Global journal of

Pharmacy & pharmaceutical Science

ISSN:2573-2250

Review Article Glob J Pharmaceu Sci

Volume 3 Issue 2 - July 2017
Copyright © All rights are reserved by Manoj Kumar Sarangi
DOI: 10.19080/GJPPS.2017.03.555608

Solid Dispersion - a Novel Approach for

Enhancement of Bioavailability of Poorly
Soluble Drugs in Oral Drug Delivery System
Singh N and Sarangi Mk*
Sardar Bhagwan Singh Post Graduate Institute of Biomedical Sciences and Research, India
Submission: May 6, 2017; Published: July 11, 2017
*Corresponding author: Manoj Kumar Sarangi, Sardar Bhagwan Singh Post Graduate Institute of Biomedical Sciences and Research, India;
Email:

Abstract

Improving oral bioavailability of drugs those given as solid dosage forms remains a challenge for the formulation scientists due to
solubility problems. The dissolution rate could be the rate-limiting process in the absorption of a drug from a solid dosage form of relatively
insoluble drugs. Therefore increase in dissolution of poorly soluble drugs by solid dispersion technique presents a challenge to the formulation
scientists. Solid dispersion techniques have attracted considerable interest of improving the dissolution rate of highly lipophilic drugs
thereby improving their bioavailability by reducing drug particle size, improving wettability and forming amorphous particles. The term
solid dispersion is dealing with a group of solid products which is consisting of at least two different components, generally a hydrophilic inert
carrier or matrix and a hydrophobic drug. This article reviews historical background of solid dispersion technology, limitations, classification
and various preparation techniques with its advantages and disadvantages. This review also discusses the recent advances in the field of solid
dispersion technology. Based on the existing results and authors’ reflection, this review give rise to reasoning and suggested choices of carrier
or matrix and solid dispersion procedure.

Keywords: Carrier; Dissolution; Matrix; Poorly soluble drug; Solid dispersion; Solubility enhancement

Abbreviations: SMEDDS: Self-Micro Emulsifying Drug Delivery Systems; G: Energy; GI: Gastrointestinal; PVP: Pyrolidone; PEG: Polyethylene
Glycols; HPMC: Hydroxyl Propyl Methyl-Cellulose; HPbCD: Hydroxypropyl-b-Cyclodextrin; NAP: Solubility of Naproxen; AMP: Ampelopsin;
BCD: β-Cyclodextrin; HPBCD: Hydroxyl Propyl-β-Cyclodextrin; SDs: Solid Dispersions; GBM: Glibenclamide; PEG: Polyethylene Glycol;
SDs: Solid Dispersions; KT: ketoconazole; ME: Microemulsion; HPMCAS: Methylcellulose Acetate Succinate; IND: Indomethacin; PEG4000:
Polyethylene Glycol 4000; PVP K30: Polyvinyl Pyrollidone

Introduction
by utilizing several hydrophilic carriers. Such technique impart
It has been estimated that nearly 35-40 % of drugs suffer
a means of reducing particle size to a nearly molecular level,
from poor aqueous solubility and it affects the absorption of
presenting a variety of processing and excipients options which
drug from gastrointestinal tract that leads to high inter and
allow for flaccidity when formulating oral delivery systems of
intra subject variability, poor oral bioavailability, increase in
low water soluble drugs with cost effectiveness and denoting
dose, reduction in therapeutic efficiency and finally failure in
dose reduction [1].
formulation development. Various formulation strategies like
micronization, solubilization, complexation, dendrimers for Solubility and dissolution
drug solubilization, formation of solid solutions/dispersions
The solubility behaviour of a drug is a crucial determinant of
with hydrophilic carriers, self-micro emulsifying drug delivery
its oral bioavailability. There have been always certain drugs, for
systems (SMEDDS). Nanoparticulate approaches, spray drying,
which solubility has conferred a challenge to the development of
pro-drug approaches and salt synthesis had been attempted
a suitable formulation for oral administration. With the recent
for solubility enhancement. An attractive possibility would be
advent of high throughput screening of potential therapeutic
represented by implementing a simple solid dispersion technique
agents, the number of poorly soluble drug moieties has

