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Influence of lattice defects upon mixing processes
Powder
Technology.
@ Elsevier Sequoia
Short
22 (1979) 289 - 290 S.A., Lausanne -Printed
289 in the Netherlands
Communication
Influence of Lattice Defects Processes*
R. HtiTENRAUCH
upon Mixing
and I. KEINER
VEB Jenapharm. Research Department, Otto-SchottStrasse 13, 69 Jena (German Democratic Republic)
(Received
October
17,197s)
Mixing of solids represents the most important unit operation in powder technology. According to the results obtained so far, the process is influenced by the folldwing material factors [1 - 51 : particle size, particle size distribution, particle shape, particle density, bulk density, surface roughness, agglomeration tendency (adhesiveness, cohesiveness), flow behaviour and electrostatic charge. Besides this we observed recently, through indirect evidence, that the mixing rate depends upon the degree of order at the solid surface [S] . As is well known, the strength of compacts varies with the incorporation time and with the homogeneity of lubricants in the material. We found that this time effect is determined by the degree of order in the bases. Mechanically activated and imperfect. solids result in a more rapid and more homogeneous distribution of the lowclosed component than non-activated ones. Therefore, lattice defects as active points probably regulate aU interactions at the surface of a solid. Like other phenomena, the interparticular adhesion depends on the degree of order- A more extensive and more intensive adherence may decrease the extent of individual segregation steps and, thereby, increase the ability to homogenize. Lattice defects may function in the same way as low humidity. To confirm the important influence of lattice_ defects, a direct demonstration was undertaken. Using constant mixing condi-
*Molecular Pharmaceutics: Pb-azie, in press.
Part 37;
Part 361
Cons, a steroid compound (1% norethisterone acetate) was distributed through different samples of lactose, which had previously been adjusted to different degrees of order by employing impact milling [7] and subsequent fractionating sieving (the fraction with 0.16 0.25 mm particle size was used). Eiectrostatic charges and agglomerates were removed by addition of 10% talc. For the mixing process a falling mixer was used. After 40 min, 10 samples were taken from different positions of the powder bed. They were extracted with methanol and evaluated spectrophotometritally at 240 nm. On the basis of ten values each the relative standard deviation was calculated. The results for homogeneity and content uniformity, respectively, are given in Fig. 1.
0
70
20
30
I ,
I 0.9
I 0.8
I 0.7
p-r&-J]$zpg degree Of order
Fig. 1. Plot of relative standard deviation us. milling time and degree of order.
It is evident from the shape of the curve that a direct relation exists between the degree of disorder and the degree of homogenization. The correlation is linear. Increasing disorder of the chief ingredient corresponds to a better ability of blending and results in a better homogeneity. In order to obtain highquality mixtures a mechanical pretreatment of the solids is advisable; for example, by introducing a trituration.
290 REFERENCES 1 L. Ehrhardt, Mischen in fester Phase, APV-Informatiansdienst, 17 (1971) I- 20. 2 H. Egermann, Der Einfluss von Pulvereigenschaften auf das Fliessverhaiten und d-n Bedeutung in der pharmazeutischen Technologie, APV-Informationsdienst. 19 (1973) 134 - 146; 20 (1974) 8 - 38, 117 - 159. 3 H. Egermann, Zur Anwendbarkeit statist&her Beziehungen fiir die Berechnung der bestmijglichen Gehaitseinheitlichkeit in niedrigdosierten, festen Arzneiformen, Acta Pharm. Technoi., 22 (1976) 131 - 141,207 - 215_
4 H. Sucker, Magiichkeiten zur Verb esserung der Dosierungsgenauigkeit, Acta Pharm. Technol., 23 (1977) 153 - 171. 5 K. Sommer, Mechanismen des Pulvennischens, Chem. Ing. Tech., 49 (1977) 305 - 311. 6 R. Hiittenrauch, Bedeutung der GitterstSrungen an FeststoffoberflZchen fiir den Verlauf von Mischvorggngen, insbesondere fiir die Einarbeitung und Wirksamkeit von GIeitmittein, Pharmazie, 32 (1977) 802 - 803. 7 R. Hiittenrauch and Ingeburg Keiner, Mechanochemische Anderung des Ordnungsgrades der Lactose bei Mahiprozessen, Pharmazie, 31 (1976) 329 - 330.
Technology.
@ Elsevier Sequoia
Short
22 (1979) 289 - 290 S.A., Lausanne -Printed
289 in the Netherlands
Communication
Influence of Lattice Defects Processes*
R. HtiTENRAUCH
upon Mixing
and I. KEINER
VEB Jenapharm. Research Department, Otto-SchottStrasse 13, 69 Jena (German Democratic Republic)
(Received
October
17,197s)
Mixing of solids represents the most important unit operation in powder technology. According to the results obtained so far, the process is influenced by the folldwing material factors [1 - 51 : particle size, particle size distribution, particle shape, particle density, bulk density, surface roughness, agglomeration tendency (adhesiveness, cohesiveness), flow behaviour and electrostatic charge. Besides this we observed recently, through indirect evidence, that the mixing rate depends upon the degree of order at the solid surface [S] . As is well known, the strength of compacts varies with the incorporation time and with the homogeneity of lubricants in the material. We found that this time effect is determined by the degree of order in the bases. Mechanically activated and imperfect. solids result in a more rapid and more homogeneous distribution of the lowclosed component than non-activated ones. Therefore, lattice defects as active points probably regulate aU interactions at the surface of a solid. Like other phenomena, the interparticular adhesion depends on the degree of order- A more extensive and more intensive adherence may decrease the extent of individual segregation steps and, thereby, increase the ability to homogenize. Lattice defects may function in the same way as low humidity. To confirm the important influence of lattice_ defects, a direct demonstration was undertaken. Using constant mixing condi-
*Molecular Pharmaceutics: Pb-azie, in press.
Part 37;
Part 361
Cons, a steroid compound (1% norethisterone acetate) was distributed through different samples of lactose, which had previously been adjusted to different degrees of order by employing impact milling [7] and subsequent fractionating sieving (the fraction with 0.16 0.25 mm particle size was used). Eiectrostatic charges and agglomerates were removed by addition of 10% talc. For the mixing process a falling mixer was used. After 40 min, 10 samples were taken from different positions of the powder bed. They were extracted with methanol and evaluated spectrophotometritally at 240 nm. On the basis of ten values each the relative standard deviation was calculated. The results for homogeneity and content uniformity, respectively, are given in Fig. 1.
0
70
20
30
I ,
I 0.9
I 0.8
I 0.7
p-r&-J]$zpg degree Of order
Fig. 1. Plot of relative standard deviation us. milling time and degree of order.
It is evident from the shape of the curve that a direct relation exists between the degree of disorder and the degree of homogenization. The correlation is linear. Increasing disorder of the chief ingredient corresponds to a better ability of blending and results in a better homogeneity. In order to obtain highquality mixtures a mechanical pretreatment of the solids is advisable; for example, by introducing a trituration.
290 REFERENCES 1 L. Ehrhardt, Mischen in fester Phase, APV-Informatiansdienst, 17 (1971) I- 20. 2 H. Egermann, Der Einfluss von Pulvereigenschaften auf das Fliessverhaiten und d-n Bedeutung in der pharmazeutischen Technologie, APV-Informationsdienst. 19 (1973) 134 - 146; 20 (1974) 8 - 38, 117 - 159. 3 H. Egermann, Zur Anwendbarkeit statist&her Beziehungen fiir die Berechnung der bestmijglichen Gehaitseinheitlichkeit in niedrigdosierten, festen Arzneiformen, Acta Pharm. Technoi., 22 (1976) 131 - 141,207 - 215_
4 H. Sucker, Magiichkeiten zur Verb esserung der Dosierungsgenauigkeit, Acta Pharm. Technol., 23 (1977) 153 - 171. 5 K. Sommer, Mechanismen des Pulvennischens, Chem. Ing. Tech., 49 (1977) 305 - 311. 6 R. Hiittenrauch, Bedeutung der GitterstSrungen an FeststoffoberflZchen fiir den Verlauf von Mischvorggngen, insbesondere fiir die Einarbeitung und Wirksamkeit von GIeitmittein, Pharmazie, 32 (1977) 802 - 803. 7 R. Hiittenrauch and Ingeburg Keiner, Mechanochemische Anderung des Ordnungsgrades der Lactose bei Mahiprozessen, Pharmazie, 31 (1976) 329 - 330.