dx.doi.org/10.14227/DT020395P5
A Brief Overview
on Dissolution Testing
of Vitamins, Minerals, and
Nutritional Supplements
'
A:
open co nfere nce on Vitamins, Minerals, and
N utritional Supplements was spollsored by
the United States Pharmacopeial Convention (USP) in Scottsdale, Arizon" in JWle
199 1[1 ]. The purpose of this co nfe re nce w"s to
explore the possibility of outlining standards for
quality and performance of nutri tiona l supplements.
There is a wide va ri ation between the type of
stand ards necessary for drugs and the type of stand;uds necessary for nu t riti o nal sup plements. For
example, there is a strong dose/response relationship in drugs tha t is non-existent with nutritional
ingredients. Evidence has eve n been su bmitted
where, in so me cases, tht.:rc is an inverse relationsh ip between disso luti on time and
USP DISINTEGRATION APPARATUS
biologica l ava ilability with some
forms of nutri tional supplements.
STROKE. 3D/MIN .
'rhercforc, the
em
following new test
1000-mL BEAKER
concepts
were
in troduced at t his
J- 6 GLASS TUBES. 1in. Die .
conference. O n the
J- rlPLASTIC DISKS
Cl Cl
8
.8
l - I- TABLET
assumption that little or no absorp10-MESH SCREEN
tion would take
place w ith o ut <1
breakdown of the
STANDARD
-SIX TUBES (APPARATUS A) WITH DISCS
so lid dosage form,
- THREE TUBES (APPARATUS B) WITH DISCS
-10-MESH SCREEN
an initial test using
USP
DisintegMODIFICATIONS
ration Apparat us
- MEDIA AND TIME
"A" (figure 1) was
USEFUL FOR
required.
The
- NUTRITIONAL SUPPLEMENTS
a ppa ra tus
was
Figure J: SdJellllllic l)illgrll111 of u SP DisilllegmtiQII
expa nd ed into a
ApPllrtltlfSA & 11.
larger size, ApparaU IS "B" (figure I), to accommodate tab lets greater
th,-ln or equal to 18 mm long. For d isso lu tio n
analysis, the concept of an index component was
introduced. The index compo nent refers to one
vitami n or mineral of a multiple vitami n or nliner-
r-6
Marvin Delgado, Royal Hanson,
and William Hanson, Ph.D.
l-/aJJson Resellrch C01p., Chfltsworth, CA
al formul atio n that is selected for assay to determine the dissolution time.
March 1993
Standards established in Supplement 8 to USP
XXIJ I NF XVI] [2] required initial disintegration
testing on nutritional supplemen ts. If the product
fajled to meet t he disintegration criteria, dissolution testing wo uld be required o n the product.
The disintegration test was performed using USP
Disintegration Ap pa ra tus A for dosage forms
under 18mm and Appa ratlls B for dosage forms
greate r than or equa l to 18 mill long. Refer to
Table I for the disintegration testing req uirements established for eac h type of dosage form.
Table 1
Disintegration Requirements for
Nutritional Supplement Dosage
forms
• IIBI fl.M
DIII.nlllanl•
Milia
lIITI.1l nMI
Uncoated and
Film·coated tablets
water
30 minutes
Coated tablets
water
1; minutes·
Hard or Soft
Gelatin Capsules
0.05MAcetalC Buffer
45 minutes
'Soak in water for j
minut~ prior to testing
-
"
Six samples are tested ini tially. At the end of the
specified testing time, the appararus is exa mined
fo r the presence of any palpable mass indicating
incomplete disintegration. If o ne or two of the initial six dosage forms fai l to disintegrate completely, twelve more samples are tested. Of the 18 samples, at least 16 samp le s Illllst disintegrate
completely. If the sample fai ls to meet these disintegration criteria} dissolutio n testing is
perfonlled on six additiona l samples.
The dissolution testing of nutritional
sup pleme nts is performed in 0.1 N Hel
Disso/lllioIlTecbll%giesIAUGUST 1995
Dissolution Testing ... continued
media. USP Dissolution Apparatus I (rotati ng
basket) at 100 RPM is specified for testing capsules. USP Dissolution Apparatus 2 (paddle) at 75
RPM is specified for testing tablets. Compliance
to the dissolution specific~1tjons estab lished for
nutritional supplements is determined by measuring t he dissolution of o ne component selected as
the index vitam in o r mineral. T he following criteria were o utlin ed in S uppl ement 8 to USP
XXTI/NF xvn[21 for the selection of the index
component.