Glob J Pharmaceu Sci 3(2): GJPPS.MS.ID.555608 (2017) 001

 Global Journal of Pharmacy & Pharmaceutical Sciences

increased suddenly and thus the formulation of poorly soluble I. Physical modifications [6]
compounds for oral delivery now presents one of the most
o Particle size
frequent and greatest challenges to formulation scientists in the
pharmaceutical industry [2]. The free energy (G) is a measure o Micronization
of the energy available to the system to perform work. Its value
o Nanosuspensions
decreases during a continuously occurring process unless and
until an equilibrium position is achieved when no further energy o Modifications of the crystal habit
can be made available, i.e., ΔG=0 at equilibrium [3]. The solution
o Polymorphs
was developed when an equilibrium is established between
un-dissolved and dissolved solute components in a dissolution o Pseudopolymorphs (including solvates)
process is termed as saturated solution. o Complexation/solubilization
The amount of substance that passes into solution in order to o Utilization of surfactants
establish the equilibrium at constant pressure and temperature
and so produced a saturated solution is known as the solubility o Utilization of cyclodextrines
of the Consideration of the modified Noyes-Whitney equation o Dispersion of Drug in a carrier
(1) provides some hints as to how the dissolution rate of even
very poorly soluble compounds might be improved to minimize o Implication of Eutectic mixtures
the limitations to oral bioavailability of substance. o Solid dispersions (non-molecular)
dC/dt = AD (Cs - C)/h o Solid solutions
Where, dC/dt is the rate of dissolution, A is the surface area II. Chemical modifications
available for dissolution, D is the diffusion coefficient of the
compound, Cs is the solubility of the compound in a dissolution o Soluble prodrug approach
medium, C is the concentration of drug present in the medium o Salt formation
at a time t and h is the thickness of the diffusion boundary layer
adjacent to the surface of the dissolving compound [4]. The main Bioavailability is defined as the rate at which the relative
possibilities or improving dissolution according to this analysis amount of an administered dose of a drug reaches to the
are to increase the surface area available for dissolution by systemic circulation from its site of administration (American
decreasing the size of the particles present in the solid compound Pharmaceutical Association, 1972). Various factors that
by optimizing the wetting phenomenon of the compound influence the bioavaibility of the drug includes the gastric
surface, to decrease the boundary layer thickness, to ensure sink emptying rate, physiochemical properties of the drug, drug
conditions for dissolution and, last but not definitely the least, formulation type, enzymes induction/inhibition by other drugs/
to enhance the apparent solubility of the drug molecules under foods, circadian differences, transporters, diseased state, health
physiologically relevant conditions. The absorption of drug from of the gastrointestinal tract etc. As the contents of GI tract are
the gastrointestinal (GI) tract can be limited by several factors aqueous in nature, hence a drug with poor aqueous solubility
with the most important contributors being poor aqueous possesses low saturation solubility which is correlated with
solubility and/or poor membrane permeability of the drug a low dissolution rate, resulting a poor oral bioavailability.
molecule. About 60% of drugs coming directly from synthetic origin have
solubility below 0.1mg/ml [7].
While delivering an active agent orally, it is very much
important that it must dissolve in gastric and/or intestinal fluids Solid dispersion
before it can reach systemic circulation through GI membrane Solid dispersions are one of the most successful strategies
permeability. Hence, a drug with poor aqueous solubility will to improve drug release of poorly soluble drugs. Sekiguchi and
exhibit dissolution rate limited absorption, and a drug with Obi were the first to describe on solid dispersions in 1961. Solid
poor membrane permeability will basically exhibit permeation dispersion is one of the important strategies to tackle dissolution-
rate limited absorption. Thus, two areas of pharmaceutical rate-limited oral absorption of poorly soluble compounds.
research that focus on improving the oral bioavailability of the Formulation of poorly soluble compounds as solid dispersions
active agents include enhancing solubility and dissolution rate might lead to particle size reduction, improved wetting, reduced
of poorly water-soluble drugs and increasing the permeability of agglomeration, changeability in the physical state of the drug
poorly permeable drugs [5]. molecules and possibly a dispersion in the molecular level,
Several Approaches for enhancement of drug dissolution/ according to the physical state of the solid dispersion. The term
bioavailability of poorly soluble drugs solid dispersion refers to a group of solid products consisting of
at least two different components, generally a hydrophilic matrix

