CN112022810B - Icaritin pharmaceutical composition and preparation method thereof - Google Patents
Icaritin pharmaceutical composition and preparation method thereof Download PDFInfo
- Publication number
- CN112022810B CN112022810B CN201910477668.8A CN201910477668A CN112022810B CN 112022810 B CN112022810 B CN 112022810B CN 201910477668 A CN201910477668 A CN 201910477668A CN 112022810 B CN112022810 B CN 112022810B
- Authority
- CN
- China
- Prior art keywords
- icariin
- preparation
- pharmaceutical composition
- solid dispersion
- physical mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
Abstract
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an epimedium aglycone pharmaceutical composition and a preparation method thereof. The preparation method of the icariin pharmaceutical composition comprises the following steps: firstly, the icariin is prepared from icariin and copovidone (PVP/VA), polyethylene glycol and triethyl citrate by adopting a hot-melt extrusion technology, and then the icariin solid dispersion is uniformly mixed with pharmaceutically acceptable auxiliary materials to prepare the preparation. The icariin pharmaceutical composition prepared by the invention improves the solubility and in-vitro dissolution rate of the icariin; in addition, the icariin pharmaceutical composition prepared by the invention has stable process and controllable quality, and is convenient for industrial production.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an anhydroicaritin pharmaceutical composition and a preparation method thereof.
Background
The icaritin is a polyhydroxy flavonoid monomer component in herba Epimedii of Epimedium of berberidaceae. The chemical structural formula is as follows:
pharmacological research shows that the icariin has stronger osteoporosis resisting effect than other flavonoid glycoside compounds in epimedium, has the effects of promoting osteoblast activity and inhibiting osteoclast activity in vitro, and has good application prospect. However, icaritin has poor solubility, the solubility in water is less than 1 mu g/ml, and the icaritin is insoluble or almost insoluble in buffer solutions with different pH values, so that the icaritin is poor in oral absorption and low in bioavailability, the drug effect of the icaritin is limited, and no related preparation is available on the market at present.
CN101485630B discloses an icariin liposome, which contains soybean phospholipid and cholesterol, improves the defect of low bioavailability of icariin, but has low yield and is not easy to be produced in an enlarged way.
CN101513388A discloses a microemulsion of icariin and its preparation method, which dissolves the active ingredient in grease and adds a large amount of emulsifier and co-emulsifier. Although the defect of low bioavailability of the icariin is overcome, a large amount of added surfactant causes great toxic and side effects on a human body.
CN101637467A discloses an icariin or cyclo-icariin phospholipid compound, which greatly improves the solubility of icariin, but has potential safety hazards such as oxidation of lysophospholipid and phospholipid.
The pharmaceutical research of the icaritin capsule reports an icaritin capsule in the literature, and the preparation of a solid dispersion by respectively adopting a melting method and a solvent method by using icaritin and carrier polymers (P188, PEG4000, HP-P-CD, PEG6000, PVP K30, PVP K90, Co-PVP and SOLUPLUPLUS)) is listed, and the preparation of the solid dispersion by adopting the melting-solvent method and the P188 is determined to be the optimal formula process through single factor investigation, so that the in-vitro dissolution rate of the icaritin is remarkably improved, but an organic solvent is used in the preparation process, and the rotary evaporation process is not easy for industrial amplification production.
In summary, the icariin preparation prepared by the prior art has the defects of low bioavailability, large toxic and side effects on human bodies caused by using a large amount of surfactants, organic solvents and the like in the preparation process, difficulty in scale-up production and the like, and therefore, the icariin pharmaceutical composition needs to be provided to overcome the defects.
Disclosure of Invention
In view of the defects of the prior art, the invention provides the icariin pharmaceutical composition and the preparation method thereof, which improve the solubility and the in vitro dissolution rate of the icariin pharmaceutical composition and can realize the preparation process of continuous industrial mass production. Therefore, the inventor adopts a hot-melt extrusion technology which has simple process, high automation degree, no use of organic solvent and is suitable for continuous industrial mass production to prepare the icariin solid dispersion, and then the icariin solid dispersion is mixed with pharmaceutically acceptable auxiliary materials to prepare the preparation.
