From the Research Laboratories

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SOLUBILITY AND DISSOLUTION

ENRANCEMENT OF IBUPROFEN
BY SOLID DISPERSION
TECHNIQUE USING PEG 6000-PVP
K 30 COMBINATION CARRIER

M. Saquib Basnain, Amit Kumar Nayak

Seemanta Institute ofPharmaceutical Sciences, DIDIA

Abstract Ibuprofen solid dispersions were prepared with the objective of

solu- bility and dissolution improvement using PEG 6000-PVP K 30 combination
carrier by solvent evaporation technique. The saturation solubility and in vifro
dissolution studies showed remarkable improvement in solubility and drug dissolution
of these new ibupro- fen solid dispersions over pure ibuprofen, ibuprofen solid
dispersions using PEG 6600 and PW K 30, individually and physical mixtures. The in
vine drug dissolution from these new ibuprofen solid dispersions was followed
Hixson-Crowell model. The XRD and DSC studies indicated the transformation of
crystalline ibuprofen (in pure drug) to amorphous ibupmfcn (in solid dispersions
using PEG 6000-PVP K 30 combination) by the solid dispersion technology. Stability
studies of these solid dispersions does not show any significant changes (p < 0.05) in
dnig content and drug dissolved in 60 minutes (Qm i«. %) within 6 months study
periods (at 25 4 2°C and 60 -£ 5 % RH). This study concluded that the improvcd
solubility as well as drug dissolution of these new ibuprofen solid dispcrsions using
PEG 6000-PVP K 30 combination may be attributcd to improved wettability, and
reduction in dnig crystallinity, which can be modulated by appropriate level of
hydrophilic carriers.
K eywonis: solid dispersion, ibuprofen, solubility, dissolution, polyethylene glycol,
polyvinyl pyrrolidone
J18
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European Journal of Pharmaceutical Sciences

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Solubility and dissolution rate enhancement of ibuprofen by co-milling with

polymeric excipients m
Amjad Hussain *", Geoff Smith"’ ‘, Karrar A. Khan'", Nadeem Irfan Bukhari", Nicholas I. Pedge'',
tina Ermolina*'

be aim of this study was to cnhnce jJje kjneric soJubilJty and tssolutioo rate of ibuprnFen by co-milling
with diPernt copieors and in nca6)icfi the wdolyng mecfi (s) for such cr+Panel. Fn the first-part. two
alpiene (PfPMc and soluplus3 owe selected from men, and the optimal ball-mming paremetws of speed
and
tame (ie in i s min3 were determine en selub inyci ancem ent nd fiow-abiliy ccrit er i« ‹he u»d-
part. en-r#1tti% of diff t ••eignt-rafios of ibuprofen-i 0pie»t we canniest out and selubilly arid
dismIuct‹•» raw wa• determined. txt ecnariism of bJopnarin aceucic•I e nancemoi ••ew studied @ 8E , lv
diffrac ion. and F•fT1t analyze or the ceni•turo. ibupref'en colubJlity tO.09
m@mL for nut hcd ) was mereased by
s ra«»‹• +-s ma io-zo r« unuc md wi»9in « ••iy. rr'• wni• •e « ‹=r••«, s •siiu•ti•• •f ‹#•
amorpljone plc e and an Iners In selid•tate hydiegen bondirug are me Rely mech an Jm for MM
en- h•ncextent. deductions In Q7o% dissolution dme www also obser•cd, by a feeder of 4 and 2 for ibuprofenl
IMPS and tbuprofen•m1up1u• co-mi fled miwures, opectively. Aft oegh, ifiwr were firnilar redvehoru in
parbcte Hze. 6t persibilly and Spec of wnorphimdon in both ‹matures, be hirer dJssolufleri rate for Wuplus.
over that for rlPMC. n net br due to the addJfionat solubiltznoon conn-thud on to ifie kineñ c soTubiliry

goaded by soJuplus

solid srate and il i) reduce the mechanical Zthermal degradation of drugs

Billing and co-mi ing (wfifcfi 1s defined ar mifiing io the presence
uF an ezcipient) are well known tectu+igues that have a pasiGve
in/)u- ence on the fiTnettc solubf)ity and dfiao)vdon rate of sga
tngJy soluble rugi aha is ct a., , za ranicc w a.. .
est grore u+”z haye glen shown tu provide
a érople. eMocnt aad <coooagcaJ +aethod that docs nut require any
particularly sogktsl cared equipment (Fisficr,
:2I u?). Moreover, the raethod has lv environmental impact as Ir
doee not require the use any organic sol ent (Fncd ricfi et a).. 2005).
Co• m¿tl g rgmbtrj e,s gje adyanjzg@ oF a reduction In gardcle size
and the aegrg +izacton ur a staJJTne drug substance, wkJch are the
benefit of cgnvqntlonal milling g/ single marcrlats, and have che
additional bm- cfTts oj' fmprovod wnabf}Iry and so)ubi7*¥adac that
aro provided by It+e
eo•wiilted ezcjpient (g1ooh orra 1 a nil Nv•Ir inn , 1990)• FurthWore, t
roay a$5p; j) ppw9 wit aggregati9n by tfie surHce coverage of the
charged yzxtltl es produced hy mifftngJ, 11) stabilize the amorpfleus
phs lr the
20j 0).
So)ubitity is a physicochctaica4 prog<zty oF substaace. wkich de.
g<eds on the thcrrriodyriam c proper es of the cgstal lanice ti.e. che
twcen solute-soluie and solute-solvenr (solvation) meraceioris in
the solution slate. The blute-sol vent iritemcfions may be changcd by
adding otfier cfierrkmls to the seizeug for Ma‹rtpie surface pp wfiJc5
provide a mlcellar environment for the solubllizati oq of tfie drug. lt
¿ M iai9ortnnt m ceainm6ev that the solußility of a mi£lcd erystalline
material, containing metastable (panially amorpbous) Nase, rc-
solubility tRrina in, in 14).
The rate oF disso)ucion, wbich deltas tbc rate g/ pass tr # Gom
US stAlJioe state to the dissolved (sa(ué a@ state) ¡s cgupled tg /q
sa)ubTIig but is atso impacted by acoibutos gf the oiater¡aj sjj/ as cjj#

,tbbJ¢9¢y Plfg physical mlxiu fe; mPM, milled phJcal mixture; A, e6 or6anm
•G nding audior at- Pbwmaceuticel TecbnelogjH. Rese •1i Group, Leicester Scltoél of Pharmacy. Oe Mention Uoivwsi y, The 6 atcw•y, b#¡cHet Lyj gg}I,