CN103751151A - Venlafaxine slow-release formulation capable of providing 24-h release result and preparation method of venlafaxine slow-release formulation - Google Patents
Venlafaxine slow-release formulation capable of providing 24-h release result and preparation method of venlafaxine slow-release formulation Download PDFInfo
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- CN103751151A CN103751151A CN201310748664.1A CN201310748664A CN103751151A CN 103751151 A CN103751151 A CN 103751151A CN 201310748664 A CN201310748664 A CN 201310748664A CN 103751151 A CN103751151 A CN 103751151A
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Abstract
The invention belongs to the field of pharmaceutical preparations, and discloses a slow-release formulation of venlafaxine hydrochloride. The formulation is composed of a piller containing venlafaxine hydrochloride and a slow-release coating layer attached in the outer layer; the preparation disclosed by the invention is capable of enabling a medicine to release continuously and stably within 24 h; steady blood concentration is kept; the drug administration frequency of patients is reduced; the drug administration safety and the patient compliance are improved; the preparation process is simple and practicable; the venlafaxine slow-release formulation disclosed by the invention is applied to industrial production.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of antidepressants slow release capsule preparation and preparation method thereof, relate to venlafaxine sustained-release capsule and preparation method thereof.
Background technology
Venlafaxine (Venlafaxine), is a kind of novel antidepressant with unique chemical characteristic and neuropharmacology effect, is also a kind of effectively antianxiety drugs.Venlafaxine is used with the form of hydrochlorate, its chemistry (R/S)-1-[2-(dimethylamine)-1-(4-anisyl) ethyl by name] Hexalin hydrochlorate, its clinical effectiveness is obviously better than the antidepressants of other classifications, it is the representative medicine of SNRI class (5-hydroxy tryptamine, norepinephrine inhibitor).When venlafaxine is used with regular pharmaceutics, due to its rapidly-soluble character, after administration, in the short time, can reach higher blood drug level, then decline rapidly, cause thus patient to need repeatedly take medicine every day, and because causing most of patient, the peak valley behavior of this violent blood drug level produces side effect nauseating, vomiting, so, made can sustained release medicine form of administration be very favorable, the sustained release of its active component produces lower and blood drug level stably, can reduce side effect, improve patient's compliance.
The form of sustained release administration has multiple, and the most useful and to be convenient to industrialized form be most the medicine that comprises medicine carrying micropill.The drug release behavior that micropill is made slow releasing preparation is the summation of each piller drug release behavior of a dosage of composition, the error of indivedual pillers in preparation or the failure discharging in vivo are all unlikely to the drug release behavior of overall preparation to produce and have a strong impact on, thereby have guaranteed the safety of curative effect of medication and medication.The slow releasing preparation that the present invention embodies can 24 hours sustained release medicines, be that patient only needs to take every day once, can effectively improve the phenomenon that occurs sharp-pointed value and minimum (crest and trough) because repeatedly taking blood drug level that VENLAFAXINE HCL capsule or tablet cause every day.
The preparation method that the present invention embodies was prepared medicine carrying micropill based on extruding spheronization technique before this, afterwards based on fluidized bed coating technology bundled slow-releasing clothing layer, and in this slow release layer, had added innovatively the porogen with the effect of remarkable control rate of release.Method prepared by micropill has a variety of, is mainly based on following several principles: extruding-nodularization, centrifugal granulator, fluidisation rotation are granulated and high shear mixing.At present comparatively general and conventional is aborning that extruding-nodularization legal system is for micropill, utilization extrudes that micropill product prepared by spheronization has epigranular, the advantage such as zonation is narrow, roundness good, intensity is high, density is large, smooth surface, can prepare diameter from 0.6mm to 3.5mm within the scope of the micropill of different size, based on this present invention, in micropill preparation process, selected to extrude the preparation that spheronization contains pill core.Then adopt fluidized bed coating technology to wrapping up one deck sustained-release coating layer containing pill core.Fluid bed coating of pellets technology has been the preparation process technology of comparative maturity, by adjuvant and the consumption thereof selecting different coating materials and there is miscellaneous function, reach different coating objects, adopt fluidization coating have coating efficiency high, effective, can reappear, can industrialization etc. advantage.
Summary of the invention
The object of the present invention is to provide a kind of sustainable administration, simple for process, and a kind of slow releasing capsule capable of being industrialized.The present invention is applied on inertia spheroid venlafaxine and a kind of bonding agent to form a kind of vertical piller of releasing of medicine carrying, then by adopting the soluble film formed polymer opposition of water to release piller, carries out coating and forms slow-release pill.The speed that medicine discharges from slow-release pill by the thickness of coating and coating form coating particularly form the consumption of porogen control.This slow releasing capsule is by the medicine carrying piller that contains VENLAFAXINE HCL, microcrystalline Cellulose and hypromellose and contain ethyl cellulose and the slow release layer of polyvidone forms.