Specifically, the invention is realized by the following modes:
the invention provides an icariin solid dispersion which is prepared from icariin, copovidone, polyethylene glycol and triethyl citrate by adopting a hot-melt extrusion technology.
Preferably, the weight ratio of the icariin to the copovidone, the polyethylene glycol and the triethyl citrate is 1 (0.5-1.5): (0.5-1.5): 0.07-0.15), more preferably 1 (0.8-1.2): 0.1-0.12, and still more preferably 1:1:1: 0.1.
Preferably, the icariin solid dispersion can be further prepared into preparations such as tablets, capsules and granules.
Preferably, the molecular weight of the polyethylene glycol is 2000-.
The invention also provides an icariin pharmaceutical composition, which contains a solid dispersion prepared from icariin and copovidone, polyethylene glycol and triethyl citrate by adopting a hot-melt extrusion technology, and also contains pharmaceutically acceptable auxiliary materials, wherein the pharmaceutically acceptable auxiliary materials comprise a filler, a disintegrant and a glidant.
Preferably, in the icariin pharmaceutical composition, the icariin solid dispersion accounts for 40-80 parts by weight, the filler accounts for 20-50 parts by weight, the disintegrant accounts for 1-5 parts by weight, and the glidant accounts for 0.1-3 parts by weight.
The filler is preferably, but not limited to, one or more of lactose monohydrate, microcrystalline cellulose, mannitol, and corn starch.
The disintegrant is preferably but not limited to one or more of croscarmellose sodium, crospovidone, sodium carboxymethyl starch, and pregelatinized starch.
The glidant is preferably but not limited to one or more of magnesium stearate, talcum powder, superfine silica gel powder and sodium lauryl sulfate.
The invention also provides a method for preparing the icariin pharmaceutical composition, which comprises the following steps:
(1) evenly mixing icariin, polyethylene glycol and triethyl citrate to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 100-140 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips by the screw to obtain a solid dispersion;
(4) and (4) uniformly mixing the solid dispersion obtained in the step (3) with a filling agent, a disintegrating agent and a glidant to prepare the preparation.
Compared with the prior art, the invention has the following advantages:
(1) the icariin pharmaceutical composition is prepared by selecting copovidone, polyethylene glycol and triethyl citrate to prepare the icariin solid dispersion based on that the medicine can be dissolved in the molten state of polyethylene glycol with the molecular weight of 2000-20000 daltons, and hydrogen bonds formed between the medicine and the polyethylene glycol molecules can increase the thermal stability of the icariin, so that the high dispersibility of the medicine in a carrier is ensured, and the dissolution rate and the stability of the medicine are increased;
(2) the preparation method of the icariin pharmaceutical composition adopts a hot-melt extrusion technology, and realizes the advantages of uniform dispersion of the drug in the carrier material, no organic solvent, no dust, continuous operation, good reproducibility and the like through the processes of melting, dissolving, screw shearing and extruding.
Detailed Description
The following examples further illustrate the benefits of the present invention, and the specific examples are for illustrative purposes only and do not limit the scope of the present invention. And variations and modifications obvious to those skilled in the art in light of the present disclosure are intended to be included within the scope of the present invention.
Example 1
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG6000 and triethyl citrate according to the formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (I) according to the formula, uniformly mixing with lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate, and directly tabletting the powder to obtain the icariin tablet.
Example 2
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG4000 and triethyl citrate according to the formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 100 ℃, adding the physical mixture B obtained in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin capsule
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (I) according to the formula, uniformly mixing with lactose monohydrate, sodium carboxymethyl starch and talcum powder, and filling the powder into capsules to obtain the icariin capsules.
Example 3
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG5000 and triethyl citrate according to the formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 110 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (one) according to the formula, uniformly mixing with microcrystalline cellulose, croscarmellose sodium and superfine silica gel powder, and directly tabletting the powder to obtain the icariin tablet.
Example 4
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG3000 and triethyl citrate according to the formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to 130 ℃, adding the physical mixture B obtained in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) epimedium aglycone tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (one) according to the formula, uniformly mixing with mannitol, crospovidone and sodium dodecyl sulfate, and directly tabletting the powder to obtain the icariin tablet.