How to cite this article: Singh N, Sarangi M. Solid Dispersion - a Novel Approach for Enhancement of Bioavailability of Poorly Soluble Drugs in Oral Drug
002 Delivery System. Glob J Pharmaceu Sci. 2017; 3(2): 555608.DOI: 10.19080/GJPPS.2017.03.555608
 Global Journal of Pharmacy & Pharmaceutical Sciences

and a hydrophobic drug. The matrix can be either crystalline or Second generation: In second generation solid dispersions,
amorphous. The drugs can be dispersed molecularly, either in amorphous carriers are used instead of crystalline carriers,
amorphous particles (clusters) or in crystalline particles. which are usually polymers. These polymers include synthetic
polymers such as poly vinyl pyrolidone (PVP), polyethylene
Solid dispersion
glycols (PEG), ethyl cellulosepolymethacrylates, natural product
Solid dispersions are classified by various ways, on the based polymers such as hydroxylpropylmethyl-cellulose
basis of their solid state structure as well as on the basis (HPMC) and hydroxypropyl cellulose or starch derivatives like
of carrier used. It is relevant to classify various systems of cyclodextrins.
solid dispersion as per as their fast release mechanisms are
Third generation: Recently, it has been observed that
concerned. Riegelman and Chiou classified solid dispersions into
the dissolution profile can be improved further, if the carrier
the following six representative types: Simple eutectic mixtures,
has surface activity or self-emulsifying properties. Therefore,
amorphous precipitations in a crystalline carrier, solid solutions,
third generation solid dispersions were developed. The use
glass solutions and glass suspensions, compound or complex
of surfactant such as inutec SP1, inulin, compritol 888 ATO,
formation, and combinations of the previous five types [8]. Given
gelucire 44/14 and poloxamer 407 as carriers were shown to be
below is classification of solid dispersion on the basis of carrier
effective in originating high polymorphic purity and enhanced in
used and solid structure in Figure 1 & 2 respectively.
vivo bioavailability.

Drug and polymer exhibiting immiscibility in fluid

state
In case a drug and polymer are immiscible in their fluid
state, it is expected that they would not exhibit miscibility on
solidification of the fluid mixture. Hence such systems might be
considered as similar to their corresponding physical mixtures
and any short of enhancement in dissolution performance
may be leading to modification in morphology of drug and/or
polymer due to the physical transformation (i.e., solid to liquid
state and back), enhanced surface area and/or intimate drug -
polymer mixing.

Figure 1: Classification of solid dispersion on the basis of carrier

Drug and polymer exhibiting miscibility in fluid state
used.
If the polymer and drug are miscible in their fluid state, then
the mixture may or may not undergo phase separation during
solidification, thus influencing the structure of solid dispersion.

Eutectic mixtures
Eutectic mixtures were first described as solid dispersions
in 1961 by Sekiguchi & Obi. Eutectic mixtures are formed when
the polymer and drug are miscible in their molten state, but on
cooling, they crystallize just like two distinct components with
negligible miscibility.

Crystalline solid dispersion

A crystalline solid dispersion is developed when the rate of
drug crystallizes from drug-polymer miscible mixture is greater
Figure 2: Classification of solid dispersion on the basis of solid than that of the rate at which drug-polymer fluid mixture
structure. solidifies.

