Nanosuspensions are colloidal dispersions of drug particles below 1 micron in size, stabilized by surfactants. They can improve the dissolution rate and bioavailability of poorly water soluble drugs compared to conventional formulations. The document discusses the definition, advantages, preparation techniques including high pressure homogenization and media milling, characterization, and applications of nanosuspensions through various routes of administration such as oral, intravenous, and ocular. Nanosuspensions reduce issues associated with poorly soluble drugs like low bioavailability and lack of dose proportionality.

1. By : Ms. Rutuja Dhorje
M.Pharm First Year (Pharmaceutics)
SEMESTER – I
Roll no. 05
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2. • What are Nanosuspensions?
• Need of Nanosuspensions
• Major Advantages of Nanosuspensions
• Advantages of Nanosuspensions over Conventional Formulations
• Stability Issues
• Formulation considerations
• Preparation Techniques of Nanosuspensions
• Characterization and Evaluation
• Application
• Marketed Preparation
• Case Study
• Conclusion
• Bibliography
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3. • A pharmaceutical nanosuspension is defined as :
“Very finely colloid biphasic, dispersed and solid drug particles in aqueous vehicle,
size below 1um without any matrix material stabilized by surfactant and polymers and
prepared by suitable methods for drug delivery applications through various routes of
administration.”
• Average particle size ranges from 200-600 nm.
(The diameter of suspended particle is usually less than 1 μm in size).
• An increase in the dissolution rate of micronized particles (particle size < 10 μm) is
related to an increase in the surface area and consequently the dissolution velocity.
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4. • Major issues associated with poorly water soluble drugs:
1. Poor bioavailability.
2. Inability to optimize lead compound selection based on efficacy and safety
3. Fed/fasted variation in bioavailability
4. Lack of dose-response proportionality
5. Suboptimal dosing
6. Use of harsh excipients, i.e., excessive use of co-solvents and other excipients
7. Use of extreme basic or acidic conditions to enhance solubilization
• Nanosuspension is the only approach universally applicable to overcome these issues
by enhancing solubility of drug in aqueous as well as lipid media.
• Thus preferred suitable for compounds with
high log P value
high melting point
high dose
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5. • Applicable for the poorly water soluble drugs.
• Reduced tissue irritation in case of subcutaneous/intramuscular administration.
• Rapid dissolution and tissue targeting can be achieved by IV route of administration.
• Oral administration provide rapid onset, reduced fed/fasted ratio and improved
bioavailability.
• Higher bioavailability and more consistent dosing in case of ocular administration and
inhalation delivery.
• Improvement in biological performance due to high dissolution rate and saturation
solubility of the drug.
• Long term physical stability (Due to absence of Ostwald ripening).
• Nanosuspensions can be incorporated in tablets, pellets, hydrogel and suppositories
are suitable for various routes of administration.
• Increasing the amorphous fraction in the particles, leading to a potential change in the
crystalline structure and higher solubility.
• Possibility of surface-modification of nanosuspension for site specific delivery.
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Route of administration Disadvantages of
Conventional Formulations
Benefits of Nanosuspensions
1. Oral Slow onset of action/ poor
absorption
Rapid onset of action/
improved solubility so
improved bioavailability.
Reduced fed/fasted ratio
2. Ocular Lacrimal wash off/ low
bioavailability
Higher bioavailability/ dose
consistency. Lesser irritation
3.Intravenous Poor dissolution/ non-specific
action
Rapid dissolution/ tissue
targeting. Prolonged retention
time in systemic circulation
4. Intramuscular Low patient compliance due to
pain
Reduced tissue irritation High
bioavailability. Rapid onset of
action
5. Inhalational Low bioavailability due to low
solubility
Rapid dissolution/ high
bioavailability/ dose regulation

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a- deflocculated suspension
b- deflocculated suspension
c- open-flocs based suspension

