This document discusses nanocapsules, which are vesicular drug delivery systems containing an inner liquid core surrounded by a polymeric membrane between 250-500 nm in diameter. Nanocapsules offer advantages like higher drug loading, protection from degradation, and controlled drug release. They can be prepared using methods like nanoprecipitation, emulsion diffusion, double emulsification, and layer-by-layer assembly. Characterization techniques evaluate properties such as particle size, drug content, and in vitro drug release. Nanocapsules have applications for oral, parenteral, and ocular drug delivery.

1. NANOCAPSULES:
By- Kushal Saha (MPH/10008/19)

2. What is Nanocapsule?
• Nano capsules are vesicular systems in which the drug is confined to a
cavity consisting of an inner liquid core surrounded by a polymeric
membrane. The diameter of the drug particles should be in range of 250-
500 nm.
• They are colloidal nano-bubbles in which the core (oily or aqueous) is
surrounded by a polymeric membrane with specific properties.
• It is a characteristic class of nanoparticles, are made up of one or more
active materials (core) and a protective matrix (shell) in which the
therapeutic substance may be confined.
• Nano capsules have been developed as drug delivery systems for several
drugs by different routes of administrations such as oral and parental
with pH range of 3.0-7.5

3. Advantages Of Nanocapsules
• Higher dose loading
• Reduce irritation of drug at site of administration.
• Greater protection from degradation during storage & after
administration.
• Site specific action.
• Increase bioavailability of drug.
• Control and sustain release of the drug at the site of localization.
• The system can be used for various routes of administration
including oral, nasal, parenteral, intra-ocular etc.
• Improve patient compliance.

4. Structure of Nanocapsules

5. Preparation

6. Nanoprecipitation Method
General Formula:
Material Suggested Composition
Active Sub. 10-25mg
Polymer 0.2-0.5% of solvent
Oil 1.0-5.0% of solvent
W/O surfactant 0.2-0.5% of solvent
Solvent 25ml
Stabilizer 0.2-0.5% of solvent
Non solvent 50ml

7. Emulsion Diffusion Method
General Formula:
Material Suggested Composition
Active Sub. 10-50mg
Polymer 1-2% of solvent
Oil 2.5-5% of solvent
Inner phase Solvent 10ml
Stabilizer 2-5% of solvent
External phase
Solvent
200ml

8. Double Emulsification Method
General Formula:

9. Emulsion Co-acervation Method

10. Polymer Coating Method

11. Layer-By-Layer Method
 The layer-by-layer assembly process developed for colloidal particle preparation makes it
possible to obtain vesicular particles called polyelectrolyte capsules. This method requires a
colloidal template onto which is adsorbed a polymer layer either washed (or) by decreasing
polymer solubility by drop-wise addition of a miscible solvent.
 As reported in different research works the layer-by-layer method makes used of polycations
such as polylysine, Chitosan, gelatin-B, poly(ally amine) (PAA), poly(ethyleneimine) (PEI),
aminidextran and protamine sulfate. The polyanion are sodium alginate , poly (styrene
sulfonate) (PSS),poly(acrylic acid), dextran sulfate carboxy methylcellulose, haluronic acid,
gelatin-A, chondroitin and heparin.
Artemisin

12. Characterization/
Evaluation Of Nanocapsules
1) DETERMINATION OF THE PH OF NANOCAPSULE
Nano capsules formulation pH was measured using a digital pH meter at room temperature. Nano capsules
dispersion pH values fall within a range of 3.0-7.5.
2) MEAN NANO CAPSULES
The mean particle size of nanocapsules prepared from performed polymers are in general between 250-
500nm. In double emulsification method has concluded that particle size depends on the internal and external
surfactants that determine droplet size, the interaction at the interface and the structural conformation of the
nano capsules wall.
3) DETERMINATION OF DRUG CONTENT
Drug content was determined by dissolving 1ml of prepared nanocapsules in 20ml of acetonitrile. Appropriate
quantity of sample was then subjected to the UV Spectrophotometer at 232nm. The absorbance for each
sample was measured and compared with the standard.

