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Presented by:
Tanjila Hasan
Introduction
One of the major problems associated with poorly soluble drugs is very low
bioavailability. The problem is even more complex for drugs like itraconazole,
simvastatin, and carbamazepine which are poorly soluble in both aqueous and
non-aqueous media.
Nano-suspension which is an attractive and promising alternative to solve these
problems.
Nano-suspension
Nano-suspension are colloidal dispersion of nano-sized drug particle stabilized
by surfactant. The particle size of nano-suspension is less than 1 micrometer or
200-600 nm. Nano-suspension consists of the pure poorly water-soluble drug
without any matrix material suspended in dispersion. Preparation of nano-
suspension is simple and applicable to all drugs which are water insoluble. A
nano-suspension not only solves the problems of poor solubility and
bioavailability, but also alters the pharmacokinetics of drug and thus improves
drug safety and efficacy.
First nano-suspension product in market was RAPAMUNE, introduced in 2000
by company WYETH and the second product was EMEND in 2001 by MERCK
,for emesis.
Fig 1: Various kinds of Nano-suspensions
Fig 2: Nano-suspension under electron microscope
Features of Nano-suspension
 Small particle size: 300 nm to 10 microns.
 Low volume doses 10 – 200 mg/Ml.
 Safety increase because of co-solvent elimination thus increase dose.
 Long-term stability up to 2 years at room temperature or 5°C.
 Route for dosage form administration: IV injection, IM injection, ID injection,
oral, respiratory and other routes.
 Can be used for controlled and targeted delivery of drug.
Properties of Nano-suspension
1. Provide long term physical stability.
2. Adhesiveness.
3. Increase in saturation solubility and dissolution velocity of drug.
4. Provide passive targeting.
5. Provide versatility.
6. Enhance bioavailability.
Methods of Preparation of Nano-suspension
Ingredients Used in the Formulation of Nano-
suspension
 Stabilizer.
 organic solvents.
 Co-surfactant.
 other additives like buffers, salts, polyols, osmogents, and cryo-protectants.
Media milling and High Pressure
Homogenization are used for large
scale production of Nano-suspension
Media Milling
The nano-suspensions are prepared by using high shear media mills. The milling
chamber charged with milling media, water, drug & stabilizer which re rotated at very
high shear rate under controlled temperature for 2-7 days.
The milling medium is composed of glass, zirconium oxide or highly cross-linked
polystyrene resin. The high energy shear forces are generated as a result of impaction of
milling media with the drug resulting into breaking of micro-particulate drug to nano-
sized particles.
The major concern with this method is the residues of milling media remaining in the
finished product could be problematic for administration.
Fig 3: Media Milling
Advantages and Disadvantages of media
milling
Advantages:
 Applicable to the drugs that are poorly soluble in both aqueous and organic
media.
 Very dilute as well as highly concentrated nano-suspensions can be prepared
by handling 1mg/ml to 400mg/ml drug quantity.
Disadvantages:
 Nano-suspensions contaminated with materials eroded from balls may be
problematic when it is used for long therapy.
 The media milling technique is time consuming.
 Some fractions of particles are in the micrometer range.
 Scale up is not easy due to mill size and weight.
High Pressure Homogenization
It is most widely used method for preparing nano-
suspensions of many poorly aqueous soluble drugs. It
involves three steps.
• Firstly drug powders are dispersed in stabilizer solution
to form pre-suspensions.
• Secondly the pre-suspension is homogenized in high
pressure homogenizer at a low pressure for premilling.
• Finally homogenized at high pressure for 10 to 25 cycles
until the nano-suspensions of desired size are formed.
Fig 4: High Pressure Homogenization
Advantages :
 Low risk of product contamination.
 Allows aseptic production of nano-
suspensions for parenteral
administration.
Disadvantages:
 Prerequisite of micronized drug
particles.
 Prerequisite of suspension formation
using high-speed mixers before
subjecting it to homogenization.
