Patent Application
20070275066
Practical and presently preferred embodiments of the present invention are illustrative as shown in the following Examples and Comparative Examples.
However, it will be appreciated that those skilled in the art, on consideration of this disclosure, may make modifications and improvements within the spirit and scope of the present invention.
1) Coating of Active Ingredient Layer
4.71 wt % of sugar (pellet size: 600-710 μm) was added to a fluidized bed coater and was coated with a composition for forming an active ingredient layer. The composition for forming an active ingredient layer was prepared by dissolving and dispersing 4.71 wt % of corn starch, 4.0 wt % of venlafaxine hydrochloride, 1.41 wt % of Eudragit RS, 0.14 wt % of triethyl citrate, 1.7 wt % of talc, 0.94 wt % of magnesium stearate, 47.08 wt % of dichloromethane, and 35.31 wt % of ethanol. The coating condition was: inlet air pressure=5.8 bar, spray air pressure=1.2 bar, outlet air temperature=28° C., inlet air temperature=30° C., flow rate=12, and outlet air flat=30%.
2) Coating of Sustained Release Layer
47.62 wt % of the coated pellet (850-1000 μm) was coated with a composition for forming a sustained release layer. The composition for forming a sustained release layer was prepared by mixing 9.52 wt % of Eudragit NE30D, 33.34 wt % of purified water, and 9.52 wt % of talc. The coating condition was: inlet air pressure=5.8 bar, spray air pressure=0.6 bar, outlet air temperature=28° C., inlet air temperature=29° C., flow rate=6, and outlet air flat=30%.
1) Coating of Active Ingredient Layer
4.13 wt % of sugar (pellet size: 600-710 μm) was added to a fluidized bed coater and was coated with a composition for forming an active ingredient layer. The composition for forming an active ingredient layer was prepared by dissolving and dispersing 4.95 wt % of venlafaxine hydrochloride, 1.32 wt % of Eudragit RS, 3.30 wt % of cellulose acetate, 1.03 wt % of hydroxypropyl methyl cellulose, 0.46 wt % of dibutyl cebacate, 1.11 wt % of talc, 1.11 wt % of magnesium stearate, 20.65 wt % of acetone, 30.97 wt % of ethanol and 30.97 wt % of dimethyl chloride. The coating condition was: inlet air pressure=5.8 bar, spray air pressure=1.2 bar, outlet air temperature=28° C., inlet air temperature=30° C., flow rate=12, and outlet air flat=30%.
2) Coating of Sustained Release Layer
13.12 wt % of the coated pellet (850-1000 μm) was coated with a composition for forming a sustained release layer. The composition for forming a sustained release layer was prepared by dissolving or dispersing 2.62 wt % of Eudragit RS100, 0.26 wt % of dibutyl cebacate, 1.05 wt % of talc, 0.26 wt % of magnesium stearate, 39.37 wt % of acetone, 39.37 wt % of ethanol, and 3.95 wt % of purified water. The coating condition was: inlet air pressure=5.8 bar, spray air pressure=0.6 bar, outlet air temperature=28° C., inlet air temperature=30° C., flow rate=6, and outlet air flat=30%.
In this Example, EFEXOR *XR (Wyeth) containing venlafaxine hydrochloride as a commercially available antidepressant was used. The EFEXOR *XR was a capsule prepared by mixing venlafaxine hydrochloride with ethyl cellulose, hydroxypropyl methyl cellulose, titanium oxide and iron oxide and comprised 75 mg of venlafaxine per capsule.
For the EFEXOR *XR, dissolution was performed with 900 ml of purified water according to USP method I (Basket, 100 rpm). The dissolution rate was: 30% for 2 hr, 30-55% for 4 hr, 55-80% for 8 hr, 65-90% for 12 hr and 80% or more for 24 hr.
The dissolved amount of the venlafaxine hydrochloride containing granules prepared according to Examples 1 and 2 and venlafaxine of EFEXOR *XR of Comparative Example 1 was analyzed with HPLC under the following conditions. The dissolution rate is shown in Table 1.
Mobile phase: acetonitrile/0.02M phosphate buffer (pH 3.8)=3/7 by volume
Column: SC-04 (125*4.0 mm), PRONTOSIL EUROBOND C18 5.0 μm
Flow rate: 1.0 mL/min
Detector: 229 nm
Dissolution condition: 37.5° C., 900 ml of purified water
As can be seen from Table 1, the sustained release drug delivery systems of Examples 1 and 2 slowly release a drug at a consistent rate for 24 hours, and thus they are very suitable sustained release preparations.
As described above, the sustained release drug delivery system according to the present invention can be simply prepared in a two-staged process by using the pharmacologically active ingredient and the water insoluble polymer together in the active ingredient layer and mass production thereof is possible. In addition, the release rate of a pharmacologically active ingredient can be effectively controlled by varying the type of the water insoluble polymer, the thickness of the active ingredient layer, the type of a sustained release film forming material and the thickness of the sustained release layer.
Those skilled in the art will appreciate that the conceptions and specific embodiments disclosed in the foregoing description may be readily utilized as a basis for modifying or designing other embodiments for carrying out the same purposes of the present invention. Those skilled in the art will also appreciate that such equivalent embodiments do not depart from the spirit and scope of the invention as set forth in the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10-2006-0047682 | May 2006 | KR | national |