Amorphous solid dispersion

First generation: The first generation solid dispersions can
be developed by using crystalline carriers like urea and sugar, If the drug-polymer fluid mixture is cooled at a rate that
which were the first carriers to be imparted in solid dispersion. does not allow for drug crystallization, then drug is kinetically
They are having the disadvantage of forming crystalline solid trapped in its amorphous or a “solidified-liquid” state. Such
dispersion, which were thermodynamically more stable and types of dispersions have a high risk of potential for conversion
cannot release the drug as quickly as amorphous ones. to a less soluble and more stable crystalline form.

How to cite this article: Singh N, Sarangi M. Solid Dispersion - a Novel Approach for Enhancement of Bioavailability of Poorly Soluble Drugs in Oral Drug
003 Delivery System. Glob J Pharmaceu Sci. 2017; 3(2): 555608.DOI: 10.19080/GJPPS.2017.03.555608
 Global Journal of Pharmacy & Pharmaceutical Sciences

Solid solution drying, slow evaporation of the solvent at low temperature, the
rotary evaporators, freeze drying and spray drying. Many drugs
Solid solution is defined as a solid dispersion which is miscible
and polymers which could not be utilized for the melting method
in its solid as well as fluid state. These solid solutions may be
due to their high melting points could be used for solvent
either of amorphous or crystalline type. In case of amorphous
evaporation method.
solid solutions, since the drug is molecularly dispersed in the
carrier matrix, hence its effective surface area is predominantly Melting method
higher and thus the dissolution rate of that drug is increased.
The melting method includes the melting of a physical
Crystalline solid solution may results when a crystalline drug is
mixture of carrier and drug into the liquid state followed by
trapped within a crystalline polymeric carrier.
cooling until solidification. However, the method is not useful for
o As per as the miscibility of the two components thermolabile drugs and thus incomplete miscibility is observed
is concerned, the solid solutions are either continuous or between the molten carrier and solid drug.
discontinuous type. In continuous solid solutions, the two
Melting solvent method
components are miscible in the solid state in all proportions.
The components that are miscible at extremes of composition The melting solvent method is a combination of the two
but immiscible at intermediate composition are referred to as methods like melting and solvent evaporation method. It is
discontinuous solid solutions. carried out by dissolving the drug in a suitable solvent and
then mixing of the resultant solution with the molten carrier
o As per the criteria of molecular size of the two
followed by cooling into solidification. The advantage of this
components are concerned, the solid solutions are classified
method is that it requires lower temperatures with lesser risk of
as interstitial and substitutional. In the substitutional solid
decomposition of thermo labile drugs.
solution, the solute molecule substitutes the solvent molecule
in the crystal lattice but, in case of interstitial solid solution, Spray drying process
it is obtained when the solute (guest) molecule occupies the
Spray drying is the process where a solution of drug
interstitial space in the solvent (host) lattice.
substance and carrier is evaporated by spraying the solution
Methods of preparation as fine droplets into a chamber under controlled conditions of
heat, humidity and air flow. The medium of drying is mainly
Various methods for preparation of solid dispersion are associated with hot air and the product is thus separated after
given in Figure 3 [9]. completion of drying.

Hot extrusion method

Hot melt extrusion (HME) is a widely used process in plastic,
rubber, and food industry. The process has been implimented
for the preparation of solid dispersion in a single step. In earlier
periods HME is used to prepare solid dispersion to enhance
solubility of poorly water soluble drugs. But now a days, its value
in developing controlled release dosage forms has gained more
attraction. The key advantages of hot-melt extrusion technique
include lower temperature and shorter residence time of the
drug carrier mixture. Basically, the physical mixture of drug
substance along with other ingredient is fed into the heated
barrel of extruder at a controlled rate. As the physical mixture
is supplied through heated screws, it is converted into a fluid
Figure 3: Methods of preparation of solid dispersion. like state, thus allowing an intimate and homogeneous mixing
by the high shear of extruder screws. The die helps in shaping
the melt in the required form such as pellets, granules, tablets,
Solvent evaporation method
sticks, sheets or powder.
The solvent evaporation technique mainly aims at
Supercritical fluid technology
dissolving the drug and carrier simultaneously in a common
solvent, followed by removal of solvent through evaporation. The supercritical fluid endures as a single fluid phase above
Identification of a common solvent for both carrier and drug its critical pressure and temperature. Carbon dioxide is the
can be problematic and a complete solvent removal from the most commonly used supercritical fluid. In SAS or GAS process
product can be a lengthy process. The solvent can be removed a mixture of drug and polymer is sprayed with the help of an
by various processes including heating of the mixture, vacuum atomizer into a chamber filled with supercritical fluids. The

