The document summarizes two journal articles about using mixed solvency and hydrotropic solubilization techniques to improve the solubility of poorly soluble drugs rifampicin and aceclofenac. The first article formulates an oily injection of rifampicin using solubilizers like PEG and benzyl alcohol. The second article formulates an aqueous injection of aceclofenac using hydrotropic blends of urea and sodium citrate. Both studies evaluated the solubility enhancement, stability of formulations, and effect of environmental factors on drug degradation. The conclusions were that mixed solvency and hydrotropy techniques increased drug solubility and stable formulations were successfully developed for rifampicin and aceclofen

1. #Journal club#
submitted by
Mr.Santu S.Mistree
( B.Pharm )
Research guide
Proff.Dr.M.D.Kshirsagar
(M.Phrma,PhD)
Department of pharmaceutics,
p. wadhwani college of pharmacy , Yavatmal
(445001)

2. TITLE
 Formulation , development
and evaluation of poorly
soluble drug using mixed
solvency concept
RESEARCHER
 R. K. Maheshwari
 Rajendra Shilpkar
SOURCE
 International Journal of
Pharma and Bio Sciences
 Formulation , development and
evaluation of poorly soluble
drug by using hydrotropic
solubilization technique
RESEARCHER
 R.K. Maheshwari
 Arpna Indurkhya
SOURCE
 Iranian Journal of
Pharmaceutical Research

3. INTRODUCTION
 Mixed solvency is the
phenomenon to increase the
solubility of poorly soluble drug
by using blends of co-solvents.
 E.g: PEG , Benzyl alcohol
 Model drug is Rifampicin
 Mixed solvency is a technique
, proposed by Maheshwari .
 According to his opinion, that
all substance, either liquid ,
gases or solids possess
solubilizing power and hence ,
co-solvents can improve the
solubility of poorly water
soluble drug .
 Mixed hydrotropic is the term
used to enhance the solubility
of poorly water soluble drug by
employing blend of hydrotropic
agents.
 E.g : Sodium citrate, Urea
 Model drug is Aceclofenac
 Hydrotropic is the term put
forward by Neuberg .
 He said that by addition of
fairly high concentration of
alkali metal of various organic
acids is possible to increases
the solubility of solute.

4.  The objective of present
research is to explore the
application of mixed solvency
technique in the injection
formulation of poorly water
soluble drug and to reduce
concentration of individual
solubilizer to minimize the
toxic effects of solubilizers.
 In the present work, rifampicin,
a poorly oil soluble drug
selected as a model drug and
attempts were made to
formulate an oily injection of
this drug using various model
solubilising agents.
 The objective of the present
study is to explore the
application of mixed hydrotropic
solubilization technique in the
formulation of dosage forms of
water- insoluble/poorly water
soluble drugs and to reduce the
concentration of individual
hydrotropic agents to minimize
their side effects.
 In the present work, aceclofenac
is non-steroidal anti-
inflammatory agent selected as
a model drug which is a BCS
class II drug (highly permeable
and low soluble) and attempts
were made to formulate an
aqueous injection of this drug,
using various hydrotropic
agents.

5. MATERIALS
 The gift sample of rifampicin
provided by Torrent
Pharmaceutical Limited,
Ahmedabad, India. Thymol,
camphor, menthol
purchased from local
market. Ethyl oleate oleic
acid and phenol (Merck,
Ltd., Mumbai, India) were
also used. All other
chemicals and solvents
used were of analytical
grade.
 The gift sample of aceclofenac
provided by IPCA Laboratories
Ltd. Ratlam, India. Urea
(Merck, Ltd., Mumbai, India)
and tri-sodium citrate dihydrate
(Loba chemie, Mumbai, India)
were also used. All other
chemicals and solvents used
were of analytical/HPLC grade.
Membrane filter (0.22 μm),
(Sartorious, Germany),
aluminium seal, glass vials (15
mL), and rubber plugs (Modern
Labs, Indore, India) were also
employed in this study.

6. EXPERIMENTAL WORK
 Solubility study .
 Formulation of injection
dosage form.
 Accelerated stability study.
 Effect of sun light on drug
degradation.
 Effect of atmospheric oxygen
on stability.
 Selection of hydrotropic
blends.
 Determination of equilibrium
solubility.
 UV spectral studies.
 Thin layer chromatographic
studies.
 Formulation of the aqueous
lyophilized injection :
 Preparation of an aqueous
solution of aceclofenac.
 Treatment of packaging
material.
 Preparation of an aseptic area.

