1) Solid dispersion is a method to improve the solubility of poorly water soluble drugs by dispersing drugs in a hydrophilic carrier. It involves mixing the drug with a carrier on a molecular or microscopic level. 2) Common methods for preparing solid dispersions include fusion, solvent evaporation, spray drying, and melt extrusion. These methods aim to convert crystalline drugs into amorphous forms within hydrophilic carriers. 3) Characterization techniques like DSC, XRD, and dissolution testing are used to analyze the molecular state of drugs in solid dispersions and evaluate increases in solubility and dissolution rate compared to raw drugs.

1. Prepared by
Ajinkya N. Nikam
(F.Y.M.Pharm, Sem-I)
ajinkya.nikam7@gmail.com
Department of Pharmaceutics
H. R. PATEL INSTITUTE OF PHARMACEUTICAL EDUCATION & RESEARCH
SHIRPUR (M.S.) 425 405
2015 – 2016
Guided by
Dr. P. K. Deshmukh
Head of Department
ENHANCEMENT OF SOLUBILITY BY SOLID DISPERSION

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Sr. No. Content Slide no.
1 Introduction 3
2 What is Solubility? 4
3 Solid Dispersion 5
4 Need of Solid Dispersion 6
5 Solid Dispersion Methods 7
6 Characterization of Solid Dispersion 17
7 Advantages 18
8 Disadvantages 19
9 Application 20
10 Marketed Formulations 21
11 Summary 22
12 Conclusion 23
13 References 24,25,26
14 Trivia 27
15 Acknowledgment 28
Table of Contents

3. Introduction1
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Therapeutic effectiveness of a drug
depends upon the bioavailability and
ultimately upon the solubility of drug
molecules.
Solubility is one of the important
parameter to achieve desired concentration
of drug in systemic circulation for
pharmacological response to be shown.
Important!
Solid Dispe
Important!
Currently only 8% of new drug
candidates have both high
solubility and permeability.

4. What is Solubity?2,3
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The transfer of molecules or ions from a solid
state into solution is know as dissolution.
The extent (maximum) to which dissolution
proceeds under a given set of experimental
conditions is referred to as the solubility of the
solute in the solvent.
Important!
Quantitatively
Concentration of
Solute
Saturated Solution
Qualitatively
spontaneous interaction
of substances
homogenous molecular
dispersion

5. Solid Dispersion4,16,17
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Enhancement of solubility by Solid Dispersion A.N.Nikam
The term solid dispersions refer to a group of solid products
consisting of at least two different components, generally a
hydrophilic matrix and a hydrophobic drug.
According to Chiou and Rielman (1971) , a pharmaceutical
solid dispersion is ‘the dispersion of one or more active
ingredients in an inert carrier matrix at solid state prepared by
melting (fusion), solvent or melting solvent method’.
Further, Corrigan, 1985, defined solid dispersions as products
formed by converting a drug-carrier combination in fluid state to
the solid state. Hydrophilic polymers are the most used carrier
materials for the preparation of solid dispersions.
Important!
Solid Dispersion= Hydrophobic
Drug + Hydrophilic Matrix

6. Need of Solid dispersion3,4
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Enhancement of solubility by Solid Dispersion A.N.Nikam
In Biopharmaceutical Classification System (BCS) drugs
with low aqueous solubilty and high membrane permeability
are categorized as Class II drugs.
Therefore, Solid Dispersion technologies are particularly
promising for improving the oral absorption and
bioavailabilty of Class II Drugs.
Important!
Now a days More than 40%
drugs are lipophilic & having a
problem of poor water solubility.

7. Solid Dispersion Methods4-11
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F u s i o n M e t h o d
M e l t E x t r u s i o n
S o l v e n t E v a p o r a t i o n
Ly o p h i l i z a t i o n
S p r a y D r y i n g

8. Fusion Method6
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Fusion or Melting method was first introduced by Sekiguchi
et al. in 1961 where the drug was melted in a carrier and after
cooling the dry mass obtained was pulverized and sieved to
obtain powder.
They prepared the SDs of Sulfathiazole in different carriers
(e.g. ascorbic acid, acetamide, nicotinamide, nicotinic acid,
succinimide and urea) by the formation of melt of different
drug carrier mixtures.
Cooling of the drug-carrier melt was done on ice bath with
continuous stirring until the dry mass was obtained.
Important!
Method developed by
Sekiguchi et al. in 1961 was the
first one among the SOLID
DISPERSION range.