Wherein, active component is venlafaxine and pharmaceutically acceptable salt thereof, and unit dose is counted 75mg with venlafaxine.
The microcrystalline Cellulose that described medicine carrying piller contains 60～65 parts is as diluent, and the hydroxypropyl cellulose of 0.3～0.7 part forms as adhesive.
It is 8%～11%(using ball core as basis that slow release layer contains weight) ethyl cellulose as the insoluble high molecular polymer of water, and weight is 0.8%～1.1%(take ball core as basis) porogen, wherein porogen is that 0.96%～1.0%(is take ball core as basis as its content preferable range of adjuvant that can be water-soluble membrane permeability be played to key adjusting).
Preparation method comprises the steps:
(1) extrude round as a ball preparation and carry pill core: venlafaxine, the mixing diluents of recipe quantity are even; be equipped with 1% adhesive and account for 35%～40% of material gross weight; stirring makes that humidity and viscosity is applicable to can be used as granulator for spherical particulate and carries out the soft material of extrusion granulator; then the micropill that to make size by specific parameter be 14 to 26 object roundings, compact, preferred size is the micropill between 16 to 24 orders.
(2) fluid bed bundled slow-releasing clothing layer: the ethyl cellulose of recipe quantity is dissolved in 95% appropriate ethanol to the coating solution of preparation into about concentration 6%, treat to add after ethyl cellulose dissolves completely the porogen of recipe quantity, the coating solution that above-mentioned dissolving is mixed adopts multifunctional fluidized bed spray coating ball core, coating weightening finish 6.0%～7.5%, dry, coating membrane should be even, smooth, fine and close.
(3) filling of capsule preparation: amount to Rapid Dose Calculation loading amount, load capsule and obtain this product.
The present invention adopts and extrudes spheronization preparation year pill core, can avoid using celphere to wrap up the low problem of carrying drug ratio that medicated layer is brought, and be more conducive to the steady release of medicine; The present invention only wraps up one deck sustained-release coating layer, without carrying out multiple coatings, can reach 24 hours sustained release effects, simple for process, and materials kind is few, and formula is simple, utilizes suitability for industrialized production and cost control.The invention belongs to many granules medicine-releasing system simultaneously, its drug release behavior is the summation of each piller drug release behavior of a dosage of composition, with respect to the medicine-releasing system of individual unit as slow releasing tablet, more can avoid risk or other possible risks of burst drug release, thereby guarantee the safety of curative effect of medication and medication.
accompanying drawing explanation:
Fig. 1: embodiment product and commercially available former product (" Efexor XR ") the cumulative release curve chart that grinds.
By accompanying drawing, can be found out, venlafaxine sustained-release preparations provided by the invention and commercially available import be former grinds product and reaches and be close to consistent releasing effect, listing of the present invention proves that its inherent quality has reached the consistent of height with the former commercially available prod of grinding, therefore will make up largely market at home of this kind and grind with import is former the price advantage that formation is larger compared with product.
the specific embodiment:
Following embodiment is in order to the present invention to be described, but do not limit scope of invention.
Embodiment 1:
| Supplementary material title | Dosage (mg) | Percentage by weight (%) |
| Ball core: | ? | ? |
| VENLAFAXINE HCL | 84.37 | 40.09 |
| Microcrystalline Cellulose PH101 | 125.07 | 59.43 |
| Hypromellose | 1.005 | 0.48 |
| Slow release layer: | Dosage (mg) | Percentage by weight (%) |
| Ethyl cellulose 100FP | 13.26 | 5.4 |
| PVP K30 | 1.47 | 0.6 |
| 95% ethanol | 230.8 | 94 |
Preparation technology:
By the VENLAFAXINE HCL of recipe quantity, microcrystalline Cellulose mix homogeneously, hypromellose (E3-LV) is made into 1% adhesive to be added in said mixture and to add to and account for 35%～40% of material gross weight, humidity and the applicable colloidal substance soft material of viscosity are made in stirring, above-mentioned soft material is adopted and extrudes spheronization by extruding, spheronizing dry, obtain the micropill of the not coating that contains medicine.
The ethyl cellulose of recipe quantity is dissolved in 95% appropriate ethanol to the coating solution of preparation into about concentration 6%, treat to add after ethyl cellulose dissolves completely the PVP K30 of recipe quantity, the coating solution that above-mentioned dissolving is mixed adopts multifunctional fluidized bed spray coating ball core, and coating degree is 7.0%(weightening finish ratio).
Above-mentioned coated micropill sieve obtain particle diameter at 14 orders to the micropill between 24 orders, calculate loading amount pack in conventional hard gelatin capsule.