How to cite this article: Singh N, Sarangi M. Solid Dispersion - a Novel Approach for Enhancement of Bioavailability of Poorly Soluble Drugs in Oral Drug
004 Delivery System. Glob J Pharmaceu Sci. 2017; 3(2): 555608.DOI: 10.19080/GJPPS.2017.03.555608
 Global Journal of Pharmacy & Pharmaceutical Sciences

extraction and expansion of organic solvent into the compressed o Decomposition may take place, often dependent upon
gas result in lowering the solvent power of organic solvent for composition, fusion time and rate of cooling.
polymer as well as drug, thus leading to their precipitation.
o Sublimation or Evaporation and polymeric
Lyophilization (freeze drying) transformation of the dispersion component may takes
place.
An important advantage of freeze drying is that the drug
is exposed to a minimal thermal stress condition during the o Solidified melt may be tacky and unhandable.
formation of the SDs. However, the most important advantage
Carriers
is that the risk of phase separation is minimized as soon as the
solution is vitrified. o The properties of the carrier have been the major
influence on dissolution characteristics of dispersed drug
Electrostatic spinning method
molecules. However the carrier should meet the following
Electrostatic spinning method includes the introduction of a criteria’s to be suitable for increasing the dissolution rate of
liquid into an electric field whereas the liquid is used to develop the drug.
fibers. After withdrawal from the liquid, the fibers harden, which
o It should be water soluble with intrinsic rapid
may include mere cooling, chemical hardening or evaporation
dissolution properties.
of solvent, and then hardened fibers may be collected upon
a suitably charged surface. Tubular products comprising o It should be nontoxic and pharmacologically inert.
polyurethane fibers can be prepared by this electrostatic
o It should be heat stable with low melting point for melt
spinning method. One example of such type of tubular product is
method.
a vascular prosthesis, basically a synthetic blood vessel.
o It must be soluble in variety of solvents for evaporation
Advantages of solid dispersion
in solvent method.
Particles with reduced particle size: Molecular
o It must be able to increase the aqueous solubility of
dispersions, as solid dispersions, represents the last stage of
drug.
particle size reduction, and thus the drug possess a molecular
dispersion in the dissolution medium after the dissolution of its o It must be chemically compatible with drug and should
carrier. not possess a strong complex with it.

Particles with improved wettability: A strong contribution o It must stabilize the supersaturated solution formed
to the enrichment of drug solubility is related to the drug after dissolution of solid dispersion in GIT.
wetability improvement verified in solid dispersions. Carriers
o It must have functional groups which are either
with surface activity, such as bile salts and cholic acid, when
acceptors or donors for hydrogen bonds, as specific
used, can potentially increase the wetability properties of drugs.
interactions increase the solid solubility of the drug into its
Particles with higher porosity: Particles with solid carrier.
dispersions have been observed to have a higher degree of
o It should have high glass transition temperature.
porosity. The increased porosity of solid dispersion particles
also accelerates the drug release profile. Characterization of solid dispersion