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Hot Melt Extrusion is essentially same as the fusion
method except that intense mixing of component is
induced by extruder.
However, compared to the traditional fusion
method, this technique offers the possibility of
continuous production, which makes it suitable for
large scale production.
Furthermore, the product is easier to handle at the
outlet of the extruder the shape can be adapted to
the next processing step without grinding.
Figure 1: The leistritz twin screw extruder
Hot Melt Extrusion Technology 4,6,7
Important!
Thermo-sensitive drugs &
carrier would not be used in this
technique as they will be
subjected to degradation

10. Fig 2. Diagramatic representation of Hot Melt Extrusion technique
Homogeneous mixture of active, polymer
plasticizer, surfactant
Hot Melt Extrusion Technique
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Enhancement of solubility by Solid Dispersion A.N.Nikam

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Hot Melt Extrusion Technology

12. Solvent Evaporation Method8
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In this Method of Solvent Evaporation, the drug and carrier
are dissolved in common solvent, and then the solvent is
evaporated under vacuum to produce a solid.
Example, solid solution of the highly lipophilic β-carotene
in the highly water soluble carrier povidone.
Important!
Tachibana and Nakamura were
the first to dissolve both the
drug and the carrier in a
common solvent and then
evaporate the solvent under
vacuum to produce a solid.
DRUG + CARRIER
Same Solvent
Evaporation
Under Vacuum
Solid Remains

13. Lyophilization Technique9,10
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Lyophilization has been thought of a molecular mixing
technique where the drug and carrier are co dissolved in a
common solvent, frozen and sublimed to obtain a
lyophilized molecular dispersion.
This technique was proposed as an alternative method to
solvent evaporation.
Its applicable for the thermolabile or otherwise product
unstable in aqueous solutions for prolonged storage
periods, but that are stable in the dry state.
Sublimation of water can take place at pressures and
temperature below triple point
Important!
TRIPLE POINT?
The temperature and pressure at
which 3 phases (Gas, Solid,
Liquid) of substance coexist in
thermodynamic equilibrium.

14. Lyophilization Cycle
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Sample
Preparation Freezing
Primary
Drying
Secondary
Drying
Final
Product
Annealing
Fig 3. Lyophilization Cycle

15. Spray Drying5,11
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Figure 4: An illustration of a spray drying technique
Spray drying is an efficient technology for solid
dispersion manufacturing since it allows extreme rapid
solvent evaporation leading to fast transformation of an
API-carrier solution to solid API-carrier particles.
Important!
The first use of drying of
products from an atomized
liquid stream was already done
by Percy in 1872 (Percy, 1872).
And he got patent for the same.

16. Spray Drying Technique
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17. Characterization of solid dispersions12,13
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Several techniques have been available to investigate the molecular arrangement in solid
dispersions.
However, most effort has been put in to differentiate between amorphous and crystalline
material.
Various methods include,
 DSC
 Powder X-ray diffraction method (Sharper diffraction peaks = crystalline material.)
 Spectroscopic methods (FTIR)
 Microscopic method (Hot-stage microscopy) and
 In-vitro dissolution studies.

18. ADVANTAGES OF SOLID DISPERSIONS14
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Generally, solid dispersion is mainly used
1. To reduced particle size.
2. To improve wettability.
3. To improve porosity of drug.
4. To decrease the crystalline structure of drug in to amorphous form.
5. To improve dissolvability in water of a poorly water-soluble drug in a
pharmaceutical.

19. Disadvantages14
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Laborious and expensive method of preparation.
Reproducibility of physical characteristics.
Difficulty in incorporating into formulation of dosage
form.
Stability of drug and vehicle.
Important!
Phase seperation can be
prevented by maintaining a low
molecular mobility of matrix &
drug during preparation.

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To increase the solubility of poorly soluble drugs thereby
enhance the dissolution rate, absorption and
bioavailability.
To obtain a homogeneous distribution of a small amount
of drug in solid state.
To increase bioavailability of drugs.
Pharmaceutical Applications of Solid dispersion4,15
Important!
In spite of almost several year
of research on solid dispersion,
their commercial applications
are limited. Only Few products
are being marketed so far.

21. Marketed Products4
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Sr.
No
Brand Name Manufacturer API Carrier
1 Gris-PEG Novartis Griseofulvin PEG*
2 Cisamet Lily Nabilone PVP**
3 Sporanox Janseen Pharmaceutica Itraconazole PEG 20.000,
HPMC***
*PEG - Polyethylene gycol
**PVP - Polyvinylpyrrolidone
***HPMC - Hydroxypropyl Methylcellulose

22. Summary
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
What is Solubility?

Solid Dispersion
 Need of Solid Dispersion

Solid Dispersion Methods

Characterization of Solid Dispersion

Advantages& Disadvantages

Application

Marketed Formulations

23. Conclusion
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Solid Dispersion is a best method to deliver a lipophilic drug by oral route.
Solubility enhancement of poorly water soluble drugs remains one of most
challenging aspects of drug development.
The solid dispersion method is one of the effective approaches to achieve the goal
of solubility enhancement of poorly water soluble drugs.
Various techniques, are successfully used for the preparation of solid dispersions in
the lab scale and can be used at industrial scale also.