Advantages and Disadvantages of High
Pressure Homogenizer
Fig 5: Machine of High Pressure Homogenization
Advantages and Disadvantages of Nano-
suspension
Advantages
↘ Can be applied for the water soluble drugs.
↘ Rapid dissolution and tissue targeting can
be achieved by IV route of administration.
↘ Oral administration of nano-suspension
provide rapid and improved bioavailability.
↘ Long term physical stability due to the
presence of stabilizer.
↘ Can be incorporated in tablets, pellets and
hydrogels.
Disadvantages
↗ Physical stability, sedimentation and
compaction can cause problems.
↗ It is bulky sufficient so care must b e taken
during handling and transport.
↗ Uniform and accurate dose cannot be
achieved unless suspension.
Pharmaceutical Applications of Nano-
suspension
 Oral Drug Delivery.
 Parental Administration.
 Ophthalmic Drug Delivery.
 Pulmonary drug Delivery.
 Target Drug Delivery.
Conclusion
Nano-suspension solved the poor bioavailability problems of poorly water as
well as organic soluble drugs. Media milling and High Pressure Homogenizer
are used for large scale production of Nano-suspension. Nano-suspension can
be administered through Oral, Parenteral, Pulmonary and Ocular routes. Nano-
suspension is simple, less requirements of excipients, increased dissolution rate
and saturation solubility.
References
1. International Journal of Pharma Research & Review, Sept 2014; 3(9):30-37.
2. Journal of Nanotechnology. Volume 2013 (2013), Article ID 346581, 12
pages.
3. J Adv Pharm Technol Res. 2011 Apr-Jun; 2(2): 81–87.
doi: 10.4103/2231-4040.82950.
Nanosuspension

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Nanosuspension

  • 2. Introduction One of the major problems associated with poorly soluble drugs is very low bioavailability. The problem is even more complex for drugs like itraconazole, simvastatin, and carbamazepine which are poorly soluble in both aqueous and non-aqueous media. Nano-suspension which is an attractive and promising alternative to solve these problems.
  • 3. Nano-suspension Nano-suspension are colloidal dispersion of nano-sized drug particle stabilized by surfactant. The particle size of nano-suspension is less than 1 micrometer or 200-600 nm. Nano-suspension consists of the pure poorly water-soluble drug without any matrix material suspended in dispersion. Preparation of nano- suspension is simple and applicable to all drugs which are water insoluble. A nano-suspension not only solves the problems of poor solubility and bioavailability, but also alters the pharmacokinetics of drug and thus improves drug safety and efficacy. First nano-suspension product in market was RAPAMUNE, introduced in 2000 by company WYETH and the second product was EMEND in 2001 by MERCK ,for emesis.
  • 4. Fig 1: Various kinds of Nano-suspensions
  • 5. Fig 2: Nano-suspension under electron microscope
  • 6. Features of Nano-suspension  Small particle size: 300 nm to 10 microns.  Low volume doses 10 – 200 mg/Ml.  Safety increase because of co-solvent elimination thus increase dose.  Long-term stability up to 2 years at room temperature or 5°C.  Route for dosage form administration: IV injection, IM injection, ID injection, oral, respiratory and other routes.  Can be used for controlled and targeted delivery of drug.
  • 7. Properties of Nano-suspension 1. Provide long term physical stability. 2. Adhesiveness. 3. Increase in saturation solubility and dissolution velocity of drug. 4. Provide passive targeting. 5. Provide versatility. 6. Enhance bioavailability.
  • 8. Methods of Preparation of Nano-suspension
  • 9. Ingredients Used in the Formulation of Nano- suspension  Stabilizer.  organic solvents.  Co-surfactant.  other additives like buffers, salts, polyols, osmogents, and cryo-protectants.
