Three sentence summary: Solid dispersion techniques can be used to improve the solubility and bioavailability of poorly soluble drugs. Various methods can be used to prepare solid dispersions, including solvent evaporation, melting, and spray drying. Characterization of the solid dispersions is important and can be done using methods like thermal analysis, spectroscopy, and dissolution testing to understand the physical properties and drug release behavior.

1. Solubility of poorly soluble drugs by using solid dispersion
technique
Presented by
Mr.Jagadeesh
tekkali
B.Pharmacy
11AC1R0076
VIGNAN INSTITUTE OF PHARMACEUTICAL TECHNOLOGY,DUVVADA

2. Introduction:
poorly soluble drugs like glibenclamide is an ant diabetic drug under the canary
of sulphanyl urea 2.genration with is act by the potassium sensitive ATP channel by regulate
insulin release from b-cell of pancreas glibenclamide is a potent drug having longer biological
half life such as 10hours. So it leads toxicity to body blood. In order to seed bioacgical half
improve the solubillty increase the biciavllabillty which is safest drug during pregnancy. Which
class it drug Pearly water soluble drug under BCS class2 drug that means’ high permeability low
solubility.
Increase bioavailability of poor water soluble drugs e.g.: bcs class 2 drugs like
glibenclamide/glyburide by using SD methods. Recent development in novel drug delivery
systems such as SD technology. In that solid product consisting of at least two different components
generally a hydrophobic drug can be incorporated into hydrophilic drug carrier. To form a SD (solid
dispersion) by using different technique. Carrier should be crystalline or
amorphous.

3. Which is the simplest, advantageous oral bioavailability of a drug depends on it solubility and dissolution
of drugs therefore efforts to increase dissolution of drugs.
In formulation of poorly soluble drugs some hydrophilic carriers and super disintegrating agents such as
PEG 2000,4000,6000. Etc and sodium starch glycolate(premesol), cross linked sodium CMC
HPMC.added to enhance the disintegration and their by abosorption and bioavailability. In a SD
technology and NDDS aims to improve safety and formulated into convential dosage forms increase
patient compliance.
These dosage forms dissolve or disintegrate rapidly in the oral cavity with
in a matter of seconds without the need of water.SD method dissolution can be improved by
increase the surface area and thereby reducing the particle size.

4. Types of solid dispersions:
 Simple eutectic mixtures
 Solid solutions
 Glass solutions
 Amorphous precipitation in a crystalline carrier
Simple eutectic mixtures: when a solution/mixture contain two components such as A,B which
is placed in solution “S”.solution can be rapid cooling then A,B components such are crystalline
out to form very fine crystals when a mixture with composition”S”. Poorly soluble drug and inert
water soluble carrier (PEG, PPO, and PEO).so carrier contact with aqueous media and larger
surface area resulting more dissolution rate and improved bioavailability.
carrier Drug carrier Solid dispersion drug .
Solid solutions: in a solid solution the two components crystallize together in homogeneous mono phasic system. The
particle size of drug in the solid solution is reduced to it molecular size. So which achieve faster dissolutions rate?
Which is classified into two?
Continuous solid solutions
Discontinuous solid solutions
Classification of solid dispersion systems

5. Continuous solid solutions: in a mixture/solution contain two components are
formed/completed miscible with each to form solid mass.intraction B/W two components are
more grater then individual components.
Discontinuous solid solutions: in a mixture contain two components are limited miscibility or
partially with each other to form solid mass. In that interactions B/W two components are lower
than individual components atom interactions indusial components atom interactions .due to
higher interactions individual components equal paten of solubility until critical temperature
reached.
Glass solutions and suspensions: a glass solution is a homogenous; glass system in which a
solute dissolves in glass solvents .glass solvents is a pure chemical or a mixture of chemical in a
glassy. The glassy is usually obtained by an abrupt quenching of the melt. It is characterized by
transparency and on heating, brittleness below the “glass transition temperature” (Tg) on heating,
it soften progressively and continuously without a sharp melting point.
Amorphous solid solution: in that polymer carriers are particularly likely to form amorphous
solid solutions as other polymer itself often present in the form of an amorphous polymer chain
network in the in additions, the solute molecules may serve to plasticize the polymer, leading to a
reduction in its glass transition temperatur