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Excipient Function Example
1. Stabilizer Wet the drug particles thoroughly,
prevent Ostwald’s ripening and
agglomeration of
nanosuspensions, providing steric
or ionic barrier.
Lecithins, Poloxamers,
polysorbates, cellulosics,
povidones.
2. Co-surfactant Influence phase behaviour when
micro emulsions are used to
formulate nanosuspensions.
Bile salts, dipotassium
glycerrhizinate, transcutol,
glycofural, ethanol, isopropanol
3. Organic Solvent Pharmaceutically acceptable, less
hazardous solvent for preparation
of formulation
Methanol, ethanol, chloroform,
isopropanol, ethyl acetate, ethyl
formate, butyl lactate, triacetin,
propylene carbonate, benzyl
alcohol
4. Other additives According to the requirement of
the route of administration or
properties of the drug moiety.
Buffers, salts, polyols, osmogens,
cyroprotectants, etc.

9. • Homogenization in water (DissoCubes)
• Media Milling (Nanocrystals or Nanosystems)
• Homogenization in non-aqueous media (Nanopure)
• Combined precipitation and homogenization (Nanoedge)
• Nanojet Technology
• Emulsification-Solvent Evaporation Technique
• Hydrosol Method
• Supercritical Fluid Method
• Dry Co-grinding
• Emulsion as template
• Microemulsion as template
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In bottom-up Technology, the drug is dissolved in an organic solvent and this solution is mixed with a
miscible anti-solvent. In the water-solvent mixture, the solubility is low and the drug precipitates. Basic
challenge is that during the precipitation procedure growing of the crystals need to be controlled by
addition of surfactant to avoid formation of microparticles.
In Top-down Technology, the nano size range of
particles is obtained by reduction in size of
larger particles.

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12. • This patent-protected technology was developed by Liversidge et al. (1992). Formerly,
the technology was owned by the company NanoSystems but recently it has been
acquired by Élan Drug Delivery.
• The milling chamber charged with polymeric media is the active component of the mill.
• Operated in batch or recirculation mode.
• Crude slurry consisting of drug, water and stabilizer is fed into the milling chamber
and processed into nano-crystalline dispersion and the milling media or pearls are
then rotated at a very high shear rate.
• The typical residence time generated for a nanometer-sized dispersion with a mean
diameter of <200nm is 30–60 min.
• Principle:
The high energy and shear forces generated as a result of the impaction of the
milling media with the drug provide the energy input to break the microparticulate drug
into nano-sized particles.
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Elan Lab Scale NanoMill TM for
batch production of Nanosuspensions.
Schematic of wet bead milling process used for production of
drug nanoparticles

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ADVANTAGES
• Drugs that are poorly soluble in both aqueous and organic media can be easily formulated
into nanosuspensions.
• Ease of scale-up and little batch-to-batch variation.
• Narrow size distribution of the final nanosized product.
• Flexibility in handling the drug quantity, ranging from 1 to 400mg/mL, enabling formulation
of very dilute as well as highly concentrated nanosuspensions
DISADVANTAGES
• Generation of residues of milling media, which may be introduced in the final
product as a result of erosion.
• Scale up is not easy due to mill size or weight.
• Time consuming

15. • Most widely used method for preparing nanosuspensions of many poorly soluble
drugs,
• Basically involves three steps:
1. Initially, drug powders are dispersed in stabilizer solution to form pre-suspensions.
2. Secondly, the pre-suspension is homogenized in High Pressure Homogenizer at a
low pressure for pre-milling.
3. Finally it is homogenized at high pressure for 10-25 cycles until the
nanosuspensions of desired size are formed.
• DissoCubes technology is an example of this technology developed by R.H. Muller in
1999 e.g. Omeprazole.
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Scanning electron microscope
image of a nanosuspension prepared
with High Pressure Homogenization

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Basic principle:
1. Particle size reduction is based on the cavitation
principle.
2. The dispersion contained in 3cm diameter
cylinder; suddenly passes through a very narrow
gap of 25µm.
3. This leads to increase in dynamic pressure and
decrease of static pressure below the boiling
point of water at room temperature.
4. Due to this, water starts boiling at room
temperature and forms gas bubbles, which
implode when the suspension leaves the gap
(called cavitation) and normal air pressure, are
reached.
Factors affecting size of drug nanocrystals:
1. Temperature
2. Number of homogenization cycles
3. Power density of Homogenizer
4. Homogenization pressure