13. Characterization/
Evaluation Of Nanocapsules
4) PARTICLE SIZE DISTRIBUTATION AND PARTICLE CHARGE/ZETA POTENTIAL
Particle size distribution is an important aspect during the formulations of nano systems. Nano capsules
were characterized for their particle size distribution and zeta potential using Malvern zetasizer.
5) STRUCTURAL CHARACTERIZATION
Structural characterization can be done by using field emission scanning electron microscopy (FE-SEM) and
transmission electron microscopy (TEM) to determine the various attributes like shape, size and surface
morphology. Micrographs of the nanocapsules were obtained using a Phillips Cm 200 operated at 20-200 kv
while the Fe-SEM was carried out using Hitachi S-4800 FE-SEM equipped with energy dispersion
spectrometer (EDS).
6) IN-VITRO DRUG RELEASE
In vitro dissolution studies were carried out using USP type 11 dissolution apparatus. The study was carried
out in 100 ml of buffer (PH 3.0). the nanocapsules suspension was placed in dialysis membrane and dipped
in dissolution medium which was kept inert thermostatically at 37±0.50C. The stirring rate was maintained
at 100 rpm. At predetermined time intervals 5ml of sample were withdrawn and assessed for drug release
spectrophotometrically. After each withdrawal 5 ml of fresh dissolution medium was added to dissolution
jar.

14. Applications
 ORAL ROUTE
 Indomethacin an anti-inflammatory drug has been successfully encapsulated in
the poly alkylcyanoacrylate nano capsules with the aim of reducing its side
effect on the gastric and intestinal mucosa.
 Diclofenac and Indomethacin two major non-steroidal anti-inflammatory
agents, have been encapsulated in poly(lactic acid) nano capsules obtained by
nano precipitation with the aim of reducing their side effects on the gastric
mucosa.
 Insulin-loaded nano capsules yielded promising pharmacological results.
 Anti infectious agents such as Atovaquone and Rifabulin, two compounds active
against the opportunituistic parasite Toxoplasma gondil, were successufully
entrapped in poly (lactide) nano capsules formed by nano precipitation.

15. Applications
 PARENTERAL ROUTE
 As far as the parenteral route is concerned, nanocapsules could be useful for the formulation of
poorly soluble drugs and for controlling the drug distribution according to properties of the
carrier.
 Nano capsules prepared by interfacial polymerization of the iso butyl cyano acrylate monomers
were retained longer at the injection site after intra muscular administration that the other types
of carriers such as emulsion (or) liposomes.
 An antimalarial drug Halofantrine was entrapped with the aim of obtaining a well- tolerated
injectable form for the treatment of this sever intravascular disease.
 OCULAR DELIVERY:-
 Betaxolol-loaded poly (iso butyl cyano acrylate) nanocapsules made by interfacial polymerization
were prepared for the treatment of glaucoma.
 Ganciclovir encapsulation in poly (ethyl ayano acrylate) nanocapsules made by interfacial
polymerization provided a sustained release of the drug over four days.
 Ganciclovir is an antiviral drug used for the treatment of cytomegalovirus infections.

16. Disadvantages
1) Extensive use of poly vinyl alcohol as a detergent issues with toxicity.
2) Limited targeting abilities.
3) Discontinuation of therapy is not possible.
4) Alveolar inflammation.
5) Cytotoxicity.
6) Pulmonary inflammation And pulmonary carcinogenicity.
7) The disturbance of autonomic imbalance by Nano particles having
direct effect on heart and vascular function.

17. Conclusion
The main goal of this review was to describe the different preparation
techniques available for production of polymeric nanoparticals. The drug
loaded Nanosphere/nanocapsules now can be produced by simple, safe and
reproducible technique available.
 Nano particle preparation methods have been marked by THREE
aspects:
 Need for lees toxic reagents.
 Simplification of the procedure to allow economic scale up.
 Optimization to improve yield and entrapment efficiency.