24. References
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1. James K; “Solubility and related properties”, vol. 28, Marcel Dekker, Newyork, 986, pp.127 –146, 355 – 395.
2. PHARMACEUTICS: The Science of Dosage Form Design, Edited by M. E. Aulton, 2nd Edition, Churchill Livingstone
Publication, Elsevier Limited, Page No. 16.
3. Kumar B. P., Ramanamurthy K. V., Sahu R.K., “Journal of Chemical and Pharmaceutical Science”, Vol. 4 Issue 4, October2011,
Pages170-179
4. Dhirendra K, Lewis S, Udupa n, Atin N, “Solid dispersions-a review” - Pak J Pharm Sci Vol 22(2) (2009 Apr) , 234-246
5. Paudel, A., et al., Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: Formulation and process
considerations. Int J Pharmaceut (2012), http://dx.doi.org/10.1016/j.ijpharm.2012.07.015
6. Jishnu Vijay et al., A basic insight into the stability and manufacturing aspects of solid dispersions, Vol. 3 | Issue 2 | Apr-Jun 2012,
IP: 64.233.173.174]
7. www.youtube.com/watch?V=uIIMmyIiF70 (cited on 2.05.2015)
8. Ketan T. Savjani, et al, Drug Solubility: Importance and Enhancement Techniques, ISRN Pharmaceutics,Volume 2012, Article ID
195727, doi:10.5402/2012/195727

25. Refereces contd..
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9. Ladan Akbarpour Nikghalb et al, Solid Dispersion: Methods and Polymers to increase the solubility of poorly soluble
drugs, Journal of Applied Pharmaceutical Science Vol. 2 (10), pp. 170-175, October, 2012, DOI:
10.7324/JAPS.2012.21031, ISSN 2231-3354.
10. GR.Nireesha et al. Lyophilization/Freeze Drying - An Review, INTERNATIONAL JOURNAL OF NOVEL TRENDS IN
PHARMACEUTICAL SCIENCES, VOLUME 3 | NUMBER 4 | OCT | 2013 ,ISSN: 2277 – 2782
11. www.youtube.com/watch?v=Oo4ZCjHnaRw (cited on 4.10.2015)
12. Iswarya Sridhar, et al,“Solid Dispersions: an Approach to Enhance Solubility of poorly Water Soluble Drug”Journal of
Scientific and Innovative Research 2013; 2 (3): 685-694
13. Singh et al., A review on solid dispersion, Int. J. of Pharm. & Life Sci. (IJPLS), Vol. 2, Issue 9: Sep.: 2011, 1078-1095,
ISSN: 0976-7126
14. Mogal S et al., Solid dispersion technique for improving solubility of some poorly soluble drugs,Der Pharmacia Lettre,
2012, 4 (5):1574-1586
15. Kalia A., Poddar M., “International Journal of Pharmacy and Pharmaceutical science” 2011, Vol.3, Issue 4.

26. References contd..
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16. Chiou W.L. et al., Pharmaceutical applications of solid dispersion systems, Vol 60, issue 9, september
1971.
17. Corrigan et al., mechanism of dissolution of fast release solid dispersions, Vol 11, issue2-3, Oct 20, 1985

27. Trivia..
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 What is Solid Dispersion?
1. Lipophilic drug + Lipophilic Carrier
2. Lipophilic drug + Hydrophilic Carrier
3. Hydrophilic drug + Lipophilic carrier
4. Hydrophilic drug + Hydrophilic carrier
Is it possible for thermosensitive drug to
prepare SD by Solvent Evaporation
Method?
1. YES
2. NO
•Which method you’ll choose to select the carrier for
particular drug?
1. DSC and FT-IR
2. UV
3. XRD
4. NMR

28. Acknowledgment
I am very grateful to Dr. P.K.Deshmukh Sir for their invaluable
guidance.
I am also thankful to Mr.Abhijeet Pandey, Mr.Swapnil Patil,
Mr.Ramesh Chitalkar, Mr.Kunal Bacchao, Ms.Prachiti Patil,
Ms.Neha Chalase, Ms.Diksha Pagare for their kind help.
My Colleagues provided me direct and indirect help, I am also
thankful to them.
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