NOVEL DRUG DELIVERY SYSTEM

 

Characteristic features of polymers:  A polymer used in controlled drug  delivery formulations, must be:

  • Chemically inert
  • Non-toxic
  • Free of leachable impurities
  • An appropriate physical structure
  • With minimal undesired aging
  • Readily processable

Abraxane is the first polymeric nanoparticle based product from American  Pharmaceutical Partners, Inc., and American Bioscience, Inc. (ABI). It was  approved in year 2005 and is consisting of albumin-bound paclitaxel  nanoparticles. This product is free of toxic solvents like cremophor-EL, M which is used until now to solubalize paclitaxel in order to administer it
intravenously to the patient. cremophor-EL is known to cause life-threatening allergic reactions.  Success of Abraxane show that nanotechnology can bring many exciting products which can overcome many hurdle of formulation scientist.

3.4 PREPARATION TECHNIQUES OF NANOPARTICLES:
The selection of appropriate method for the preparation of nanoparticles depend on the physicochemical characteristics of the polymer and the drug to be loaded. On the contrary, the preparation techniques largely determine the inner structure, in vitro release profile and biological fate of these polymeric delivery systems. Two type of system with different inner structure are apparently possible including:
·         MATRIX TYPE SYSTEM: This consisting of  an entanglement of oligomer or polymer units (nanoparticles / nanospheres ).

·         RESERVOIR TYPE SYSTEM: This comprised of an oily core surrounded by an embryonic polymeric shell(nanocapsules).

The drug can either be entrapped within the reservoir or the matrix or otherwise be absorbed on the surface of these particulate systems. The polymers are strictly structured  to a nanometric size range particle using appropriate methodologies. These  methodologies are conveniently classified as follows:
I.            AMPHIPHILIC MACROMOLECULE CROSS-LINKING:
a)      Heat cross-linking
b)      Chemical cross-linking
c)      Emulsion chemical dehydration
d)     Phase separation in aqueous medium (Desolvation)
e)      PH-induced aggregation
f)       Counter ion induced aggregation

II.            Polymerization based methods:
a)      Polymerization of monomers

b)      Emulsion (micellar) polymerization
1.      Conventional emulsion polymerization
·         Micellar nucleation and polymerisation
·         Homogenous nucleation and polymerization

2.      Inverse emulsion polymerization
c)      Dispersion polymerization
d)     Interfacial condensation polymerization
e)      Interfacial complexation

III.            POLYMER PRECIPITATION MEYHODS
a)      Solvent extraction /evaporation
b)      Solvent displacement(Nanoprecipitation)
c)      Salting out

AMPHIPHILIC MACROMOLECULE CROSS-LINKING:
The macromolecules used in the preparation are amphiphilic in nature means having capacity to contain both lipophilic and hydrophilic drugs. The preparation by this method involve the aggregation of amphiphiles and then cross-linking by heat or chemical cross-linking.
a)      Heat cross-linking
b)      Chemicalcross-linking

PROCEDURE:
NANOSPHERE PREPARATION BY CROSS LINKING OF AMPHIPHILIC MACROMOLECULES

Figure: 9 Heat denaturation process

Figure: 10 Chemical cross linking process

Figure: 11 Emulsion chemical dehydration process

(D) Phase separation in aquous medium:
The protein and polysaccharide from an aqueous phase Can be desolvated by PH

change, or change in temperature or by adding some appropriate counter ion.

PROCEDURE:   It involves three steps:
Step1: Proteine dissolution
Step2: Proteine aggregation
Step3: Proteine deaggregation

Figure: 12 Phase separation in aquous medium process

NANOPARTICLE PREPARATION USING POLYMERIZATION BASED
Two methods are generally used:
1)      Emulsion (micellar) polymerization: In which the monomer to be polymerized is emulsified in a non solvent phase.

GENERAL PROCEDURE OF EMULSIFICATION POLYMERISATION:
Step1: Monomer is emulsified in a non-solvent phase with surfactant molecule,then a monomer swollen micelle form

Step2: After the formation of micelles, polymerization takes place inside this. The two main process during polymerization are nucleation & propagation.

Step3: Reaction stop with the full consumption of the monomer & surfactant

Step4: We can add drug during the preparation or after the preparation.

If we add the drug in between the preparation,thy get encapsulated or dispersed in the matrix & if the drug is added after the preparation of the nanoparticles then they getadsorb to the surface of the nsanoparticles.

A) Conventional emulsion polymerization(O/W type): The emulsion is O/W type. The monomer is emulsified with the help of surfactant.

a)      Micellar nucleation and polymerization (used when monomer is slightly soluble in outer phase).

Figure: 13 Micellar nucleation and polymerization process

b)      Homogenous nucleation and polymerization (used when monomer is sufficiently soluble in outer phase)

Figure: 14 Homogenous nucleation and polymerization process

B) Inverse emulsion polymerization(W/O type)

Figure: 15 Inverse emulsion polymerization process

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