6. Selection of carriers: the selection of hydrophilic carriers. Should have some ideal qualities
such as
Readily soluble in water and GI fluids
Physiological inert
Melting point not much higher than of the drug
Relatively low vapor pressure
They should be non toxic
“Carrier/matrix is melted at elevated temperature and the drug is dissolved. In molten carriers
.surface active agents are substance at low concentration adsorb on to the surface.
First generation carriers
Example: Crystalline carriers: Urea, Sugars, and and Organic acids
Second generation carriers
Example: Fully synthetic polymers include providence (PVP),
polyethylene glycols (PEG) and polymethacrylates. Natural product based polymers
are mainly composed be cellulose derivatives, such as
hydroxypropylmethylcellulose(HPMC), hydroxypropylcellulose or starch derivates, like
cyclodextrins.
Third generation carriers
Example: Surface active self emulsifying carriers:Poloxamer 408,Tween80, and Gelucire 44/14[12]
carrier
Carrier(hydrophilic) Substances/drugs(hydrophobic), PEG Griseofulvin, PVP Flufenamic acid,HPMC
Albendazole,benipine ,Poloxamer188 Enteric polymer aspirin ,Urea Ofloxacin Sorbitol Predinisolon
Types of carrier

7. Advantages of solid dispersion techniques:
 Particles with reduced particle size: molecular dispersions as a solid dispersion and
represent the last state on particle size reduction and after inert carrier drug incorporated
into it their by increase the surface area in order to increase dissolution rate and
bioavailability.
 Particles with higher porosity: particles in solid dispersion have been found to have a
high degree of porosity and increase in porosity also depending properties of carrier
molecules. If polymer having linear structure is utilized more pare in solid dispersion. So
high dissolution rate.
 Particles with improved wet ability: if solid dispersion carrier which is hydrophilic so
more aqueous content their by more wet ability and improve the dissolutions
Drug in amorphous state: if a drug poorly water soluble crystalline drugs when in the
amorphous state tend to have higher degree of solubility drug in its amorphous state shows
higher drug release because no energy is required to break up the crystal lattice during thedissolution
process.
 Metastable Forms Formation of metastable dispersions with reduced lattice energy
would result in faster dissolution rates. It was found that the activation energies for
dissolution for furosemide was 17 K Cal per mol, whereas that for 1:2 furosemide: PVP
co precipitate was only 7.3 K Cal per mol.
To obtain a homogeneous distribution of a small amount of drug in solid state.)To stabilize the unstable
drugs.
 To dispense liquid or gaseous compounds in a solid dosage.
To formulate a fast release primary dose in a sustained release dosage form

8. Disadvantages of Solid Dispersion
The major disadvantages of solid dispersion are related to their instability. Several systems
have shown changes in crystallinity and a decrease in dissolution rate with aging. The
crystallization of ritonavir from the supersaturated solution in a solid dispersion system was
responsible for the withdrawal of the ritonavir capsule (Norvir, Abboft) from the
market.Moisture and temperature have more of a deteriorating effect on solid
dispersions than onphysical mixtures. Some solid dispersion may not lend them to easy
handling because of tackiness

9. CHARACTERIZATION OF SOLID DISPERSION
Many methods are available that can contribute information regarding the physical
nature of solid dispersion system. A combination of two or more methods is
required to study its
•Thermal analysis.
•Spectroscopic method.
•X-ray diffraction method.
•Dissolution rate method.
•Microscopic method.
•Thermodynamic method.
•Modulated temperature differential scanning calorimetry
•Environmental scanning electron microscopy
•Dissolution testing.

10. Method of preparation of solid dispersion:
a. Kneading technique: in this method carrier is permeated with water and transformed to
paste drug is then added and kneaded for particular time. The kneaded mixture is then
dried and passed. Through sieve if necessary.
b. Solvent evaporation method: in this method both drug and carrier are dissolved in
organic solvent after entire dissolution, the solvent is evaporated. The solid mass is
ground, sieved and dried.
c. Co-precipitation method: required amount of drug is added to the solution of carrier.
The system is kept under magnetic agitation and protected from the light the formed
precipitate is separated by vacuum filtration and dried at room temperature.
d. Melting method/fusion method: drug and carrier are mixed using motor and pestle to
accomplish a homogenous dispersion the mixture is heated at or above the melting point
of all components. It is then cooled to acquire congealed mass. It is crushed and sieved.

11. e. Lyophillization technique: freeze-drying involves transfer of heat and mass to and
form
the product under preparation this technique. Where the drug and carrier are co
dissolved
in a common solvent, frozen. And sublimed to obtain a lyophilized molecular
dispersion.
f. Melt agglomeration process: this technique has been used to prepare SD. Where
the
binder act as a carrier ,drug and recipients are heated to temperature above the melting
point of the binder (melt-in procedure) by spraying a dispersion of drug in molten
binder
on the heated incipient (spray-on-procedure)by using a higher shear mixture.
g. Spray-drying method: drug is dissolved in suitable solvent and the required
amount of
carrier is dissolved in water. Solution is mixed by sonication/other suitable method to
produce a clear solution. Which is then spray dried using spray dryer.
h. Electro spinning method: in this method polymer industry combines solid solution
methods with nana technology. In this procedure a liquid stream of drug/polymer
solution
is subjected to a potential 5 to 30 KV. When electrical force prevail over in the surface
tension of the drug /polymer solution at the air interface, evaporates can be screened

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