Drugs in amorphous state: Poorly water soluble crystalline There are so many methods available for contributing
drugs, in their amorphous state tend to have a higher solubility. information regarding the physical nature of solid dispersion
However, the enhancement of drug release can usually be system [9].
obtained using the drug moiety in its amorphous state, as no Thermal Analysis Techniques
energy is required to break up the crystal lattice in the interim
of dissolution process. In case of solid dispersions, drugs are Thermal analysis comprises a group of techniques in which
conferred as supersaturated solutions after the system dissolves, a physical property of a substance is measured as a function of
and it is speculated that, if drugs precipitate, then it could be temperature, while the substance is subjected to a controlled
converted into metastable polymorphic form with a higher temperature program. In differential thermal analysis, the
solubility than its most stable crystal form. temperature difference that develops between an inert reference
material and the sample is measured, when both of them are
Disadvantages subjected to an identical heating condition.
o Carriers with High melting point cannot be used. X-ray crystallography
o Thermal degradation or instability may result at the X-ray crystallography is a substantial method for
melting point. determining the arrangement of atoms within a crystal lattice,

How to cite this article: Singh N, Sarangi M. Solid Dispersion - a Novel Approach for Enhancement of Bioavailability of Poorly Soluble Drugs in Oral Drug
005 Delivery System. Glob J Pharmaceu Sci. 2017; 3(2): 555608.DOI: 10.19080/GJPPS.2017.03.555608
 Global Journal of Pharmacy & Pharmaceutical Sciences

in which a beam of X-rays strikes on a crystal and diffracts into that in some cases led to a complete loss of NAP crystallinity.
many specific directions. A crystallographer can produce a three Ruan et al. [11] studied solubility of ampelopsin (AMP) in
dimensional picture of the density of electrons within the crystal water by two systems: solid dispersions with polyethylene
by analyzing the angles and intensities of these diffracted beams. glycol 6000 (PEG 6000) or polyvinylpyrrolidone K-30 (PVP
From this electron density, the mean positions of the atoms in K30) and inclusion complexes with β-cyclodextrin (BCD) and
the crystal can be determined, along with their chemical bonds, hydroxyl propyl-β-cyclodextrin (HPBCD).It was concluded that
disorder and various other information. improvement of solubility using polymers was in the following
order: HPBCD≈BCD> PVP K30 > PEG 6000.
Spectroscopy
Chauhan et al. [12] prepared solid dispersions (SDs)
Spectroscopy is defined as the study of the interaction
of glibenclamide (GBM); a poorly water-soluble drug and
between matter and radiation as a function of wavelength (λ).
polyglycolized glycerides (Gelucire®) with the aid of silicon
In fact, historically, spectroscopy is referred to the use of visible
dioxide (Aerosil® 200); as an adsorbent, were prepared by spray
light dispersed according to its wavelength, e.g. by a prism.
drying technique. The study demonstrated the high potential of
However in later stage the concept was expanded greatly to
spray drying technique for obtaining the stable as well as free
comprise any measurement of a quantity as a function of either
flowing SDs of poorly water-soluble drugs using polyglycolized
frequency or wavelength. Thus it also can be referred to as a
glycerides carriers with the aid of silicon dioxide as an adsorbent.
response to an alternating field or varying frequency (ν).
Heo et al. [13] prepared the polyethylene glycol (PEG)
Dissolution testing
6000-based solid dispersions (SDs), by incorporating various
