This document discusses various techniques for improving the solubility of poorly soluble drugs, including physical modifications like polymorphism, amorphization, solid dispersions, and lyophilization. It also covers chemical modifications such as changing pH, complexation, salt formation, and prodrug strategies. Additional methods involve using surfactants, cosolvents, or hydrotrophic agents. The document provides examples for each technique and explains their mechanisms for enhancing aqueous solubility and bioavailability. In summary, it provides an overview of important solubilization techniques and how they can be applied to formulate drugs with poor water solubility.

1. SOLUBILIZATION & TECHNIQUES
OF SOLUBILIZATION
Prepared by:
Gohil Riyaz
M.Pharm 1st year
Dept.of pharmaceutics

2. CONTENTS
 Introduction
 Important of Solubility
 Techniques of solubilization
a)Physical modification
b)Chemical modification
c)Micelleneous methods
 Reference

3. INTRODUCTION
 SOLUBILITY: Solubility is defined in quantitative
terms as concentration of solute in concentrated solution
at a certain temperature, and in qualitative way it can be
defined as a spontaneous interaction of two or more
substance to form a homogeneous molecular dispersion.
 SOLUBILIZATION: Solubilization can be defined as a
preparation of thermodynamically stable isotropic
solution of a substance normally insoluble or slightly
soluble in a given solvent by introduction of an
additional component or components.

4. The pharmacopoeia lists solubility in terms of number of millilitres
of solvent required to dissolve 1g of solute. The Indian
pharmacopoeia provides general terms to describe a given range.
The descriptive term are given as:
DEFINATION PARTS OF SOLVENT
REQUIRED FOR 1 PART OF
SOLUBILITY
Very soluble <1
Freely soluble 1-10
Soluble 10-30
Sparingly soluble 30-100
Slightly soluble 100-1000
Very slightly soluble 1000-10000
Insoluble >10000

5. IMPORTANCE OF SOLUBILITY
 Therapeutics effectiveness of a drug depends upon the
bioavailability and ultimately upon the solubility of drug
molecule.
 It is important parameter to achieve desired
concentration of drug in systemic circulation for
pharmacological response to be shown.
 Any drug to be absorbed must be soluble or present in
the form of an aqueous solution at the site of
absorption.

6. TECHNIQUES OF SOLUBILIZATION
A) Physical modification:
a) Crystal habit modification:
1)Polymorphs
2)Amorphous
3)Pseudopolymorps
b) Drug dispersion:
1)Eutectic mixture
2)Solid dispersion
3)Solid solution
c) Lyophilisation:

7. a) Crystal habit modification:
1) Polymorphs:
Polymorphs exist in a) stable form
b) metastable form
a) Stable form- shows low aqueous solublity
b) Metastable form-shows high aqueous
solublity
e.g: The polymorphic form III of riboflavin is
20 times more water soluble than the form I

8. 2) Amorphous:
They have greater aqueous solubility than the
crystalline form because the energy required to
transfer e molecule from crystal lattice is
greater than that required for amorphous solid.
e.g: Amorphous form of Novobiocin is 10 times
more soluble than the crystalline form

9. 3) Pseudopolymorphism(Hydrates & Solvates):
The anhydrous form of drug has greater
aqueous solubility than the hydrates, because
of the hydrates are already in interaction with
water and therefore have less energy for
crystal breakup in comparison to the
anhydrous for further interaction with water.
e.g: Anhydrous form of theophylline have higher
solubility in comparison to their monohydrate
form.
The organic solvates have greater aqueous
solubility than non solvates.
e.g: Chloroform solvates of griseofulvin more
water soluble than their non solvate form.

10. b) Drug dispersion:
1) Eutectic mixture:
When the eutectic mixtue is exposed to water
the soluble carrier dissolves leaving the drug in
a microcrystalline state which solubilize
rapidly.
e.g: Mixture of paracetamol
and urea.

11. 2) Solid dispersion:
Prepared by solvent or co precipitation method.
In it guest solute + solid carrier solvent
Dissolved in a common volatile liquid solvent
such as alcohol.
The liquid solvent is removed by evaporation
under reduced pressure or by freeze drying
which results in amorphous precipitation of
guest in crystalline carrier which solubilizes
rapidly.
e.g: Amorphous sulfathiazole in crystalline urea.

12. 3) Solid-solution:
Two components crystallise together in a
homogeneous one phase system, because of
reduction in particle size to the molecular level
solid solution shows greater aqueous solubility.
e.g: Griseofulvin from such solid solution
dissolves 6 to 7 times faster than pure
griseofulvin

13. c) Lyophilisation:
Amorphous powder with high degree of
interaction between drug and carrier like
cyclodextrine it get in to porous—
solubilized rapidly.
e.g: Indomethacin having low solubility in water--
--- increased by lyophilisation.

14. b) Chemical modification:
1) Change of pH
2) Complexation
3) Salt formation
4) Prodrug

15. 1) Change of pH:
This can be achieved in two ways
a) In situ salt formation
b) Addition of buffers to formulation.
e.g: Buffered aspirin tablet.

16. 2) Complexation:
The beta and gamma cyclodextrin having
ability to form molecular inclusion
complexes with hydrophilic drug having
poor aqueous solubility.
Cyclodextrin are versatile in having
hydrophobic cavity of suitable enough to
accomodate the lipophilic relatively
hydrophilic ---- improved aqueous solubility
e.g: Barbiturates, Benzodiazepines.

17. 3) Salt formation:
Salts have improved solubility in comparison to
the original drug.
e.g: Alkali metal salts of acidic drugs like
penicillin and strong acid salt of basic drugs like
atropin are water soluble than parent drugs.

18. 4) Prodrug :
Solubility can be increased by conversion of
drug into prodrug.
e.g: Chloroform and Tocopherols are poorly
aqueous soluble drugs, solubility increased by
succinate ester prodrug of chloromphenicol and
tocopherols.

19. c) Micellenious methos:
1) Use of surfectant
2) Cosolvency
3) Hydrotrophic agent

20. 1) Use of surfactant:
Surfactant reduced the interfecial tension.
Enhance solubility by promoting wetting and
penetration of dissolution fluid into the solid
drug particles.
e.g: Spironolactone(steroids)--- increased
solubility by using surfactant(non ionic
polysorbates).

21. 2) Cosolvency:
The polar water environment more non polar
like the solute- cosolvents facilitates
solubilization.
e.g: PEG400 is improving the solubility of
hydrochlorthiazide.

22. 3) Hydrotrophic agent:
Hydrotrophy desigate the increase in solubility
in water due to th presence of large amount of
additives.
The mechanism related to complextion
involving a weak interaction the hydrotrophic
agent and solute.
e.g: Solubilization of theophylline with sodium
acetate and sodium alginate.

23. REFERENCE
 Text book of biopharmaceutics and
pharmacokinetics by brahmankar, page
no.349-366

24. THANK YOU