardness to be 60N.
Example 4
Dapoxetine hydrochloride tablet (1000 tablets in batch)
| Dapoxetine hydrochloride | 68g |
| Mannitol | 110g |
| Cross-linked polyvidone | 13g |
| Hydroxypropyl cellulose | 6g |
| Menthol crystal | 2g |
| Stearic acid sodium fumarate | 0.5g |
| Silica gel micropowder | 0.5g |
The preparation method comprises the following steps:
(1) screening the dapoxetine hydrochloride and the auxiliary materials through a 80-mesh screen for later use;
(2) mixing dapoxetine hydrochloride, mannitol, polyvinylpolypyrrolidone and hydroxypropyl cellulose for 20min to obtain uniformly mixed premixed powder;
(3) adding the formula amount of menthol, sodium stearyl fumarate and micropowder silica gel, and mixing for 2min to obtain total mixed powder;
(4) and tabletting the total mixed powder by adopting a direct compression process, and controlling the weight of the tablet to be 200mg and the hardness to be 40N.
Example 5
Dapoxetine hydrochloride tablet (1000 tablets in batch)
| Dapoxetine hydrochloride | 34g |
| Mannitol | 46.9g |
| Cross-linked polyvidone | 8g |
| Hydroxypropyl cellulose | 8g |
| Menthol crystal | 0.1g |
| Stearin rich inMaleic acid sodium salt | 3g |
The preparation method comprises the following steps:
(1) screening the dapoxetine hydrochloride and the auxiliary materials through a 80-mesh screen for later use;
(2) mixing dapoxetine hydrochloride, mannitol, polyvinylpolypyrrolidone and hydroxypropyl cellulose for 20min to obtain uniformly mixed premixed powder;
(3) adding the menthol and the sodium stearyl fumarate according to the prescription amount, and mixing for 2min to obtain total mixed powder;
(4) and tabletting the total mixed powder by adopting a direct compression process, and controlling the weight of the tablet to be 100mg and the hardness to be 40N.
Example 6
Dapoxetine hydrochloride tablet (1000 tablets in batch)
| Dapoxetine hydrochloride | 34g |
| Mannitol | 45g |
| Cross-linked polyvidone | 8g |
| Hydroxypropyl cellulose | 8g |
| Menthol crystal | 2g |
| Stearic acid sodium fumarate | 3g |
The preparation method comprises the following steps:
(1) screening the dapoxetine hydrochloride and the auxiliary materials through a 80-mesh screen for later use;
(2) mixing dapoxetine hydrochloride, mannitol, polyvinylpolypyrrolidone and hydroxypropyl cellulose for 20min to obtain uniformly mixed premixed powder;
(3) adding the menthol and the sodium stearyl fumarate according to the prescription amount, and mixing for 2min to obtain total mixed powder;
(4) and tabletting the total mixed powder by adopting a direct compression process, and controlling the weight of the tablet to be 100mg and the hardness to be 40N.
Comparative example 6
Dapoxetine hydrochloride tablet (1000 tablets in batch)
| Dapoxetine hydrochloride | 34g |
| Mannitol | 47g |
| Cross-linked polyvidone | 8g |
| Hydroxypropyl cellulose | 8g |
| Stearic acid sodium fumarate | 3g |
The preparation method comprises the following steps:
compared with the prescription composition of example 6, the formula composition is not added with menthol, and the preparation process is consistent with that of example 6.
The results of the taste examination of examples 1 to 6 and comparative example 6 were as follows:
table 1: taste investigation result of dapoxetine hydrochloride orally disintegrating tablet
As can be seen from Table 1, the samples of examples 1-6 and comparative example 6 all disintegrated rapidly, the samples of examples 1-6 had good mouthfeel and satisfied the mouthfeel requirements of patients on orally disintegrating tablets, while the sample of comparative example 6, which was not added with menthol, had poor mouthfeel, failed to satisfy the mouthfeel requirements of patients on orally disintegrating tablets, and had poor compliance. The penetration-promoting corrective can cover the bitter and astringent feeling of the medicine and better improve the taste. Therefore, the menthol is added in the formula of the invention to solve the problem of the bitter and astringent feeling of dapoxetine hydrochloride.