Example 5
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG8000 and triethyl citrate according to the formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 140 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin capsule
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (one) according to the formula, uniformly mixing with the pregelatinized starch, the corn starch and the silicon dioxide, and encapsulating the powder to obtain the icariin capsule.
Example 6
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG10000 and triethyl citrate according to the formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (one) according to the formula, uniformly mixing with sucrose, low-substituted hydroxypropyl cellulose and silicon dioxide, and directly tabletting the powder to obtain the icariin tablet.
Example 7
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG15000 and triethyl citrate according to the formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (one) according to the formula, uniformly mixing with microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate, and directly tabletting the powder to obtain the icariin tablet.
Example 8
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG20000 and triethyl citrate according to formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (I) according to the formula, uniformly mixing with lactose monohydrate, corn starch and magnesium stearate, and directly tabletting the powder to obtain the icariin tablet.
Example 9
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG6000 and triethyl citrate according to the formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (one) according to the formula, uniformly mixing with mannitol, crospovidone and micropowder silica gel, and directly tabletting the powder to obtain the icariin tablet.
Comparative example 1
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG6000 and triethyl citrate according to the formula amount to prepare a physical mixture A;
(2) uniformly mixing poloxamer 188 with the physical mixture A according to the formula amount to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (I) according to the formula, uniformly mixing with lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate, and directly tabletting the powder to obtain the icariin tablet.
Comparative example 2
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PVP K30 and triethyl citrate according to formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (I) according to the formula, uniformly mixing with lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate, and directly tabletting the powder to obtain the icariin tablet.
Comparative example 3
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
(1) evenly mixing icariin, PEG6000 and poloxamer 188 according to the formula quantity to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) and (3) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture B obtained in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (I) according to the formula, uniformly mixing with lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate, and directly tabletting the powder to obtain the icariin tablet.
Comparative example 4
Preparation of solid Dispersion
The formula is as follows:
icaritin 10g
PEG6000 10g
Triethyl citrate 1g
The preparation process comprises the following steps:
(1) evenly mixing icariin, PEG6000 and triethyl citrate according to the formula amount to prepare a physical mixture A;
(2) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture A obtained in the step (1) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (I) according to the formula, uniformly mixing with lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate, and directly tabletting the powder to obtain the icariin tablet.
Comparative example 5
Preparation of solid Dispersion
The formula is as follows:
icaritin 10g
Co-polyvidone 10g
Triethyl citrate 1g
The preparation process comprises the following steps:
(1) evenly mixing the icariin and the triethyl citrate according to the formula amount to prepare a physical mixture
Compound A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (I) according to the formula, uniformly mixing with lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate, and directly tabletting the powder to obtain the icariin tablet.
Comparative example 6
Preparation of solid Dispersion
The formula is as follows:
icaritin 10g
Co-polyvidone 10g
PEG6000 10g
The preparation process comprises the following steps:
(1) evenly mixing icariin and PEG6000 according to the formula amount to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the formula amount with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 120 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips through the screw.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (I) according to the formula, uniformly mixing with lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate, and directly tabletting the powder to obtain the icariin tablet.
Comparative example 7
Preparation of solid Dispersion
The formula is as follows:
the preparation process comprises the following steps:
weighing copovidone, adding 60mL of ethanol, and stirring for dissolving; weighing PEG6000 and triethyl citrate, heating in 55 deg.C water bath to melt, adding icariin to dissolve, slowly adding copovidone solution while stirring, mixing, rotary evaporating to remove residual solvent, rapidly solidifying, pulverizing, sieving with 80 mesh sieve, and storing in a drier in dark place.
Preparation of (II) icariin tablets
The formula is as follows:
the preparation process comprises the following steps:
weighing the icariin solid dispersion prepared in the step (I) according to the formula, uniformly mixing with lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate, and directly tabletting the powder to obtain the icariin tablet.
Comparative example 8
Preparation of icaritin tablet
The formula is as follows:
the preparation process comprises the following steps:
evenly mixing the icariin, the copovidone, the PEG6000, the lactose monohydrate, the microcrystalline cellulose, the sodium carboxymethyl starch and the magnesium stearate according to the prescription amount, and directly tabletting.