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ADVANTAGES
• It does not cause the erosion of processed materials.
• Very dilute as well as highly concentrated nanosuspensions can be prepared by
handling 1mg/ml to 400mg/ml drug quantity.
• It is applicable to the drugs that are poorly soluble in both aqueous and organic
media.
• It allows aseptic production of nanosuspensions for parenteral administration.
DISADVANTAGES
• Pre-processing like micronization of drug is required.
• High cost instruments are required that increases the cost of dosage form.

19. • Nanosuspensions are characterized for appearance, color, odour, assay, related
impurities, particle size, zeta potential, crystalline status, dissolution studies and in
vivo studies.
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Evaluation of
nanosuspensions
In-Vitro
Evaluation
1. Particle size and
distribution
2. Particle charge (Zeta
Potential)
3. Crystalline state and
morphology
4. Saturation Solubility and
Dissolution rate
5. Solubility
In-Vivo
Evaluation
Evaluation of
surface modified
1. Surface
hydrophilicity.
2. Adhesion
properties.
3. Interaction with
body proteins.

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22. • The efficacy or performance of the orally administered drug generally depends on its
solubility and absorption through the GIT.
• Nano-sizing of such drugs can lead to a dramatic increase in their oral absorption and
subsequently bioavailability.
• The amelioration in oral bioavailability can be attributed to the adhesiveness of the
drug nanosuspension, increased surface area (due to reduction in particle size by 10–
50 fold), and increased saturation solubility, leading to an increased concentration
gradient between the gastrointestinal tract lumen and blood, and increased dissolution
velocity.
• This enhancement in bioavailability will lead to a subsequent reduction in drug dose,
rendering the therapy cost-effective and obliterating any undue drug dumping in the
body.
• Danazole, a poorly bioavailable gonadotropin inhibitor, showed a drastic improvement
in bioavailability when administered as a nanosuspension as compared to the
commercial Danazole macrosuspension Danocrine.
Danazole nanosuspension led to an absolute bioavailability of 82.3%, whereas the
marketed Danazole suspension Danocrine was 5.2% bioavailable. In addition,
Danazole nanosuspension resulted in a reduction in the inter-subject variability and
fed/fasted ratio of Danazole.
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23. • Nanosuspensions overcome the problems of solubilization capacity, parenteral acceptability,
physical instability, high manufacturing cost and difficulties in scale-up as in other parenteral
formulations.
• Nanosuspensions reduce the cost of therapy and improve therapeutic performance of drug by
improving the parentally tolerable dose of drug.
• Clofazimine nanosuspension shows improved stability and efficacy when compared to the
liposomal Clofazimine in M. avium-infected female mice.
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PULMONARY DRUG
DELIVERY• Drugs that are poorly soluble in pulmonary secretions can be administered by the formulation of the
nanosuspensions.
• These drugs are delivered as suspension aerosols or as dry powders by means of dry powder
inhalers.
• Nebulized form of the aqueous nanosuspensions is used for the delivery of drugs to lung.
• Bupravaquone nanosuspensions formulated by nebulization. Nanosuspension of Budesonide has
also been prepared successfully for pulmonary delivery.

24. • Nanosuspension is an ideal approach for ocular delivery of hydrophobic
drugs as they improve the saturation solubility of the drug.
• Nanosuspensions of glucocorticoid drugs; hydrocortisone, prednisolone and
dexamethasone show improved shelf-life and the bioavailability after
ophthalmic application due to enhanced rate of drug absorption.
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DRUG
TARGETTING• As the surface properties and in-vivo behaviour of nanosuspensions can be altered easily
by changing either the stabilizer or the milieu, so they are good candidates for targeted
delivery.
• Brain targeting of peptide Dalargin has been done successfully by the modification of the
nanoparticle surface using poly-isobutyl cyanoacrylate.

