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100, Yongdang Dong, Nam Ku, Busan 608-739, Korea

*Department of Advanced Organic Materials Engineering, Chonbuk National University, 664-14, Dukjin Ku, Jeonju 561-756, Korea

**Nanobiomaterials Laboratory, Korea Research Institute of Chemical Technology, P. O. Box 107, Yuseong, Daejon 305-343, Korea

(Received February 14, 2005;accepted April 8, 2005)

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Abstract:Osmotic granule system which is one of the drug delivery systems has been developed to improve manu- facturing process and other problems of tablet osmotic systems. It consists of water swellable seed layer, nifedipine drug layer, and drug release controlled membrane layer and manufactured by fluidized bed coater. The granule size and mem- brane thickness can be controlled by various amounts of seed and coating solution, respectively. It could be observed that the morphology of osmotic granule was different at each coating step as well as type of coating solution. The bigger the size of granule, the slower the release rate was observed due to decreasing the total specific surface area of granule. Also, it was observed that the increase of membrane thickness was caused to retard the dissolution of nifedipine due to decreasing the water absorption rate. The drug solubility for dissolution media is greatly affected to nifedipine release. From these results, we assured that osmotic granule can be fabricated by fluidized bed coating methods, and the appropriate release profile could be controlled by the controlling of bead size, membrane thickness and dissolution media.

Keywords: osmotic drug delivery system, granulation, fluidized bed coating.

†To whom correspondence should be addressed.

E-mail: [email protected]

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Table 1. The Formulations of Nifedipine Controlled Release Bead Ratio (%)

Ingredients

Seed DrugI^a1 DrugII^a2 MembraneI^b1 MembraneII^b2 Sugar sphere 19.01

Seed 16.98 9.28

Drug layer 13.21 23.33

Lactose 12.67 10.61 11.59 Fructose 3.16 3.71 4.06 HPMC 606 1.26

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KCl 1.53 0.42 0.46

SiO2 0.28 0.37 0.41

PEG 6000 0.25 0.32 0.35

PEG 200 0.56 0.49

Nifedipine 3.71 4.06

Glycerol 0.56 0.49

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TEC 0.08 0.07

Water 17.42 12.73 13.91 0.75 0.66

Ethanol 12.73 17.83 19.48 7.45 6.58

Acetone 31.67 31.83 34.78 74.53 65.85

Total 100.00 100.00 100.00 100.00 100.00

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Dissolution media Artificial serum

Tween80 (1 w/v%)

Artificial serum

SDS (1 w/v%)

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Table 2. The Coating Conditions of Nifedipine Controlled Release Bead

Condition

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Inlet temperature 27»42 ×

Inlet air pressure 2.0»2.1 Torr

Spray air 1.2»2.4 Torr

Flow 14»18 ml/m

Partition height 15 mm

Figure 1. Structure of osmotic controlled release granule, (A) membrane, (B) nifedipine drug layer, (C) swellable polymer layer, and (D) sugar sphere.

+D,#

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membrane, and (E) bead coated by 3% membrane(original magnificationÜ%50).

(A) (B) Figure 4. The mechanism of drug release from the osmotic granule, (A) before dissolution and (B) during dissolution.

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Figure 5. The effect of different size of nifedipine bead on release profile.

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