Comparative example 9
Preparation of icaritin capsule
The formula is as follows:
icaritin 10g
Poloxamer 18840 g
Silica gel micropowder 1g
The preparation process comprises the following steps:
preparing an icariin solid dispersion by adopting a melting-solvent method, weighing icariin, adding 50mL of ethanol, and stirring for dissolving; weighing poloxamer 188, heating in a water bath kettle at 55 deg.C to melt, slowly pouring into icariin solution while stirring, mixing, rotary evaporating to remove residual solvent, rapidly solidifying, pulverizing, sieving with 80 mesh sieve, mixing with glidant micropowder silica gel, and making into capsule.
Comparative example 10
(1) Preparation of icaritin phospholipid complex
The formula is as follows:
icaritin 20g
Soybean lecithin 40g
The preparation process comprises the following steps:
weighing icariin and soybean phospholipid, adding 500mL of ethanol, refluxing at 50 ℃ for 1h until the reaction liquid is clear, performing rotary evaporation to remove the solvent to obtain a yellow solid, and crushing and sieving to obtain the icariin phospholipid complex.
(2) Preparation of icaritin capsule
The formula is as follows:
the preparation process comprises the following steps:
and (2) adding lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate into the icariin phospholipid complex prepared in the step (1), uniformly mixing and encapsulating.
Verification of the examples: the equilibrium solubility, in vitro dissolution rate and related substance determination of the icariin pharmaceutical composition are carried out.
(1) Equilibrium solubility test: using water, 0.2% Tween 80 water solution, pH6.8 phosphate buffer solution (containing 0.2% Tween) as medium to react with icariin; solid dispersions prepared in examples 1-9 and comparative examples 1-6, 8; the phospholipid complexes prepared in comparative example 9 were subjected to an equilibrium solubility test, and the results are shown in Table 1.
TABLE 1 Epimedium aglycone raw material, solid dispersions prepared in examples 1-9 and comparative examples 1-6, 8 and capsule prepared in comparative example 9 Balanced solubility results (ug/ml)
From the above results, it is known that icaritin is a poorly soluble drug that is insoluble in water and phosphate buffer at ph6.8, and that preparation of icaritin into a solid dispersion and a phospholipid complex by different techniques can increase equilibrium solubility of icaritin in the above media. The solid dispersions prepared in examples 1 to 9 showed a significant increase in equilibrium solubility compared to the solid dispersions prepared in comparative examples 1 to 6 and 8. Comparative example 9 preparation of icariin into a phospholipid complex greatly improves the solubility in water, but the phospholipid complex does not greatly improve the solubility of icariin in phosphate buffer solution and surfactant-containing medium at ph6.8 due to the action of ions or surfactants in the medium.
(2) Dissolution test in vitro: referring to the dissolution method of the icaritin capsule in the literature data of 'pharmaceutical research of the icaritin capsule', the determination method is as follows: according to the first method (basket method) of appendix of the second part of the 'Chinese pharmacopoeia' 2015 edition, 900mL of phosphate buffer solution (containing 0.2% of Tween 80) with pH6.8 is used as a dissolution medium, the rotating speed is 75rpm, the temperature is 37 +/-0.5 ℃, 5mL of the dissolution medium is sampled at 45min, 5mL of the fresh dissolution medium at the same temperature is supplemented, the sample is filtered by a 0.45-micron microporous membrane, and a primary filtrate is discarded to obtain a test solution; and accurately weighing 20mg of the icariin reference substance, placing the icariin reference substance in a 50mL measuring flask, adding absolute ethyl alcohol to dissolve and dilute the icariin reference substance to scale, accurately weighing 2.5mL of the icariin reference substance, placing the icariin reference substance in a 20mL measuring flask, adding a dissolution medium to dilute the icariin reference substance to scale, and shaking up the icariin reference substance to obtain reference substance solution. The dissolution rate of the icariin capsule or tablet is measured by a High Performance Liquid Chromatography (HPLC) method, and the dissolution rate is calculated by the peak area according to an external standard method. The dissolution test results are shown in Table 2.
