Download a) Brief resume of the intended work 6.1 Need of Study: The

a) Brief resume of the intended work
6.1 Need of Study:
The solubility behaviour of drug is one of the most challenging aspects in formulation development. Therefore
different approaches are being explored to enhance the solubility of poorly water soluble drugs, one of such techniques
is formulation in nanosuspensions1.
Nanosuspension is submicron colloidal dispersion of pure particles of drug which are stabilized by surfactants. It
consists of a poorly water soluble drug without any matrix material suspended in dispersion2.
The particle size distribution of the solid particles in nanosuspensions3 is usually less than one micron with an average
particle size ranging between 200-600 nm.
More than 40% of the drugs coming from high-throughput screening are poorly soluble in water. So, poorly watersoluble drugs show many problems in formulating them in conventional dosage forms. One of the critical problems
associated with poorly water soluble drugs is low bioavailability and erratic absorption. In order to overcome the
problems of low solubility and low bioavailability there are numerous formulation approaches such as micronization,
solubilization using co-solvent, use of permeation enhancers, oily solution, surfactant dispersions, salt formation and
precipitation technique2.
Nanosuspensions appear to be a unique & yet commercially viable approach to combating problems like poor
bioavailability that is associated with the delivery of hydrophobic drugs, including those that are poorly soluble in
aqueous as well as organic media4.
A nanosuspension not only solves the problem of poor solubility and bioavailability but also alters the
pharmacokinetics of drug and that improves drug safety and efficacy3.
Nanosuspensions differ from nanoparticles, which are polymeric colloidal carriers of drugs (nanospheres and
nanocapsules), and from solid-lipid nanoparticles (SLN), which are lipidic carriers of drug. In case of drugs that are
insoluble in both water and in organic media, instead of using lipid systems, nanosuspensions are used as a formulation
approach. Nanosuspension formulation approach is most suitable for the compounds with high log P value, high
melting point and high dose. The use of nanotechnology to formulate poorly water soluble drugs as nanosuspension
offers the opportunity to address nature of the deficiency associated with this class of drugs. Nanosuspension is been
reported to enhance absorption and bioavailability. It mayhelp to reduce the dose of the conventional oral dosage
forms2.
In nanosuspension technology, the drug is maintained in the required crystalline state with reduces particle
size, leading to an increased dissolution rate and therefore improved bioavailability2.
Apart from these, nanosuspensions have the following advantages:
 Drugs no longer need to be in the soluble form. It is effective for those molecules which are insoluble in water.
 High drug loading can be achieved as the drug exists in the form of pure solids, and can significantly reduce the
administration volume of high dose.
 It can increase the physical and chemical stability of drugs as they are actually in the solid state.
 Nanosuspensions can provide the passive targeting.
 Improved biological performance by increasing dissolution velocity and saturation solubility of drug2.
Aceclofenac is an NSAID. It is of synthetic origin and is a derivative of Phenylacetic acid. The molecular weight of
aceclofenac is 354.18. Half-life of the drug is 4hrs.
It is practically insoluble in water; freely soluble in acetone, soluble in ethanol 95%.
It is used for the relief of pain and inflammation in rheumatoid arthritis, osteoarthritis and ankylosingspondilytits.
It blocks the action of a substance in the body (cyclo-oxygenase), which may cause pain, swelling and
inflammation. It is contra-indicated in pregnancy and breast-feeding5.
Structure of Aceclofenac:
IUPAC name: 2-[2-[2-[(2, 6-dichlorophenyl)amino]phenyl]acetyl]oxyacetic acid.
The poor water solubility of the drug makes it an ideal candidate for formulation of nanosuspension.
6.2REVIEW OF LITERATURE:
 From the formulation development of Aceclofenacnanosuspension by 32 factorial design, it was concluded that
the preparation of nanosuspension of aceclofenac was simple and reproducible. The formulations were
optimised by using design of experiments by using 32 factorial statistical design and design expert software.
The amount of polymer and surfactant showed substantial effect on particle size. In vivo (animal) studies
showed the efficacy of the optimised formulation6.

Nanosuspension to enhance bioavailability of poorly soluble drugs was developed and it was concluded that
poor aqueous solubility is rapidly becoming the leading hurdle for formulation scientists working on drug
delivery of various drug compounds and leads to employment of novel formulation technologies.The use of
drug nanosuspension is a universal formulation approach to increase the therapeutic performance of these drugs
in any route of administration. Almost any drug can be reduced in size to the nanometer range. Production
techniques such as media milling and high pressure homogenization have been successfully employed for largescale production of nanosuspensions7.