Examples 1-6, comparative example 6 and commercially available dapoxetine hydrochloride tablets (briq. RTM®Or Priligy®) Comparing dissolution rates, and selecting 0.1mol/L hydrochloric acid according to dissolution rate determination method (0931 method of the four general rules of the pharmacopoeia 2015 edition)Medium, volume 500ml, rotation speed 50rpm, n = 12. The results are as follows:
table 2: comparison of the cumulative dissolution rate (n = 12) of dapoxetine hydrochloride orally disintegrating tablets with a commercially available control formulation
| Time of day | Example 1 Cumulative solution Degree of departure (%) | Example 2 Cumulative dissolution Degree (%) | Example 3 Cumulative dissolution Degree (%) | Example 4 Cumulative dissolution Degree (%) | Example 5 Cumulative solution Degree of departure (%) | Example 6 Cumulative solution Degree of departure (%) | Comparative example Example 6 cumulative solution Degree of departure (%) | Commercial control formulation Cumulative dissolution (%) |
| 5min | 94.15 | 92.88 | 92.79 | 91.21 | 91.35 | 93.17 | 90.18 | 20.15 |
| 10min | 97.12 | 96.58 | 93.05 | 95.78 | 93.70 | 96.62 | 91.16 | 53.55 |
| 15min | 99.73 | 98.79 | 100.01 | 98.75 | 95.43 | 98.86 | 93.15 | 75.27 |
| 30min | 100.03 | 99.92 | 100.38 | 99.75 | 97.88 | 99.25 | 98.88 | 89.12 |
As can be seen from Table 2, the samples of examples 1 to 6 and comparative example 6 are very fast and complete in dissolution, and are significantly faster than the dissolution of the commercially available reference substance, and the samples of examples 1 to 6 and comparative example 6 are completely dissolved before entering the gastrointestinal tract, so that the gastrointestinal tract absorption is facilitated, the rapid onset of action is realized, and the bioavailability is improved.
Examples 1-6, comparative example 6 were blister-packaged with commercially available dapoxetine hydrochloride tablets (briq. RTM®Or Priligy®) The mixture is placed under an accelerated condition (the temperature is 40 ℃ plus or minus 2 ℃, and the relative humidity is 75 percent plus or minus 5 percent) for six months, and the stability is compared as follows:
table 3: comparison of stability of dapoxetine hydrochloride orally disintegrating tablet and commercial control preparation in six-month accelerated test
As can be seen from Table 3, after the samples of examples 1-6 were left under accelerated conditions for six months, the content, the related substances and the dissolution rate of the samples were not different from 0 day, the samples were stable, and compared with the commercial control preparation, the content, the related substances and the dissolution rate of the samples were not significantly different, and the dissolution rate was significantly increased compared with the commercial control preparation. After the sample in comparative example 6 is placed under an accelerated condition for 6 months, compared with 0 day, the content of the sample is reduced, related substances are obviously increased, the sample is unstable, compared with the sample in example 6, the content of the sample is reduced, the related substances are increased, and the dissolution is not significantly different; compared with the commercial control preparation, the content of the sample is reduced, the related substances are increased, and the dissolution is obviously increased compared with the commercial control preparation. The menthol added in the prescription of the invention has obvious stabilizing effect on the sample.
Pharmacokinetic experiments were performed on example 5, example 6 and comparative example 6 to compare bioavailability. The specific test method is as follows:
healthy male beagle dogs were selected at 18 weight (10. + -. 1.0) kg. No drug was used 14 days before the experiment, compared to 20 days 1: 00 fasting was started, with the test at 7: 00 taking the preparation with specified dosage on empty stomach, and taking food 4h after taking the preparation.
The dosing regimen was designed using a three-formulation three-cycle crossover trial. The 18 beagles were randomly numbered and randomly divided into 6 groups of 3 beagles each, namely, A, B, C, D, E and Z. The drugs of example 5, example 6 and comparative example 6 were taken at random. The random grouping and dosing regimen are shown in table 4 below. The 3 preparations were all administered orally. The experiments were separated by 7 days per week. 3.0ml of blood is taken from forelimb veins and placed in an anticoagulation tube for drug concentration analysis at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0 and 8.0h before (0 h) and after administration. The mean time curve of the mean drugs of example 5, example 6 and comparative example 6 is shown in fig. 1, and is classified according to the administration, for example, the mean value of the blood concentration of 18 dogs taking the drug of example 5 at different time points.