Dissolution experiments can be carried out in triplicate pharmaceutical excipients or microemulsion systems, using
on the binary as well as ternary dispersions. The tests were a fusion method, to compare the dissolution rates. The
performed according to the USP 24 method 2 in a dissolution ketoconazole (KT), a potent antifungal agent, was selected to be
apparatus. To simulate the dissolution of a weak basic compound as a model drug. They found that when hydrophilic and lipophilic
in the stomach, 500ml of simulated gastric fluid without pepsin excipients were combined and incorporated into PEG-based SDs,
was used as dissolution medium at a temperature of 37 °C a remarkable enhancement of the dissolution rate was observed.
and a paddle speed of 100rpm. The amount of the spray-dried The PEG-based SDs, incorporating a self microemulsifying
powders, equivalent to the drug dose of 100mg, was added to the drug delivery system (SMEDDS) or microemulsion (ME), were
dissolution medium. also useful at improving the dissolution rate by forming a
microemulsion or dispersible particles within the aqueous
Environmental scanning electron microscopy
medium.
The morphology of the spray-dried ternary solid dispersions
Urbanetz et al. [14] prepared solid dispersions of Nimodipine
was characterized with environmental scanning electron
and polyethylene glycol 2000. It was found that the absence
microscope, operating at 25Kv of accelerating voltage in
of crystalline drug material in solid dispersions containing
association with a vacuum. The samples were sprayed on
Nimodipine and polyethylene glycol 2000 is the prerequisite for
double-sided carbon tape which was mounted on a conventional
a high dissolution rate and a remarkable super saturation in the
SEM stubs.
dissolution medium. Thus, shock freezing during the preparation
Review of literature on solid dispersion process, along with low storage temperatures and low relative
humidities are useful to prevent recrystallisation.
Dressman et al. studied on improval of drug solubility for
oral delivery by using solid dispersion. They gave an overview Costa et al. [4] thoughly studied on solid dispersion as a
of the historical background and definitions of the various strategy to improve oral bioavaibility of poorly water soluble
systems including eutectic mixtures, solid dispersions and solid drugs. They have disclosed the recent advances related to the
solutions. It is concluded that although solid solutions have area of solid dispersions. It was found that by reducing drug
tremendous potential for improving drug solubility, 40 years of particle size to the absolute minimum, and hence improving
research have resulted in only a few marketed products using drug wettability, bioavailability may be significantly improved.
this approach. Thus, with an introduction of new manufacturing Ansari et al. [15] studied the physicochemical characteristics
technologies such as hot melt extrusion, it could be possible to of polyvinyl pyrrolidone, dihydroartemisinin and their solid
overcome the problems in scale-up. dispersions which were evaluated at various proportions of drug
and polyvinylpyrrolidone. It was found that dihydroartemisinin
Mura et al. [10] studied combined effect of hydroxypropyl-
became more amorphous as drug carrier ratio was enhanced in
b-cyclodextrin (HPbCD) and polyvinylpyrrolidone (PVP) on the
solid dispersions.
solubility of naproxen (NAP). The results of solid state studies
accounted for the occurrence of mechanically- and/or thermally- Konno et al. [16] studied the effect of polymer type on the
induced stronger interactions in ternary than in binary systems, dissolution profile of amorphous solid dispersions containing