In a study, formulation and evaluation of nanosuspension was carried out and it was concluded that
nanosuspension appear to be a unique & yet commercially viable approach to combating problems such as poor
bioavailability that are associated with the delivery of hydrophobic drugs, including those that are poorly
soluble in aqueous as well as organic media. Production techniques such as media milling & high pressure
homogenization have been successfully employed for large scale production of nanosuspensions8.

Nanosuspension technology was designed for solubilising poorly soluble drugs and concluded that
nanosuspensions are chiefly seen as vehicles for administering poorly water soluble drugs have been largely
solved the dissolution problems to improve drug absorption and bioavailability. It has many formulations and
therapeutic advantages, such as simple method of preparation, less requirement of excipients, increased
dissolution velocity and saturation solubility, improved adhesion, increases the bioavailability leading to a
decrease in the dose and fast-fed variability and ease of large-scale manufacturing. Many drug delivery and
pharmaceutical companies are exploiting this technology to re-examine active ingredients that were abandoned
from formulation programs because of their poor solubility9.

Formulation and Optimization of Nanosuspensions for enhancing Simvastatin dissolution using Central
Composite Design was done and results showed thatSimvastatin nanosuspension can be prepared using a wetmilling method with Pluronic F127 as hydrophilic polymer stabilizer at the laboratory scale. In experimental
design, careful selection of the amount of ZrO2 beads and Pluronic F127 as stabilizer are critical to achieve a
particle size close to 350 nm. Greater than 60% drug dissolved in 10 min. Nanosized simvastatin dissolved
much more rapidly than the micronized form. Clearly, these results indicate the suitability of the formulation
procedure for the preparation of simvastatin nanosuspension with significant improvement of the in vitro
dissolution rate, and thus possibly improved oral bioavailability10.

Formulation and characterization of chitosan nanoparticles loaded with rizatriptan benzoate was studied. It
showed that Rizatriptan benzoate nanoparticles were prepared successfully using ionic gelation method. The
drug: polymer ratio was found to influence the % entrapment efficiency and release characteristics of
nanoparticles. Polymer and drug was found to be compatible. It was concluded that mucoadhesive nanoparticles
as intranasal formulation is an alternative drug delivery system for nose to brain transport11.

Formulation of itraconazolenanosuspension for oral delivery was studied for in vitrocomparison with marketed
formulation. Result showed that nanocrystalline suspensions of poorly soluble drugs such as itraconazole are
easy to prepare and to lyophilize for extended storage and represent a promising new drug formulation for oral
drug delivery for treatment of fungal infection. Dissolution study in 0.1N HCl shows that nanosuspension
formulation gives higher drug release compared to the pure drug and marketed formulation. Consequently
nanosuspensions represent a promising alternative to current delivery systems aiming to improve the
biopharmaceutic performance of drugs with low water solubility12.

LoteprednolEtabonatenanosuspension was formulated by precipitation method for ophthalmic drug delivery
system. In this work the use of 32 factorial designs were demonstrated in optimizing formulation variables for
the preparation of Loteprednoletabonatenanosuspension by precipitation technique at laboratory scale and
evaluated for particle size, zeta potential, saturated solubility and dissolution study. This methodology could
therefore be employed successfully to nanosizing of the drug. The nanosuspension formulation was stable for 1
month at various conditions. The practical work resulted in the significant enhancement of solubility of
LoteprednolEtabonate in Simulated tear fluid (STF-pH-8) using Nanosuspension approach13.

