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Abstract: In the present study an attempt
has been made to increase the dissolution rate of poorly
water soluble drug itraconazole, by employing novel
cogrinding method using four carriers, namely, lactose,
cornstarch, pregelatinized starch and sodium starch
glycolate. The coground mixtures were prepared in three
different drug-carrier (w/w) ratios of 1:1, 1:3 and 1:5.
The mixtures were evaluated for drug content uniformity,
drug-carrier interaction ( FTIR) and dissolution
characteristics. The formulation with drug-carrier ratio
of 1:5 (itraconazole-pregelatinized starch) showed
promising results with t70% value of 8 min compared to
pure drug (t70%>90min). Capsules prepared from this
mixture displayed six-fold increase in the dissolution
efficiency compared to commercial capsule formulation of
itraconazole (DE30min values of 66.86% and 10.60%
respectively). Short term stability studies (at 40oC /
75% RH for 3 weeks) of the designed capsule formulation
showed no significant changes in the drug content and
t70% value (p<0.05). This study proves that cogrinding
technique can be used for enhancing the in vitro
dissolution characteristics of the poorly soluble drug
itraconazole.
Introduction: The poor dissolution
characteristics of relatively insoluble drugs have been
a problem to the pharmaceutical industry. When an
insoluble or sparingly soluble drug is administered
orally, the rate and extent of absorption are controlled
by the dissolution rate in the gastrointestinal fluids.
Itraconazole (ITR) is a triazole antifungal and has a
broad spectrum of activity. It is used to treat fungal
infections in immunocompromised and non-immunocompromised
patients who have cryptococcosis, blastomycosis, and
aspergillosis. It is practically insoluble in water and
its absorption is dissolution rate limited.1 Therefore,
in the present study an attempt has been made to
increase its dissolution rate by novel co-grinding
method. Though the solid dispersion technique is an
attractive method in the dissolution enhancement of
poorly water-soluble drugs, many challenges have limited
its application in the design of the dosage forms.2 Some
of the limitations are difficulty in pulverization and
sifting of the dispersions, which are usually soft and
tacky,3,4 poor flow and mixing properties, poor
compressibility, drug-carrier incompatibility and poor
stability5 of the dosage forms. Ordered mixing,6 roll
mixing,7 complexation,8 cogrinding,9 cogrinding in
presence of small amount of water10 are some of the
alternative reported methods for enhancing the
dissolution rate of poorly water-soluble drugs with an
aim to the development of suitable formulation for oral
use. Enhanced dissolution rate of ITR by the formulation
of inclusion complexes with α, β, γ and hydroxypropyl β-cyclodextrins
was reported11. In the present work, studies were
carried out on the role of cogrinding in enhancing the
in vitro dissolution characteristics of itraconazole
using various excipients, namely, lactose (L), corn
starch (CS), pregelatinized starch (PGS) and sodium
starch glycolate (SSG) with a view to improve the
dissolution rate and develop fast release formulations
fulfilling the official dissolution requirements, thus
enhancing the bioavailability of the drug.
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