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Parenteral Liquid
Nanosuspension
Johnson & Johnson
High Pressure Homogenization
For schizophrenia
Lyophilized powder for injectable
suspensions
Abraxis Bio-sciences
nab™
Metastatic Breast cancer
Oral Liquid Nanosuspension
Par Pharmaceutical
Media Milling
Appetite Stimulant

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Overview of the technologies and patents / patent applications on which the various
homogenization processes are based

28. • Title: Development and Characterization of Mucoadhesive Nanosuspension of
Ciprofloxacin
• Reference: VIKAS JAIN*, PRADEEP KARE, DEEPIKA JAIN and RANJIT SINGH,
Development and Characterization of Mucoadhesive Nanosuspension of Ciprofloxacin,
Acta Poloniae Pharmaceutica - Drug Research, Vol. 68 No. 2 pp. 273- 278.
• Abstract: Mucoadhesive nanosuspension of ciprofloxacin was designed to improve its
solubility, bioavailability and efficacy in the treatment of typhoid fever. After development,
characterization of ciprofloxacin nanosuspension was performed to conclude that it
exhibited satisfactory physical stability and can be effectively formulated as novel
gastroretentive drug delivery systems .
• Result:
The system exhibited enhanced dissolution rate due to decreased particle size.
The incorporation mucoadhesive polymers can increase the gastric residence time of the
ciprofloxacin resulting in an efficient system. The enhanced residence time in
gastrointestinal tract may decrease the dosing frequency as well as dose of drug.
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29. • Title: Analytical Evaluation of formulated Occular Nanosuspension of Pilocarpine
Nitrate
• Reference: Kalpana Anumolu*, Vijay Amritharaj R, Suchetha Reddy Aleti and N.
Senthil Kumar, Analytical Evaluation of Formulated Occular Nanoasuspension of
Pilocarpine Nitrate, International Journal Of Research In Pharmacy And Chemistry.
• Abstract: Ophthalmic nanosuspension of Pilocarpine nitrate was prepared by quassi
emulsion method using Eudragit S 100 and was evaluated for pH, entrapment
efficiency, UV, Drug polymer compatibility by FT-IR and DSC. The readings obtained
showed that the percentage drug entrapment efficiency was ranged between 65-80%.
DSC studies were carried out for pure drug and physical mixture of pure drug with
polymer; data from DSC study conclude that there were no drug polymer interactions
between the drug and polymer combinations.
• Result: Results obtained were within the limits indicating the proposed method for the
formulation is good for single dosing and validation results were accurate and precise.
Also the prepared ocular nanosuspension have a pH of 6.4-7.4 (Eye have a tolerable
capacity of 5-7.4 pH)
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30. • Despite of stability problems, Nanosuspensions appears to be a unique and yet
commercially viable approach to combating various 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.
• Attractive features, such as increased dissolution velocity, increased saturation
solubility, improved bio-adhesiveness, versatility in surface modification and ease of
post-production processing, have widened the applications of nanosuspensions for
various routes.
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31. • NANOSUSPENSION: A PROMISING DRUG DELIVERY SYSTEM Geeta Vikram
Yadav* and Sushma R. Singh. http://www.pharmacophorejournal.com/
• Katteboinaa S, Drug nanocrystals: A novel formulation approach for poorly Soluble
drugs, International journal of pharmtech research, 1(3), 2009, 682-694.
• Dineshkumar B, Nanosuspension Technology in Drug Delivery System, Nanoscience
and Nanotechnology: An International Journal, 3(1), 2013, 1-3.
• Patel AP, A review on drug nanocrystal a carrier free drug delivery, IJRAP, 2(2), 2011,
448-458.
• Dhiman S, Nanosuspension: a recent approach for nano drug delivery system,
International journal of current pharmaceutical research, 3, 2011, 96-101.
• Basics about nanosuspensions and current research in the field - for pharmacy, Rahil
Dalal, Published in: Health & Medicine, www.slideshare.net.
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