TABLE 2 results of 0-day and 6-month accelerated (40 ℃ C.) dissolution (%) of each icaritin preparation
As can be seen from the above results, the dissolution rates of the preparations prepared in examples 1 to 9 are all greater than 90%, and the dissolution rates have no significant change after the preparations are placed for 6 months under the accelerated condition, while the dissolution rates are significantly reduced after the preparations are placed for 6 months under the accelerated condition in comparative examples 1 to 10.
(3) The related substance detection method comprises the following steps: measured according to high performance liquid chromatography (2015 version of Chinese pharmacopoeia 0512, four parts of general rules). Octadecylsilane chemically bonded silica was used as a filler, and the mixture was mixed with 0.1% phosphoric acid solution: acetonitrile (25:75) is used as a mobile phase, the flow rate is 1.0ml/min, the sample amount is 10ul, the column temperature is 30 ℃, and the detection wavelength is 270 nm. The number of theoretical plates is not less than 5000 calculated according to the icariin peak, and the separation degree of the icariin peak and the adjacent impurity peak is in accordance with the requirement. The results of the substance detection are shown in Table 3.
TABLE 3 detection results of related substances in icariin preparation
As can be seen from the above results, the substances of examples 1 to 9 were significantly lower than those of comparative examples 1 to 9, and the substances of comparative examples 1 to 10 were significantly changed after the storage under accelerated conditions for 6 months, while the substances of comparative examples 1 to 9 were significantly changed after the storage under accelerated conditions for 6 months.
The inventor adopts other auxiliary materials which are conventional in the art and the icariin solid dispersion to be protected to prepare the medicinal preparation according to the conventional technology, and the results similar to the dissolution and related substances are obtained.
Claims (7)
1. A icariin solid dispersion is characterized in that: the modified drug is prepared from epimedium aglycone, copovidone, polyethylene glycol and triethyl citrate by adopting a hot-melt extrusion technology, wherein the weight ratio of the epimedium aglycone to the copovidone to the polyethylene glycol to the triethyl citrate is 1 (0.1-2) to (0.1-3) to (0.05-0.3), and the molecular weight of the polyethylene glycol is 2000-20000 daltons.
2. An icaritin pharmaceutical composition comprising the icaritin solid dispersion of claim 1, wherein: the tablet also contains pharmaceutically acceptable auxiliary materials, wherein the pharmaceutically acceptable auxiliary materials comprise a filling agent, a disintegrating agent and a glidant.
3. The icaritin pharmaceutical composition of claim 2, wherein: the weight parts of the icariin solid dispersion in the composition are 40-80, the weight parts of the filler are 20-50, the weight parts of the disintegrant are 1-5 and the weight parts of the glidant are 0.1-3.
4. The icaritin pharmaceutical composition according to claim 2 or 3, wherein: the filler is selected from one or more of lactose monohydrate, microcrystalline cellulose, mannitol and corn starch.
5. The icaritin pharmaceutical composition according to claim 2 or 3, wherein: the disintegrant is selected from one or more of croscarmellose sodium, crospovidone, sodium carboxymethyl starch and pregelatinized starch.
6. The icaritin pharmaceutical composition according to claim 2 or 3, wherein: the glidant is selected from one or more of magnesium stearate, talcum powder, superfine silica gel powder and sodium dodecyl sulfate.
