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Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

CN 11-5981/TQ

Postal Subscription Code 80-969

2018 Impact Factor: 2.809

Front. Chem. Sci. Eng.    2014, Vol. 8 Issue (3) : 346-352    https://doi.org/10.1007/s11705-014-1443-9
RESEARCH ARTICLE
Utilizing melt crystallization fundamentals in the development of a new tabletting technology
Ahmed ABOUZEID(),Sandra PETERSEN,Joachim ULRICH()
Martin Luther University Halle-Wittenberg, Center for Engineering Science, Thermal Process Engineering, D-06099 Halle, Germany
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Abstract

Increasing production effeciency and lowering costs are some of the many advantages melt crystallization technology offers over the conventional methodology of tabletting. A normal tablet consists of a pure shell or a coat and a separate core constituting the pharmaceutical active ingredient. Great emphasis is put on the purity of the shell since its purpose is to solely protect and deliver the active ingredient to its target. Melt crystallization is a purification (separation) process. It is discussed here for its ability to produce coated tablets, by separating the “coating” material from the “to be coated” material coming from one molten mixture. Molten drops of lutrol-ibuprofen mixture are produced using the drop forming technique. The subsequent analysis involves proving and quantifying the phase separation (coat purity). The mechanism of a crystallizing drop is shown as direct evidence of the ongoing process. Moreover, solidified tablet batches are analyzed for the purity of their coating by measuring the ibuprofen concentration. This optimization process is carried out through multiple stages of development and condition enhancements in order to produce the most pure tablet coating. As a result, a trial showing an almost purely coated tablet is presented here.

Keywords phase separation      melt crystallization      tablets      process optimization     
Corresponding Author(s): Ahmed ABOUZEID   
Issue Date: 11 October 2014
 Cite this article:   
Ahmed ABOUZEID,Sandra PETERSEN,Joachim ULRICH. Utilizing melt crystallization fundamentals in the development of a new tabletting technology[J]. Front. Chem. Sci. Eng., 2014, 8(3): 346-352.
 URL:  
https://academic.hep.com.cn/fcse/EN/10.1007/s11705-014-1443-9
https://academic.hep.com.cn/fcse/EN/Y2014/V8/I3/346
Fig.1  Successive mixture concentrations melt peaks
Fig.2  The generated binary phase diagram
Fig.3  Series of pictures showing the crystallization of a lauric acid-ibuprofen drop
Fig.4  Series of pictures showing the crystallization of a lutrol-ibuprofen drop
Fig.5  Certain stages are mandatory to account for in the process of tablet development. Each stage poses a challenge to overcome in the process progression
BatchMelt composition (lutrol : ibuprofen)Cooling temperature /°CPower ultrasound intensity /%Seeding
170 : 3020Top
270 : 302010Top
390 : 103010Top
490 : 1040Bed
590 : 1040Starch bed
Tab.1  Application of different conditions to the respective drop batches
Y = 0.0207X
BatchCore concentration /%Coat concentration /%Concentration difference /%
132.9932.740.38
233.4733.140.49
35.794.5512
44.722.5130.6
53.481.9628
Tab.2  Different drop batches prone to different conditions result in different phase separation efficacy
Fig.6  The two circles designate the active ingredient irregularities that pose a challenge against the tablet sampling procedure
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