Professional Documents
Culture Documents
PHARMACEUTIC-II
(PHYSICAL PHARMACY)
SUBMITTED BY:
AAMIR NAWAZ
SESSION:
(2020-2021)
2nd A
STUDENT ID:
BPD02201039
SUBBMITED TO:
DR. ASIF MEHMOOD SB
Assistance professor of pharmaceutics
________________________________________________________
FACULTY OF PHARMACY
THE UNIVERSITY OF LAHORE
LAHORE, PAKISTAN
SOLUBILITY AND SOLUBILITY ENHANCEMENT
TECHNIQUES
SOLUBILITY:
Definition:
The term ‘‘solubility’’ is defined as maximum amount of solute that
can be dissolved in a given amount of solvent to form a homogenous
system at specified temperature’’.
o The solubility of drug is represented through various
concentration expressions such as parts, percentage, molarity,
volume fraction, mole fraction.
FACTOR AFFECTING SOLUBLIZATION:
Particle size
Temperature
Pressure
Molecular size
Nature of solute
Polarity
Polymorphs
NEED FOR SOLUBILITY ENHANCEMENT:
There are variety of new drug and their derivatives are available but
less than 40% of lipophilic drugs candidates fail to reach market due
to poor bio-availability.
The lipophilic drug that reach market requires a high dose to attain
proper pharmacology action.
SOLUBILITY OF DRUG OCCUR DUE TO:
o Polarity of solvents, A polar solvent dissolves ionic solutes and
other polar substances.
o The ability of solute to form hydrogen bond with solvent.
o Also depends on the ratio of the polar to non-polar group of the
molecule.
TECHNIQUES FOR SOLUBILITY ENHANCEMENT:
Various techniques have been using to attempt to improve solubility
and dissolution rates of poorly water-soluble drugs which includes as
followings:
1) Particle Size Reduction
Conventional methods
Micronization
Nanosuspension
2) Hydrotropy
3) Co-solvencyz
4) Solubilization by surfactants
5) Solid dispersion
The fusion (Hot melt) method
The solvent (evaporating) method
Dropping (Hot melt extrusion) method
6) pH adjustment
7) High pressure homogenization
8) Superficial fluid recrystallization
9) Sonocrystalization
10) Complexation
Physical mixture
Kneading method
Co-precipitate
11)Spray Drying
12) Inclusion complex Formation-Based technique
13)Liquisolid technique
14)Micro-emulsion
15)Self-emulsifying drug delivery System
16)Neutralization
17)Cryogenic method
Spray freezing onto cryogenic fluids
Spray freezing into cryogenic liquids (SFL)
Spray freezing into vapor over liquid (SFV/L)
Ultra-rapid freezing (URF)
18)Polymeric alteration
19)Salt formation
II) Nanosuspension
The technology is applied to poorly soluble drugs that are
insoluble in both water and oils.
A pharmaceutical nanosuspension is biphasic system
consisting of nano sized drug particles stabilized by
surfactants for either oral and topical use or parenteral and
pulmonary administration.
The particle size distribution of the solid particles in
nanosuspension is usually less than one micron with an
average particle size ranging between 200 and 600 nm.
2) Hydrotropy
3) CO-SOLVENCY
o The solubility of poorly soluble drugs in water can be
increased by mixing it with some water miscible solvent in
which the drug is rapidly soluble. This process is known as
co-solvency and the solvent use known as co-solvent.
o Co-solvent system works by reducing the interfacial
tension between the aqueous solution and hydrophobic
solute. It is also commonly referred to as solvent
blending.
o Co-Solvency is one of the most popular approaches for
improving the solubility of poorly aqueous soluble drugs
in pharmaceutical liquid formulations. Cosolvents have
hydrogen bond donor and/or acceptor groups as well as
small hydrocarbon regions.
o Hydrophobic hydrocarbon regions interfere with waters
hydrogen bonding network, reducing the overall
intermolecular attraction of water. Consequently, reduces
the intermolecular attraction of water while the hydrogen
bond ensures water solubility.
