Group B2 - Assignment 1

Properties for Processing. Riboflavin (vitamin B2) is isolated by filtration and polishing
by spray drying. The efficiency of both processes (higher yield per unit time) increases
with increasing temperature. Find the necessary handbook data and determine the
maximum temperature at which u could run these two unit operation.

Vitamin B2 or riboflavin importance in functioning metabolic system concerned with

the oxidation of carbohydrates and amino acids. It is not in the free form but in more
complex compound known as coenzymes, such as mononucleotide (FMN) and flavin
adenine dinucleotide (FAD), or flavoprotein. It plays an important role in energy metabolism
of fats, ketone bodies, carbohydrates and proteins.

Figure 1: Chemical Structure of Vitamin B2 (Takayuki et al., 1999).

The process for the purification of riboflavin (vitamin B 2) is particularly suitable for
the removal of DNA associated with riboflavin crystals. Riboflavin is produced by

microorganisms and the pure product is obtained by consecutive purification steps starting
from the crude reaction slurry (fermentation broth) containing the riboflavin. The process for
the purification of riboflavin comprising the steps below:
(a) Precipitating a first crystalline form of riboflavin,
(b) Isolating the first crystalline form of riboflavin,
(c) Transforming the first crystalline form of riboflavin into a second crystalline form of
riboflavin under conditions that decompose diluted DNA, and
(d) Isolating the second crystalline form of riboflavin, provided that at ambient temperature
(which is average room temperature, preferably 23C) the first crystalline form of
riboflavin is thermodynamically less stable than the second crystalline form of riboflavin.

Depending on the temperature the following crystalline forms are in equilibrium with
one another or are irreversibly transformed into each other under defined conditions:
riboflavin anhydrate I with riboflavin dihydrate and riboflavin tetrahydrate; riboflavin
anhydrate II with riboflavin monohydrate and riboflavin dihydrate; riboflavin anhydrate III
with riboflavin tetrahydrate.
At 23C, riboflavin anhydrate I and riboflavin dihydrate can be illustrated as follows:

At 23C, the equilibrium between riboflavin anhydrate I and riboflavin dihydrate is

completely shifted to the side of riboflavin anhydrate I. At this temperature riboflavin
dihydrate is irreversibly transformed into riboflavin anhydrate I. Thus, at 23C no riboflavin

dihydrate can be obtained from pure riboflavin anhydrate I. At higher temperatures 39C,
riboflavin dihydrate is thermodynamically less stable than riboflavin anhydrate I.
At 23C, the kinetic of the transformation of riboflavin dihydrate into riboflavin
anhydrate I is slow. Stirring a slurry containing pure riboflavin dihydrate at a temperature of
23C results in a partial transformation (80%) into riboflavin anhydrate I in 2 days
(determined by Raman spectroscopy). At 39C, the differences of the solubility or the
chemical potentials are small. Therefore, at this temperature the transformation of riboflavin
dihydrate to riboflavin anhydrate I is slow.
At higher temperatures, the difference between the chemical potentials of riboflavin
anhydrate I and riboflavin dihydrate increases. Therefore, the velocity of the transformation
process significantly increases, as riboflavin dihydrate is completely transformed into
riboflavin anhydrate I within 20 seconds at 80C.
However, at 4C the thermodynamic situation is different. In an aqueous slurry
riboflavin anhydrate I can be transformed into riboflavin dihydrate, the latter being
irreversibly obtainable from riboflavin tetrahydrate (particularly at higher temperatures):

At 4C, the kinetic of the transformation of riboflavin anhydrate I into riboflavin

dihydrate is very slow. Stirring a slurry only containing riboflavin anhydrate I at a
temperature of 4 C leads to a partial transformation (80%) of riboflavin anhydrate I into
riboflavin dihydrate in 56 days.

Riboflavin: Decomposes at 278-282C (darkens at about 240C)

A method for producing a granulated riboflavin product comprises making a specific

mixture of riboflavin, binder and water, followed by homogenizing the mixture and
thereafter spray-drying the homogenized mixture so that granules are produced.
Using a laboratory size spray-drying apparatus, the previously prepared
homogenized riboflavin suspension was metered to the atomizing wheel. The atomizing
wheel (a slotted wheel obtained from Niro Atomizers, Inc., 9165 Rumsey Road, Columbia,
Md., as used in utility dryer Model IV) was operated at 21,000 rpms, a centrifugal speed of
about 8,000 meters per minute. The inlet air temperature flowing into the spray dryer
chamber was about 200 C., and the outlet air temperature was about 100 C. The riboflavin
suspension was fed into the spray atomizing wheel at a rate of about 125 grams per minute.
The resulting riboflavin powder was an orange, free-flowing, static-free powder having
a bulk density of 0.43 grams per cubic centimeter with a geometric mean particle size of
about 58 microns and a log standard deviation of about 1.5 microns. Furthermore, the

powder had a flowability index (as measured by the Flodex method) of at least 333. [A
flowability index greater than 100 is indicative of excellent flowability.] This powder mixed
well in flour premixes and produced directly compressible tablets with the hardness of 12
scu. The final product was made up of about 94 weight percent riboflavin, 5 weight percent
binder, and 1 weight percent water.
In conclusion, the optimum temperature to spray-dry the riboflavin is 200 ,
which lead to the production of 94 weight% of granulated riboflavin. From Merck Index,
riboflavin decompose at the range from 278

to 282 , and darken at 240 .

This mean that, the maximum temperature to crystalize riboflavin is in the range between
230 and 239 .

Reference:
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and
Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1413

Process for spray drying riboflavin to produce a granulate product having low binder
content (n.d.). Retrieved on 8 March, 2015 from
https://www.google.com/patents/US5000888