Nanosuspension of cyclosporine was formulated and invitro comparison with marketed formulation was carried
out. From the results it was concluded that the present investigation of nanosuspension formulation containing
CsA can bean alternative dosage form of intravenous microemulsion formulation by avoiding a hypersensitivity
reaction caused by Cremophore EL 35. All Pharmacokinetic parameters show favourable results. It can
modulate the disposition of drug in the body and potentially improve the safety & efficacy profile of drug.Based
on result, it was a simple, cost effective and scalable method as compared to other methods14.
6.3Objectives of study:
The objective of the study is as follows
1. To carry out identification and preformulation study of drug and selected polymers.
2. To formulate nanosuspension.
3. Evaluation of formulated nanosuspension for various parameters like:
 Particle size analysis and shape morphology.
 Entrapment efficiency.
 Drug content estimation.
 Zeta potential.
4. To carry out in vitro dissolution studies of aceclofenacnanosuspension.
5. To carry out stability studies on the most satisfactory formulation.
b)material and methods
7.1 MATERIAL:
Drug-Aceclofenac.
Polymers- Biodegradable/non biodegradable.
Solvent-water, ethanol, acetone etc
7.2 METHODS OF PREPARATION:
1) Wet Milling
2) Homogenization
3) Homogenization in Non aqueous Media (Nanopure)
4) Combined Precipitation and Homogenization (Nanoedege)
Characterisation of nanosuspension:
1) Particle size distribution
2) Crystal morphology
3) Zeta potential
4) Dissolution velocity and saturation solubility
Evaluation:
1) In vitro drug release studies
2) Saturation solubility studies
3) Wettability study
4) Permeation study
7.3 Source of data:
Preliminary data required for experimental study would be obtained from,
 Literature review, pub med, med line, science direct.
 International Journals such as International Journal of Universal Pharmacy and Life Sciences,International
Journal of Drug Development & Research,International Journal of Pharma and Bio Sciences
7.5 Method of collection of data:
The physicochemical properties of the drug will be collected from various standard books, international journals,
website, literature research etc.
The experimental data will be collected from prepared formulation by subjecting formulation to different evaluation
parameter like in vitro drug release studies, Saturation solubility studies, Wettability study, and Permeation study.
7.6 Does the study require any investigation or interventions to be
Conducted on patients or other humans or animals?
NA
7.7 Has ethical clearance been obtained from your institution in case of 7.6?
NA
c)list of references
1. Kaur J, Aggarwal G, Singh G, Rana AC. Improvement of drug solubility using solid dispersion. IJPPS.
2012; 4(2): 1-7.
2. Bala Krishna K.A review on nanosuspension in drug delivery. IJPBS. Jan-March 2011; 2(1).
3. Patel M, Shah A, Patel NM, Patel MR, Patel KR.Nanosuspension: a novel approach for drug delivery
system. JBSPR. July-August 2011; 1(1): 1-10.
4. Nagaraju P, Krishnachaithanya K, Srinivas VDN, Padma SVN, Nanosuspensions: A promising drug
delivery system. IJPSN. Jan –Mar 2010; 2(4).
5. Druginfosys.com. 2013. PharmacoKinetics of Aceclofenac. [online] Available at:
http://druginfosys.com/Drug.aspx?drugCode=1792&drugName=Aceclofenac&type=2 [Accessed: 19 Dec
2013].
6. JorwekarP,Pathak A A,Chaudhari ,Formulation development of aceclofenac loaded nanosuspension by 32
factoraildeign.IJPSN.2012;4(4):
7. Paun JS, Tank HM. Nanosuspension: An Emerging Trend for Bioavailability Enhancement of Poorly
Soluble Drugs.Asian J. Pharm. Tech. 2012; 2(4): 157-168.
8. VB Patravale, Abhijit A, RM Kulkarni. Nanosuspensions: a promising drug delivery strategy. JPP. 2004;
(56): 827–40
9. DeoliMukesh. Nanosuspension technology for solubilizing poorly soluble drugs. IJDDR. OctoberDecember 2012; 4(4):
10. Pandya VM, Patel JK, Patel DJ. Formulation and Optimization of nanosuspensions for enhancing
simvastatin dissolution using central composite design. Dissolution technologies. August 2010.
11. Jadhav SS, Bhalerao AV. Formulation and characterization of chitosan nanoparticles loaded with rizatriptan
benzoate. Der PharmaciaLettre. 2013; 5(4): 218-223.
12. Nakarani M, Misra AK, Patel JK, Vaghani SS. Itraconazolenanosuspension for oral delivery: Formulation,
characterization and in vitro comparison with marketed formulation.DARU. 2010; 18(2) .and Optimization
of nanosuspensions for enhancing simvastatin dissolution using central composite
design,Dissolutiontechnologies;August 2010.
13. Memon. A, Patel. P.U, Sheth. H M, Patel. D. Formulation, Optimization and Characterization of
LoteprednolEtabonatenanosuspension by precipitation method for opthalmic drug delivery system. IJPFR
Jan-March 2013; 3(1): 42-53.
14. Mahendra N, Priyal P, Jayvadan P, Pankaj P, Rayasa SRM, Subhash SV,Cyclosporine A- Nanosuspension:
Formulation, characterisation and in vivo comparison with a marketed formulation. Sci Pharm. 2010; 78:
345–361.
15. Saag MS, Dismukes WE. Azole antifungal agents: emphasis on new triazoles. Antimicrobial Agents
Chemother. 1988; 32:1–8.