4) SOLUBLIZATION BY SURFACTANT:
5) SOLID DISPERSION:
o Solid dispersion as group of solid products consisting of at
least two different component, generally hydrophilic and
hydrophobic drug.
o The term solid dispersion refers to a group of solid products
consisting of at least two different components, generally a
hydrophilic matrix and a hydrophobic drug.
o The most commonly used hydrophilic carriers for solid
dispersions include polyvinylpyrrolidone (Povidone, PVP),
polyethylene glycols (PEGs), Plasdone-S630. Surfactants like
Tween-80, docusate sodium, Myrj-52, Pluronic-F68, and
sodium lauryl sulphate (SLS) also find a place in the
formulation of solid dispersion.
a) The fusion (melt) method:
c) Dropping method:
A solid of a melted drug-carrier mixture is pi petted and
then dropped onto a plate, where it solidifies into round
particles.
The size and shape of the particles can be influenced by
factors such as the viscosity of the melt and the size of the
pipette. Because viscosity is highly temperature
dependent, it is very important to adjust the temperature
so that when the melt is dropped onto the plate it solidifies
to a spherical shape.
6) pH ADJUSTMENT:
9) SONOCRYSTALISATION
o The novel approach for particle size reduction on the basis of
crystallization by using ultrasound is son crystallisation.
o Son crystallisation utilizes ultrasound power characterized by
frequency range of 20-100kHz for including crystallization.
o It is not only enhancing the nucleation rate but also an effective
means of size reduction and controlling size distribution of the
active pharmaceutical ingredients.
o Most applications use ultrasound in the range 20 kHz-5 MHz.
10)COMPLEXATION
o Complexation of drugs with cyclodextrins has been enhance
aqueous solubility and drug stability.
o Cyclodextrins of pharmaceutical relevance contain 6, 7 or 8
dextrose molecules bound in a 1, 4 configuration to form ring of
various diameters.
o The ring has a hydrophilic exterior and lipophilic core in which
approximately sized organic molecules can form noncovalent
inclusion complexes resulting in increased aqueous solubility
and chemical stability.
o Complexation relies on relatively weak forces such as London
forces, hydrogen bonding and hydrophobic interaction.
TECHNIQUE OF COMPLEXATION
1. Physical mixture:
Active drug with suitable polymer in different ratios mixed in a
mortar for about one hour with constant trituration.
The maximum is passed through sieve no.80 and stored in
desiccator over fused calcium chloride.
2. Kneading method:
active drug with suitable polymer in different ratios is added to
the mortar and triturated with small quantity of ethanol to
prepare a slurry
slowly the drug is incorporated into slurry with constant
trituration the prepared slurry rate is then air dried at 250 degree
for 24 hours.
The resulting product is pulverized and passed through sieve
no.80 and stored in desiccator over fused calcium chloride.
3.Co-precipitate method:
o Active drug is dissolved in ethanol at room temperature and
suitable polymer is dissolved in distilled water.
o Different molar ratios of active drug and suitable polymers are
mixed respectively.
o The mixture is stirred at room temperature for 1 hour and the
solvent is evaporated the resultant mass is pulverized.
o And pass through sieve number 80 and stored in a desiccator
11) SPRAY DRYING:
o The solvent evaporation of drug and polymer solution in
different ratio is carried out by using spray dryer
o the solutions are prepared by dissolving drug in methanol and
polymer in distilled water and mixed both solution which
produces a clear solution.
o The solvent evaporated by using evaporator.
o The spray dried mixture of drug with polymer is obtained in 20
to 30 minutes.
12) INCLUSION COMPLEX FORMATION-BASED
TECHNIQUE:
o inclusions complexes are formed by the insertion of the non-
polar molecules or the non-polar region of one molecule (known
as guest) into the cavity of another molecule or group of
molecules (known as host). EXA-cyclodextrin
o the cavity of host must be large enough to accommodate the
guest and small enough to eliminate water so that the total
contact between the water and the non-polar regions of the host
and the guest is reduced.
TECHNIQUES OF INCLUSION COMPLEX METHOD:
i. Lyophilization or a freeze-drying technique:
In order to get a porous amorphous powder with a high degree
of interaction between drug and CD.
in this technique the solvent substance from the solution is
eliminated a primary freezing and subsequent drying of the
solution containing both drug and CD at reduced pressure.
Thermolabile substances can be successfully made into complex
form by this method.
Limitations
Use of specialized equipment.
Time consuming process.
Poor flowing powder product.
13)LIQUISOLID TECHNIQUE:
16) NEURARRALIZATION: