Dissolution Enhancement of drugs. Technologies and Effect of Carries

1. Dissolution Enhancement of drugs.
Technologies and Effect of Carries
Presented by
Merajun Alam(568)
Most.Sonia khatun (559)
Apu Marma (566)
Rahana Akter Runa (571)
Ferdows Ahmed (570)

2. Content
Introduction
Factor Affecting Drug Dissolution Rate
Dissolution Enhancement Techniques
Carriers for Dissolution Enhancement
Conclusion

3. Introduction
Dissolution is the process by which a
solid substance goes into solution.
The dissolution rate is a measure of the
actual release rate of the compound at
the given particle size etc. in an aqueous
media.
In the process of absorption of drug
from oral route , dissolution is the rate
limiting step for lipophilic drug .
So , it is necessary to enhance
dissolution of these drug to ensure
maximum therapeutic utility of this drug.

4. Factor Affecting Drug Dissolution Rate
• The dissolution rate of a drug is directly proportional to it’s solubility. So
solubility of a drug substance is a major factor that determine it’s dissolution rate.
• The other factors of drug that affect drug dissolution rate includes
※Solubility
※Particle size
※Polymorphism
※Salt form of drug
※Complexation
※Wettability
※All these factors can be targeted to enhance dissolution of poorly water soluble
drug.

5. Dissolution Enhancement Techniques
Several techniques are used for enhancing dissolution rate .
These techniques are carefully selected on the basis of properties of
drug , excipients and dosage form.
Use of water soluble excipients are common and simplest way to
enhance dissolution rate of hydrophobic drug.
The other techniques that used to enhance dissolution rate are-
 Solid Dispersion
 Inclusion complexation
 Steam aided granulation

6.  Congratulation
 Lipid based formulation
 Melt granulation
 Direct compaction
 Solvent evaporation by ultra rapid freezing
 Co-evaporation
 Interactive mixing
 Adsorption of drug onto high surface area carriers
 Liquid solid compact.
 Solvent deposition

7. Solid Dispersion
• Dispersion of one or more active ingredient in an inert carrier or matrix
at solid state prepared by the melting , solvent or melting- solvent
method.
• Solid dispersion technique improves the solubility dissolution rate and
as a result the bioavailability of poorly water soluble drug is increased.

8. Inclusion complexation
Most widely used method to enhance water solubility and increase
stability of hydrophobic drug.
Most commonly used host molecules are the cyclodextrins.
The complex can be prepared by-
Kneading Technique
Coprecipitation
Neutralisation
Co grinding
Spray drying method

10. Steam Aided Granulation
• Steam is used instead of water in wet granulation
• It provides a higher diffusion rate into the powder and most
favourable thermal balance during the drying step.

11. Co-grinding / Co-micronization
Co-grinding of a poorly water-soluble drug with water-soluble polymers
like hydroxypropylen methylcellulose (HPMC), poly vinyl alcohol
(PVA) etc. It is the presence of small amount of water is extremely
effective to improve its apparent solubility with maintenance of drug
crystallinity to some extent . Small particles produced by milling or
micronization have increased surface area and expected to have
enhanced dissolution rate.

12. Lipid-based formulation
• Lipid based delivery system by emulsions, micro-emulsions,
liposomes, microspheres, solid lipid nanoparticles etc.
• Ability to avoid resistance chemical and physical barriers to
oral absorption
• Most successful in enhancing in bioavailability of molecules
that are poorly water soluble, but highly permeable drug
molecules.

13. Melt granulation
• This technique powdered drugs are agglomerated by a meltable binder, which can be
a molten liquid.
• Temperature raised higher than the melting point.
• No drying step in this process
• Less time consuming
• Uses less energy
• Polyethylene glycol used as-
• Molten binder to its complimentary
solution properties
• Low melting point.
• Rapid solidification rate
• Low toxicity and little cost.

14. Direct compaction
⁕In this process hydroxypropyl methylcellulose and drug is blended.
⁕Compressed into slugs and milled into a granular product
⁕Enhanced dissolution rate of poorly water-soluble drugs without use a
solvent of solid dispersion by these method
⁕Low cost in this method.
⁕This process is quicker.
⁕Particularly effective at enhancing the rate of drug dissolution
⁕Maintained polymers particles during drug dissolution.
⁕Drug and polymer particles rapidly disperse.
⁕Separated in the dissolution medium.

15. Solvent evaporation by ultra-rapid freezing
(URF)
• Freezing a drug contained in a polymer solution onto the surface of a
cryogenic substrate with a thermal conductivity (k) between 10 and 20
W/(m K).
• Rapid conductive heat transfer, resulting in high supersaturation and
nucleation rates.
• The URF technology has the potential to create powders with superior
physicochemical properties.
• The rapid freezing of the drug/polymer composition is decisive in
preventing phase separation.
• Recrystallization of the drug is avoided by the inclusion of high glass-
transition temperature polymers such as PVP.

16. Co-evaporatate system
 Weak basic drugs like prochlorperazine maleate contain good
solubility in acidic pH.
 alkaline pH solubility is significantly reduced and when a
conventional formulation containing weak base is given orally
precipitation of poorly soluble free base occurs within formulation in
intestinal fluid.
 Precipitated drug is no longer capable of release from formulation
leading to decrease in bioavailability of drug.

17. Ordered/Interactive Mixing
 Ordered mixing is described as method to prepare ordered units
 Ordered mixing yields nearly the perfect mix and may be obtained in
a number of ways like mechanical means adhesion.
 an ordered mixture includes that the carrier particle

18. Liquid solid Compacts
 Liquid Compacts are compressible powdered forms of liquid
medications.
 The term “liquid solid medication” implies oily liquid drugs and
solutions or suspensions of water insoluble drugs carried in
suitable non-volatile solvent systems.
 Surfactants like tweens are used to improve aqueous solubility of
poorly soluble drugs

19. Solvent Deposition
A solvent deposition system is a solid preparation in which a drug is
dissolved in a solvent like methylene chloride to produce a solution.
Then the carrier is dispersed .At 25-35C temperature and pressure the
solvent is removed by evaporation .The dissolution rate is increased
by ascribed to the reduced particle size of drug deposited

20. Carriers for Dissolution Enhancement
carrier of dissolution Enhancement of poorly soluble drug which are
soluble and dissolved in water at a fast rate that is widely used in
pharmaceutical formulation . Carriers described in the table 1 under
category .

21. Polymers
A substance which has a molecular structure built up completely from a
large number of similar units bonded together .such as : silk ,wool ,DNA
, cellulose and proteins .polymers means polyethylene glycols
hydroxypropyl methylcellulose ,that is used in low concentration lead to
increased the dissolution rate. In higher proportion of polymers that
decreased the dissolution rate .solid dispersion of glyburide were
prepared using PEG 4000 , PEG 6000 and a mixture such as PEG 4000
and PEG 6000.Dissolution studies showed maximum dissolution rate of
drug with PEG 6000 in 30:70 and 20:80 weight ratios and necessary for
low weight fraction of polymer .

22. The drug pvp in 1:4 ratio ,solid dispersion gave highest dissolution
rate of sbout 38 fold that is rapidly high of pure drug .solid
dispersion of flubiprofen in pvp HPMC ,HPC and PEG 6000 in 19:1
and 9:1 ratio of drug that is carrier were prepared by solvent method

23. Table : Polymers and techniques employed for enhancing dissolution of poorly water
soluble drugs
Drug Polymer Technique Mechanism of Dissolution Enhancemen
Glyburide PEG 4000, PEG 6000
and there mixtures
Solid dispersion by
fusion and solvent
method
Increase in surface area and hence surface free
energy resulting in an increase in the dissolution
Gliclazide PEG 4000 and PEG
6000
Solid dispersion by
solvent method
Reduction of particle size resulting in
enhancement of surface area and increase in
drug wettability
Flurbiprofen Polyvinyl
pyrrolidone (PVP),
Hydroxypropyl
methylcellulose
(HPMC),
Hydroxypropyl
cellulose (HPC),
Poly ethylene glycol
(PEG) 6000
Solid dispersion by
solvent method
Particle size reduction, improved wettability of
drug particle by the carriers, solubilizing effect
of carrier and possible conversion of crystalline
drug into amorphous form

24. Superdisintegrants
Dissolution of poorly water soluble drugs can be markedly improved
by use of superdisintegrants
 Sodium starch glycolate.
 Croscarmellose sodium
 Crospovidone
 crosslinked
 Polyvinylpyrrolidone.
 alginic acid etc

25. Superdisintegrants and techniques employed for enhancing
dissolution of poorly water soluble drugs
Drug Superdisintergrent Technique Mechanism of
Dissolution
Enhancement
Naproxen Cross linked
polyvinylepyrrolidon
Drug loading on
the surface of a
carrier
Higher surface
of the carrier and
capillary action
of carrier

26. Nifedipine Croscarmellose
sodium and
crospovidon
Physical mixture Sweelling action
of
croscarmellose
sodium and
capillary action
of crospovidone
Oxazepam Cross-linked
sodium
Ordered mixing Swelling action
of carrier
Furosemide Sodium starch
glycolate
Formation of co-
precipitate by
solvent method`
Capillary action
of carrier.

27. Surfactants
Surfactants are chemicals that may
be completely invisible to us most
of the time but which benefit our
lives in many different ways. They
can be produced from either
synthetic or natural raw materials
and their versatility makes them
key to both the quality of modern
life and many different industries.

28. Drug Surfactant Technique Mechanism of Dissolution
enhancement
Albendazole Poloxamer Solid dispersed by hot melt
method
Surface active property of
the carrier, decreased
crystallinity of the product
Rofecoxib PoloxamersLutrol Solid dispersion by hot melt
method
Micellar solubilization
and/or reduction of activity
coefficient of the drug
through reduction of
hydrophobic interaction(S)
Piroxicam Labrasol Semi-solid dispersion Increase wetting and
micellar solubilization of
the drug
Piroxicam Tween 80 Liquisolid compact Increased wettability and
surface availability of the
drug to the dissolution
medium
Surfactants and techniques employed for enhancing dissolution of poorly
water soluble drugs

29. Conclusion
Dissolution is the most important phenomenon for a drug and poorly
water soluble drug have low dissolution rate.so it is necessary to enhance
the dissolution rate of these drugs. The techniques used for the
dissolution Enhancement utilize inert carrier to improve the
physicochemical properties of the drugs. If the physicochemical
properties can be improved then the rate of dissolution is increased. So it
can be said that by using those mentioned techniques and carriers
dissolution rate can be enhanced of a drug .