7. A method for preparing the icariin pharmaceutical composition of claim 2, comprising the steps of:
(1) evenly mixing icariin, polyethylene glycol and triethyl citrate to prepare a physical mixture A;
(2) uniformly mixing the copovidone with the physical mixture A to prepare a physical mixture B;
(3) setting the extrusion temperature of the double-screw hot-melt extruder to be 100-140 ℃, adding the physical mixture B in the step (2) into the extruder after the preset temperature is reached, carrying out melting-dissolving-mixing, starting the screw after the melting is completed, and extruding strips by the screw to obtain a solid dispersion;
(4) and (4) uniformly mixing the solid dispersion obtained in the step (3) with a filling agent, a disintegrating agent and a glidant to prepare a preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910477668.8A CN112022810B (en) | 2019-06-03 | 2019-06-03 | Icaritin pharmaceutical composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910477668.8A CN112022810B (en) | 2019-06-03 | 2019-06-03 | Icaritin pharmaceutical composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112022810A CN112022810A (en) | 2020-12-04 |
| CN112022810B true CN112022810B (en) | 2022-05-24 |
Family
ID=73576201
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910477668.8A Active CN112022810B (en) | 2019-06-03 | 2019-06-03 | Icaritin pharmaceutical composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112022810B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113368066B (en) * | 2020-03-10 | 2024-03-15 | 鲁南制药集团股份有限公司 | Icariin tablet and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016110173A1 (en) * | 2015-01-08 | 2016-07-14 | 吉林省帝医生物科技有限公司 | New inhibitor for influenza virus neuraminidase and uses thereof |
| CN105982869A (en) * | 2015-02-03 | 2016-10-05 | 山东新时代药业有限公司 | Anhydroicaritin tablet |
-
2019
- 2019-06-03 CN CN201910477668.8A patent/CN112022810B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016110173A1 (en) * | 2015-01-08 | 2016-07-14 | 吉林省帝医生物科技有限公司 | New inhibitor for influenza virus neuraminidase and uses thereof |
| CN105982869A (en) * | 2015-02-03 | 2016-10-05 | 山东新时代药业有限公司 | Anhydroicaritin tablet |
Non-Patent Citations (3)
| Title |
|---|
| 淫羊藿素-泊洛沙姆188 固体分散体的制备及溶出度研究;吴玲;《中国药房》;20151231;第26卷(第19期);第2702-2704页 * |
| 淫羊藿苷固体分散体的制备及其体外溶出研究;赵君怡等;《中国现代中药》;20070216(第02期);第18-20页 * |
| 热熔挤出技术制备泊沙康唑固体分散体及其体外评价;朱丽 等;《中国药科大学学报》;20151231;第46卷(第3期);第309-315页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112022810A (en) | 2020-12-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Shah et al. | Development of novel microprecipitated bulk powder (MBP) technology for manufacturing stable amorphous formulations of poorly soluble drugs | |
| EP2589384A1 (en) | New Pharmaceutical Compositions for the Treatment of Hyper-Proliferative Disorders | |
| CN102988296A (en) | Celecoxib solid dispersion and preparation method thereof | |
| EP2165702B1 (en) | Stable and readily dissolved compositions of candesartan cilexetil prepared with wet granulation | |
| CN101095670A (en) | Luteolin phospholipid complexes and method for preparing the same and application thereof | |
| CN112022810B (en) | Icaritin pharmaceutical composition and preparation method thereof | |
| WO2007086689A1 (en) | A solid dispersion comprising ubidecarenone, a process for preparing the same and a pharmaceutical composition comprising the same | |
| EP2050436A1 (en) | Pharmaceutical composition containing dutasteride | |
| CN111184699A (en) | Nifedipine controlled release capsule and preparation method thereof | |
| CN110711176A (en) | Cilnidipine nanosuspension and preparation method thereof | |
| CN106511348A (en) | Huperzine-A framework particles, orally disintegrating tablets and preparation methods thereof | |
| CN106309395A (en) | Tacrolimus sustained-release tablets and preparation method thereof | |
| CN117769412A (en) | Poorly soluble drug osmotic pump controlled release tablet and preparation method thereof | |
| JPH04159222A (en) | Production of solid preparation for oral administration | |
| CN104415034A (en) | Imidafenacin pharmaceutical composition and preparation method thereof | |
| JP6072705B2 (en) | Solid dispersion formulation | |
| CN113577032A (en) | Preparation method of tacrolimus solid dispersion, quick-release pharmaceutical composition and application | |
| CN105412021B (en) | Hot-melt extruded method prepares ginkolide B amorphous solid dispersion | |
| CN112245397A (en) | Dacotinib quick-release preparation and preparation method thereof | |
| KR20030095600A (en) | Controlled release composition comprising felodipine, and method of the preparing thereof | |
| CN112076190A (en) | Solid preparation containing insoluble thienopyridine composition and preparation method thereof | |
| CN113368066B (en) | Icariin tablet and preparation method thereof | |
| CN106913542B (en) | Prasugrel tablet and preparation method thereof | |
| KR20060015570A (en) | Microcrystal | |
| CN116019815A (en) | Cefditoren pivoxil pharmaceutical composition and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |