EFFECT OF SOLID DISPERSIONS WITH POLYETHYLENE
GLYCOL 1500 ON THE SOLUBILITY OF INDOMETHACIN
I. I. Krasnyuk, Jr.,
T. M. Kosheleva,
A. V. Belyatskaya,
I. I. Krasnyuk,
O. I. Stepanova,
V. V. Grikh,
and L. V. Ovsyannikova
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 52, No. 3, pp. 46 – 49, March, 2018.
Original article submitted July 10, 2017.
Solid dispersions (SDs) of indomethacin with polyethylene glycol 1500 (PEG-1500) were studied to deter
mine their effect on indomethacin solubility. Production of SDs increased the solubility and dissolution rate of
indomethacin in H
O. The solubility and dissolution rate of indomethacin from SDs increased by 1.8 – 2.2 and
3.1 – 4.4 times, respectively. Indomethacin became less crystalline and then amorphous during preparation of
the SDs. Dissolution of the SDs solubilized indomethacin and formed colloidal solutions.
Keywords: indomethacin, solid dispersions, polyethylene glycol 1500, solubility, crystallinity.
Indomethacin is one of the most potent nonsteroidal
anti-inflammatory drugs (NSAIDs) [1, 2].
One of the difficulties with developing indomethacin
drugs is its low water solubility (0.937 mg/L at 25°C) .
Experimental results indicated that NSAIDs were more effi-
cacious if added to dosage forms (DFs) as solid dispersions
SDs are bi- or multicomponent formulations of an active
ingredient (AI) and carrier and are represented as a highly
disperse solid AI or a molecularly disperse solid solution
with partial formation of various complexes with the carrier.
Various polymers could be used as the carrier [4 – 11].
The goal of the work was to study the effect of preparing
a SD on indomethacin dissolution.
Indomethacin drug substance (Sewei Development
Group Ltd., China) meeting regulatory requirements was stu
died in the work. The polymers were PEG-1500 (Merck,
SD preparation technology was based on the physico-
chemical properties of the components. The optimal mass ra-
tio indomethacin:polyethylene-glycol-1500 (PEG) was 1:5
according to the research results and the literature [4 – 10].
SDs with PEG were prepared by removing solvent. The com-
mon solvent was EtOH (95%). The calculated amounts of AI
and polymer were dissolved in EtOH. The solvent was evap-
orated to constant mass in vacuo with vigorous stirring in a
water bath at 75 ± 2°C. A mixture of indomethacin and PEG
was prepared by grinding together AI and polymer (1:5 mass
ratio) in a pharmacy mortar.
The developed modified procedure was used to study the
solubilities and dissolution rates of AI and SDs using a mag
netic stirrer (RCT Basic, IKA, Germany) with heating con
trolled by a thermostat.
UV spectrophotometric studies used a Unico Model 2800
UV spectrophotometer (Single-Beam Scanning UV/Visible
Spectrophotometer) and 10-mm quartz cuvettes. The ob
tained SDs with PEG were viscous, sticky, transparent, yel
low masses. The mixture of indomethacin and PEG was a
white powder with a yellow tint.
The basic experimental problem was the inability to use
the Dissolution test according to GPM 1.4.2.0014.15 because
saturated solutions were produced. The obtained SDs could
be powders or viscous sticky masses of soft or waxy consis
tency. The conditions described in GPM 1.4.2.0014.15 (SP
XIIIth Ed.) were not always suitable so new ones had to be
elaborated. Studies of dissolution rates according to the GPM
Pharmaceutical Chemistry Journal, Vol. 52, No. 3, June, 2018 (Russian Original Vol. 52, No. 3, March, 2018)
0091-150X/18/5203-0241 © 2018 Springer Science+Business Media, LLC
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