Index Vitamins and Minerals
From the list below, choose the first
vitamin/mineral present in the
dosage form.
Water-solu bleV i rami ns
Capsulesrrablets,
Oi l- andWater-solu ble
Capsulesrrablets
I.
2.
3.
4.
Pyridoxi ne
N iaci n
Thiamin
Riboflavin
,Wneral
I.
2.
3.
4.
[ron
Calcium
Zinc
Magnesiulll
Capsulesfrablets
January 1995
C hanges to the Nutritional Supplement disintegratio n and dissolution testing requirements
were proposed in Phannacopeial Forum, 19(6)[3].
These proposed modifications to the testi ng criteria for nutritional supplements were adopted by
rh e USP and beca me effective on Janu ary 1, 1995,
as stated in Supplement I to USP 23 I NF [8[4].
T he new disintegration and dissolution criteria for
nutritional supplements require that the preljminary disintegration requirement for water soluble
vitami ns and minerals be replaced with the dissolution test. A new classification of nutritional supplements and the ir dissolution testing requirements was o utlin ed in Supplement 1. to USP 23/
NF 1814/ (Table 2).
Table 2
Classification of Nutritional
Supplements
Inert"I•• II Nllrltll••1
.1'
CIIII ••"1••••'
11
fJJ
Select one
index vitamin
and minera l
from the
above lists
nor applicahle
one index vitmnin
one index \"itamin
and one index
clement
IV
Water-soluble Vitamins
with Minerals,
Capsulesrrablets
Oil-soluble \ 'iramins
Waler-soluble \ 'it<lmins
\V:Hcr-soluble Vitamins with
Alinernls
IIIHIIII••
l lIt.lre•••'
v
Oil- and Water-soluble Vitamins One index water
soluble \-immin
Oil- and Water-soluble
One index watcrVitamins with Minerals
soluble vitamin and
one index element
,\iincrnls
one index element
In addition, the fo llowing modification in the
selection order of dle index components was also
incorporated.
At the one hour time point, aliquots are withdrawn from each of the six samples. T he aliquots
are combined and assayed for an average va lue of
the index component from dlC six samples. T he
dissolution requirement is met if not less tha n
75% of the labeled content of rhe assayed index
component is dissolved in one hour.
continucd next page
Di.l:fo/mioIlTecim%giesIAUG UST 1995
Index Vitamins and Minerals
From the list below, choose the first
vitamin/minerai present in the
dosage form.
Water-soluble vitamins
Mi ne rals
I.
2.
3.
4.
5.
Riboflavin
Pyridoxine
N iaci n
Thiamine
Ascorbic
Acid
I. [ron
2. Calciulll
3. Zinc
4. Magnesium
According to Supplement 2 to USP 23 / NF 18[5],
a dissolution test for folic acid is required when the
nutritional supplements' labeling includes ::1 hea lth
claim concerning fobte deficiency and the risk of
neural nlbc defects.
Overa ll , the dissolution requirements for nutritional supplements have increased dramaticJlly with
the recent changes in the USP Nutritio nal Supple.
ment testing criteria. As this area of dissolution testing continues to evo lve, the current USP supplements shoul d be carefu ll y reviewed to ascertain that
the appropriate nutritiona l supplement testing criteria 3rc being used.
References:
I.USP Open Conference 0 11 Vitamjns, Minerals, and
Nutritional Supplements, Scottsdale, Arizona, june
199 1. Proceedings avai lable from USP, 1260 1 Twinbrook Parkway, Rockville, MD 20852.
2. USP XXIV l'-'F )"'VII, Supplement 8, Pl'. 33683369, March 1993
3. Pharmacopeia I Forum,19(6), PI'. 6605-6607, NovDec 1993
of. USP 23 / NF 18, Supplement I, Pl'. 2577-2578,
Nov 1994
5. USP 23 / NF 18, Supplement 2, PI'. 2833·2834,
March 1995
Disso/lltiouTecim%gies/ AUGUST 1995