Table 4: triple crossover test beagle dosing regimens
And (3) test results: as can be seen from FIG. 1, the plasma concentration of beagle dogs in example 5 (menthol to 0.1%) and example 6 (menthol to 2%) of the present invention peaked within 1 hour after administration, while the plasma concentration of comparative example 6 (without menthol) peaked within 2 hours after administration. The orally disintegrating tablet added with the penetration-promoting corrigent is easy to absorb and has the characteristic of quick response; by calculation, when the bioavailability of comparative example 6 (without adding menthol) is 100%, the bioavailability of inventive example 5 (with 0.1% of menthol) is 122.2%, and the bioavailability of example 6 (with 2% of menthol) is 119.4%, which proves that the orally disintegrating tablets added with the penetration-promoting flavoring agent in an amount of 0.1% -2% have higher bioavailability.
The dapoxetine hydrochloride orally disintegrating tablet combined with the penetration-promoting corrigent has the characteristics of simple preparation process, low cost, convenient taking and quick response to male premature ejaculation indications. The dapoxetine hydrochloride orally disintegrating tablet disclosed by the invention is combined with 0.1% -2% of a penetration-promoting corrigent, so that the taste of the tablet is improved, the stability of the tablet is improved, the absorption of the tablet is further increased, the maximum plasma concentration (Cmax) is reached within 0.5-1 hour after the tablet is orally taken, the onset time is remarkably accelerated, and the bioavailability is remarkably improved.
Claims (10)
1. The dapoxetine hydrochloride orally disintegrating tablet comprises the following specific components in percentage by weight:
20-40% of dapoxetine hydrochloride
30 to 60 percent of filling agent
5 to 15 percent of disintegrating agent
3 to 10 percent of dry adhesive
Penetration-promoting correctant 0.1-2%
0.5 to 4 percent of lubricant
Wherein the penetration-promoting correctant is menthol or nerolidol;
the dapoxetine hydrochloride orally disintegrating tablet has the weight of 100 mg-200 mg and the hardness of 20N-60N.
2. The dapoxetine hydrochloride orally disintegrating tablet of claim 1, wherein: the filler is one or more of lactose, microcrystalline cellulose, sorbitol, mannitol, and xylitol.
3. The dapoxetine hydrochloride orally disintegrating tablet of claim 2, wherein: the bulking agent is preferably mannitol, and the mannitol is direct-pressure mannitol.
4. The dapoxetine hydrochloride orally disintegrating tablet of claim 1, wherein: the disintegrating agent is one or more of croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, calcium carboxymethyl cellulose and sodium carboxymethyl cellulose.
5. The dapoxetine hydrochloride orally disintegrating tablet of claim 4, wherein: the disintegrant is preferably crospovidone or croscarmellose sodium or a mixture thereof.
6. The dapoxetine hydrochloride orally disintegrating tablet of claim 1, wherein: the dry adhesive is methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvidone, and ethyl cellulose.
7. The dapoxetine hydrochloride orally disintegrating tablet of claim 6, wherein: the dry binder is preferably hydroxypropyl cellulose.
8. The dapoxetine hydrochloride orally disintegrating tablet according to claim 1, wherein the lubricant is one or more of magnesium stearate, sodium stearyl fumarate, aerosil and talc.
9. A preparation method of dapoxetine hydrochloride orally disintegrating tablets is characterized by comprising the following steps:
(1) respectively sieving the raw materials and the auxiliary materials with a 80-mesh sieve for later use;
(2) uniformly mixing the bulk drugs, the filler, the disintegrant and the dry adhesive according to the prescription amount to obtain premixed powder;
(3) adding the penetration-promoting flavoring agent and the lubricant in the prescribed amount into the premixed powder obtained in the step (2), and uniformly mixing to obtain total mixed powder;
(4) and tabletting the total mixed powder by adopting a direct pressing process.
10. Use of dapoxetine hydrochloride orally disintegrating tablets according to any of claims 1 to 9 for the manufacture of a medicament for the treatment of premature ejaculation.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115444827A (en) * | 2021-06-08 | 2022-12-09 | 南京科默生物医药有限公司 | Pharmaceutical composition and preparation method thereof |
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| CN115444827A (en) * | 2021-06-08 | 2022-12-09 | 南京科默生物医药有限公司 | Pharmaceutical composition and preparation method thereof |
| CN115444827B (en) * | 2021-06-08 | 2024-04-23 | 南京科默生物医药有限公司 | Pharmaceutical composition and preparation method thereof |
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