YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Development of Multiparticulate-system Composed of Sustained Release-microspheres of Pseudoephedrin${\cdot}$HCI and Immediate Release-pellets of Terfenadine Using Solvent Evaporation Method and Spherically Agglomerated Crystallization Process

수용성 염산슈도에페드린과 난용성 테르페나딘의 구형정석조립법과 액중미립구법을 이용한 서방성펠렛 복합제제의 개발

  • Rhee, Gye-Ju (College of Pharmacy Chung-nam National University) ;
  • Do, Ki-Chan (College of Pharmacy Chung-nam National University) ;
  • Kim, Eun-Hee (College of Pharmacy Chung-nam National University) ;
  • Park, Jong-Bum (College of Pharmacy Chung-nam National University) ;
  • Whang, Sung-Joo (College of Pharmacy Chung-nam National University)
  • Published : 1997.06.01
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Abstract

Sustained release-microspheres and immediate release-pellets were prepared to develop a controlled release multiparticulate system containing both water soluble and insoluble dr ug. Pseudoephedrin.HCl (EPD) and terfenadine (TRF) were used as model drugs, respectively. Sustained release-EPD microspheres were prepared by solvent evaporation method using Eudragit RL or RS as a matrix combined with pH-insensitive film coating. Smaller EPD microspheres were obtained when smaller amount of Eudragit as a matrix material or larger amount of magnesium stearate as a dispersing agent was used. However the obtained microspheres did not show syfficient sustained release characteristics. About 97% of EPD was released after 1 hr irrespective of matrix material used. Subsequent coating of the microspheres with pH-insensitive polymer such as Eudragit RS or ethylcelulose (EC) resulted good sustained in 37.5, 73.3 and 92.0% release of encapsulated EPD in distilled water after 1, 3 abd 7 hr, respectively. It corresponds to mean dissolution time (MDT) of 2.3 hr, which is much larger than that of un-coated EPD microspheres (0.0048 hr). Immediate release TRF pellets were prepared by spherically agglomerated crystallization using Eudragit E as an inert matrix and methylene chloride as a liquid binder. Using Eudragit E alone as a matrix resulted in satisfactory physical properties of the pellets such as sphericity, surface texture and flowability, but led to slower release of TRF from pellets than un-modified TRF powder (MDT of 1.70 vs 1.43 hr in pH 1.2 dissolution medium). Introducing propylene glycol or sodium lauryl sulfate as an emulsifier brought about faster release of TRF from pellets (MDT of 1.14 and 0.95 hr, respectively). In conclusion, microencapsulation by solvent evaporation combined with film coating and spherically agglomerated crystallization were successfully utilized to prepare controlled release multiparticulate system composed of sustained release EPD-microspheres and immediate release TRF pellets.

Keywords

References

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