7.  Aseptic filtration.
 Final flushing with the nitrogen
gas.
 Freezing process.
 Drying process.
 Characterization of the
formulated lyophilized
aceclofenac injection :
 Moisture uptake kinetics.
 XRD studies on the
formulated lyophilized injection
.
 Study of reconstitution time.
 Clarity testing of reconstituted
injection.

8.  Stability studies :
 Stability of aceclofenac in bulk
solution.
 Physical stability study of
formulated lyophilized injection
of aceclofenac.
 Chemical stability study.
 Dilution profile of the
reconstituted injection.

9. RESULT
 Solubility studies :
 The observed solubility of
rifampicin , shows the
synergistic enhancement in
the solubility.
 Accelerated stability
studies:
 The developed oily injection
formulations of rifampicin
showed good stability.
 The prepared formulation
showed the maximum shelf life
of 262 days.
 The solubility determination of
aceclofenac was carried out in
distilled water, hydrotropic
solutions (30% urea and 30%
sodium citrate) and solutions
containing different
concentrations of hydrotropic
agents (urea and sodium
citrate).
 Solubility of aceclofenac
increased more than 250 times
in hydrotropic blends , 5 time in
30% sodium citrate and 25
time in 30% urea .

10.  Formulations were also found
to be stable physically in
respect of color, precipitation
and turbidity.
 Effect of sunlight on drug
degradation:
 The vials which were wrapped
in aluminium foil and placed in
dark showed less degradation
of rifampicin as compared to
those which exposed to direct
sunlight.
 For maximum stability of
formulation, it should be stored
in dark place and in amber
colored vials.
 The solubility of aceclofenac
increases slightly, with an
increase in pH, which may be
due to the acidic nature of
aceclofenac.
 The results of TLC study
revealed that there is nearly no
considerable change in Rf
value of aceclofenac
solubilized in methanol and
aceclofenac solubilized in the
hydrotropic blend solution.
 The sample when kept under
controlled conditions, is safe
and there is no moisture
uptake.

11.  Effect of atmospheric
oxygen on stability:
 From the study of formulation ,
it observed that the both sets
of vials i.e. flushed with
nitrogen and not flushed with
nitrogen contained almost
same amount of residual drug
.
 From the literature it knew
that thymol had some
antioxidant properties so there
was almost no effect of oxygen
on formulation containing
thymol.
 The results of stability studies
on aceclofenac in the bulk
solution indicated that the
aceclofenac is stable in the
bulk solution for 4 h at room
temperature and 12 h under
refrigerated conditions.
 The results of chemical study
showed that the developed
formulation is sufficiently stable
at room temperature


12. CONCLUSION
 The results of solubility studies
revealed that there was
appreciable enhancement in
solubility of poorly soluble drug
rifampicin when the oil
soluble/miscible additives
added.
 The results of stability study
supported that the
formulations developed by
novel application of mixed
solvency concepts had
desirable stability also.
 It is concluded that the
solubility of aceclofenac was
increases synergistically by
mixed hydrotropy.
 In conclusion, the findings of
this study suggest that a stable
lyophilized aqueous injection
of aceclofenac has been
successfully developed.
 The proposed techniques
would be economical,
convenient and safe.

13. REFERENCES
 Neuberg C. Hydrotropy.
Biochem. Z. (1961) 76: 107-
109. Maheshwari RK. Analysis
of frusemide by application of
hydrotropic solublization
phenomenon.
 Indian Pharmacist (2005) 55-8.
Maheshwari RK. New
application of hydrotropic
solublization in the
spectrophotometric estimation
of ketoprofen in tablet dosage
form. Pharma Review (2005)
123-5.
 Maheshwari RK, Solubilization
of Ibuprofen by Mixed
Solvency Approach. The Indian
Pharmacist, 8 (87): 81-84,
(2009). 2. Maheshwari RK,
Mixed-solvency approach –A
Boon for Solubilization of
Poorly Water Soluble Drugs.
Asian Journal of
Pharmaceutics, January-
March, 60-63, (2010).
 Maheshwari RK, A Novel
Concept for Solubilization of
Poorly Water Soluble Drugs.
Journal of Technology and
Engineering Sciences, 1,
January-June, 39-44, (2009).

14. THANK YOU