Embodiment 2:
| Supplementary material title | Dosage (mg) | Percentage by weight (%) |
| Ball core: | ? | ? |
| VENLAFAXINE HCL | 84.37 | 40.09 |
| Microcrystalline Cellulose PH101 | 125.07 | 59.43 |
| Hypromellose | 1.005 | 0.48 |
| Slow release layer: | Dosage (mg) | Percentage by weight (%) |
| Ethyl cellulose 100FP | 11.24 | 5.34 |
| PVP K30 | 1.39 | 0.66 |
| 95% ethanol | 230.8 | 94 |
Preparation technology:
By above-mentioned prescription table, the coating that has been to adjust slow release layer with embodiment difference is write out a prescription, and the ratio of porogen increases.Preparation technology is with embodiment 1, and difference is that coating increases weight to 6%.Sieve obtain particle diameter at 14 orders to the micropill between 24 orders, calculate loading amount pack in conventional hard gelatin capsule, gained sample has intimate identical releasing effect similarly to Example 1.
Claims (7)
1. a venlafaxine sustained-release capsule, comprises the micropill of the effective therapeutic dose in capsule shells and softgel shell, it is characterized in that micropill is by forming containing pill core and the sustained release coating layer that uses fluidized bed coating technology to prepare of extruding prepared by spheronization technique.
2. according to slow releasing preparation claimed in claim 1, the pill core that contains wherein comprises venlafaxine and pharmaceutically acceptable salt and pharmaceutically useful diluent and adhesive.
3. according to slow releasing preparation claimed in claim 1, sustained release coating layer wherein comprises as the insoluble macromolecular material of blocker and the porogen for regulating coating membrane permeability to add innovatively.
4. according to slow releasing preparation claimed in claim 1, its preparation method was prepared medicine carrying micropill based on extruding spheronization technique before this, afterwards based on fluidized bed coating technology bundled slow-releasing clothing layer.
5. according to slow releasing preparation claimed in claim 1, it is characterized in that the shared weight ratio of each composition is that VENLAFAXINE HCL is 40.09 parts, diluent is 60～65 parts, and adhesive is 0.3～0.7 part, and blocker is 5.0～5.5 parts, and porogen is 0.5～0.6 part.
6. according to slow releasing preparation claimed in claim 2, it is characterized in that diluent used in ball core is one or more in microcrystalline Cellulose, lactose, dextrin, adhesive therefor is hydroxypropyl cellulose.
7. according to slow releasing preparation claimed in claim 3, it is characterized in that blocker used in sustained-release coating layer is one or more in ethyl cellulose 100FP, 100P, N-100 model; Porogen used is one or more in polyvidone, Polyethylene Glycol, polyvinyl alcohol and sodium lauryl sulphate.
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| CN201310748664.1A CN103751151A (en) | 2013-12-31 | 2013-12-31 | Venlafaxine slow-release formulation capable of providing 24-h release result and preparation method of venlafaxine slow-release formulation |
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| CN201310748664.1A CN103751151A (en) | 2013-12-31 | 2013-12-31 | Venlafaxine slow-release formulation capable of providing 24-h release result and preparation method of venlafaxine slow-release formulation |
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Cited By (4)
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| CN105326814A (en) * | 2015-10-09 | 2016-02-17 | 北京万全德众医药生物技术有限公司 | Topiramate sustained release preparation pharmaceutical composition |
| CN106955276A (en) * | 2017-03-28 | 2017-07-18 | 海南合瑞制药股份有限公司 | A kind of venlafaxine hydrochloride slow-release capsule composition |
| CN108685869A (en) * | 2018-07-26 | 2018-10-23 | 江苏黄河药业股份有限公司 | A kind of clarithromycin capsule |
| CN112402395A (en) * | 2020-10-28 | 2021-02-26 | 海南卫康制药(潜山)有限公司 | Venlafaxine sustained-release capsule composition and preparation process thereof |
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Cited By (5)
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| CN106955276A (en) * | 2017-03-28 | 2017-07-18 | 海南合瑞制药股份有限公司 | A kind of venlafaxine hydrochloride slow-release capsule composition |
| CN106955276B (en) * | 2017-03-28 | 2019-12-13 | 海南合瑞制药股份有限公司 | Venlafaxine hydrochloride sustained-release capsule composition |
| CN108685869A (en) * | 2018-07-26 | 2018-10-23 | 江苏黄河药业股份有限公司 | A kind of clarithromycin capsule |
| CN112402395A (en) * | 2020-10-28 | 2021-02-26 | 海南卫康制药(潜山)有限公司 | Venlafaxine sustained-release capsule composition and preparation process thereof |
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