  • 10. Media milling and High Pressure Homogenization are used for large scale production of Nano-suspension
  • 11. Media Milling The nano-suspensions are prepared by using high shear media mills. The milling chamber charged with milling media, water, drug & stabilizer which re rotated at very high shear rate under controlled temperature for 2-7 days. The milling medium is composed of glass, zirconium oxide or highly cross-linked polystyrene resin. The high energy shear forces are generated as a result of impaction of milling media with the drug resulting into breaking of micro-particulate drug to nano- sized particles. The major concern with this method is the residues of milling media remaining in the finished product could be problematic for administration.
  • 12. Fig 3: Media Milling
  • 13. Advantages and Disadvantages of media milling Advantages:  Applicable to the drugs that are poorly soluble in both aqueous and organic media.  Very dilute as well as highly concentrated nano-suspensions can be prepared by handling 1mg/ml to 400mg/ml drug quantity. Disadvantages:  Nano-suspensions contaminated with materials eroded from balls may be problematic when it is used for long therapy.  The media milling technique is time consuming.  Some fractions of particles are in the micrometer range.  Scale up is not easy due to mill size and weight.
  • 14. High Pressure Homogenization It is most widely used method for preparing nano- suspensions of many poorly aqueous soluble drugs. It involves three steps. • Firstly drug powders are dispersed in stabilizer solution to form pre-suspensions. • Secondly the pre-suspension is homogenized in high pressure homogenizer at a low pressure for premilling. • Finally homogenized at high pressure for 10 to 25 cycles until the nano-suspensions of desired size are formed.
  • 15. Fig 4: High Pressure Homogenization
  • 16. Advantages :  Low risk of product contamination.  Allows aseptic production of nano- suspensions for parenteral administration. Disadvantages:  Prerequisite of micronized drug particles.  Prerequisite of suspension formation using high-speed mixers before subjecting it to homogenization. Advantages and Disadvantages of High Pressure Homogenizer
  • 17. Fig 5: Machine of High Pressure Homogenization
  • 18. Advantages and Disadvantages of Nano- suspension Advantages ↘ Can be applied for the water soluble drugs. ↘ Rapid dissolution and tissue targeting can be achieved by IV route of administration. ↘ Oral administration of nano-suspension provide rapid and improved bioavailability. ↘ Long term physical stability due to the presence of stabilizer. ↘ Can be incorporated in tablets, pellets and hydrogels. Disadvantages ↗ Physical stability, sedimentation and compaction can cause problems. ↗ It is bulky sufficient so care must b e taken during handling and transport. ↗ Uniform and accurate dose cannot be achieved unless suspension.
  • 19. Pharmaceutical Applications of Nano- suspension  Oral Drug Delivery.  Parental Administration.  Ophthalmic Drug Delivery.  Pulmonary drug Delivery.  Target Drug Delivery.
  • 20. Conclusion Nano-suspension solved the poor bioavailability problems of poorly water as well as organic soluble drugs. Media milling and High Pressure Homogenizer are used for large scale production of Nano-suspension. Nano-suspension can be administered through Oral, Parenteral, Pulmonary and Ocular routes. Nano- suspension is simple, less requirements of excipients, increased dissolution rate and saturation solubility.
  • 21. References 1. International Journal of Pharma Research & Review, Sept 2014; 3(9):30-37. 2. Journal of Nanotechnology. Volume 2013 (2013), Article ID 346581, 12 pages. 3. J Adv Pharm Technol Res. 2011 Apr-Jun; 2(2): 81–87. doi: 10.4103/2231-4040.82950.

Notes de l'éditeur

  1. Co-surfactant-  A surfactant acting in tandem with another surfactant to enhance its properties. Polyols- Polyols are sugar-free sweeteners. They are carbohydrates but they are not sugars. Ex: sorbitol. Osmogents- Osmogents are osmotic agents used for fabrication. Cryoprotectants- Cryoprotectants are substances used to protect biological tissue from freezing damage.