How to cite this article: Singh N, Sarangi M. Solid Dispersion - a Novel Approach for Enhancement of Bioavailability of Poorly Soluble Drugs in Oral Drug
006 Delivery System. Glob J Pharmaceu Sci. 2017; 3(2): 555608.DOI: 10.19080/GJPPS.2017.03.555608
 Global Journal of Pharmacy & Pharmaceutical Sciences

Felodipine. In the current study, the dissolution profiles of Improved drug dissolution by both the carriers may be attributed
solid dispersions of Felodipine formulated with hydroxypropyl to the reduction in drug crystallinity, improved wettability and
methylcellulose (HPMC), poly(vinylpyrrolidone) (PVP), or solubilizing effects from solid dispersions of valdecoxib.
hydroxypropyl methylcellulose acetate succinate (HPMCAS)
Almeida et al. [21] investigated the formation of finasteride:
were compared. However HPMCAS was found to maintain
PEG 6000 and finasteride:Kollidon K25 solid dispersions and
the highest level of super saturation for the greatest length
finasteride:b-cyclodextrin inclusion complexes by solvent
of time for both the dissolution and solution crystallization
evaporation method using a mixture of water:ethanol (1:1). They
experiments, whereas PVP was observed to be the least effective
concluded that dissolution rate of solid dispersions and inclusion
crystallization inhibitor. It was concluded that all polymers
complexes was significantly greater than that of pure drug as
appeared to reduce the crystal growth rates of Felodipine at
well as its corresponding physical mixtures, thus indicating the
an equivalent super saturation and this mechanism most likely
formation of solid dispersions and inclusion complexes with an
contributes to the enhanced solution concentration values
increased solubility of the poorly soluble drug, finasteride.
observed during dissolution of the amorphous solid dispersions.
Potluri et al. [22] studied the enhancement of dissolution of
Jansens et al. [17] studied physical chemistry of solid
poorly soluble carvedilol by solid dispersions (SDs) with Gelucire
dispersion. They discussed the strategies that include complete
50/13 using solvent evaporation method. From the dissolution
removal of drug crystallinity, and molecular dispersion of the
parameters such as dissolution efficiency, mean dissolution time
poorly soluble compound in a hydrophilic polymeric carrier.
and drug release rate, an improved dissolution characteristics
They concluded that to reduce development times and to arrive
for SDs were observed in comparison with physical mixture
at a more rational excipient selection strategy, understanding
and pure drug. Thus they concluded that SDs of carvedilol in
fundamental aspects of solid dispersions is imperative. Thus
Gelucire 50/13 showed enhanced solubility and dissolution rate
the formulation compounds should be selected on the basis of
compared to pure drug.
their stabilizing effect on supersaturated solutions formed upon
release, as well as their effect on the shelf life stability of the Kushwaha et al. [23] studied to improve the dissolution rate
glass solution. of Acyclovir, a poorly water soluble drug by solid dispersion
technique using a water soluble carrier, PEG-6000, urea,
Park et al. [18] studied the Physicochemical Characterizations
mannitol. The solid dispersions were developed by co-grinding
of Tacrolimus loaded Solid dispersion with Sodium Lauryl Sulfate
method, physical method and solvent evaporation method. The
and Sodium Carboxylmethyl Cellulose. They concluded that
prepared solid dispersions possess an increment in dissolution
the solid dispersion at the tacrolimus/CMC-Na/sodium lauryl
rate and solubility compared to the plain drug.
sulfate/citric acid ratio of 3/24/3/0.2 significantly improved the
drug solubility and dissolution compared to powder. Thus, the Akiladevi et al. [24] prepared solid dispersion of Paracetamol
solid dispersion system with water, sodium lauryl sulfate, citric by physical triturating method, and fusion method by using
acid and Na-CMC should be a potential candidate for conveying a 1:1, 1:4 and 1:5 ratios of drug and polymers (PEG 4000, PEG
poorly water-soluble tacrolimus with an elevated solubility and 6000 and urea). Hence it was concluded that the dissolution
no convertible crystalline. of Paracetamol could be improved by the solid dispersion and
the PEG6000 based solid dispersions were more effective in
Badry et al. [19] prepared and characterized the solid
enhancing the dissolution rate in comparison to others.
dispersions of non-steroidal anti-inflammatory drug,
Indomethacin (IND),which is basically water insoluble, with Lim et al. [25] studied an emulsified solid dispersion of
polyethylene glycol 4000 (PEG4000) and Gelucire 50/13 (Gelu.) Docetaxel. Various emulsifying pharmaceutical excipients and a
for enhancing the dissolution rate of the drug. An enhanced super saturation promoter like hydroxypropyl methylcellulose
dissolution rate of IND at pH 7.4 and 1.2 was observed when (HPMC) were introduced into the PEG6000- based solid
the drug was dispersed in these carriers in the form of physical dispersion to further improve its solubilizing capability. Kim
mixtures (PMs) or SDs. IND released faster from the SDs than et al. [26] investigated the solid dispersion formulations of
that from the pure crystalline drug or the PMs. The dissolution Mosapride with controlled release characteristic using various
rate of IND from its PMs or SDs got increased with an increasing polymers, elucidate the release mechanism, and characterize
amount of polymer. the interaction patterns between Mosapride and polymers.
The results indicated that the solid dispersion formulation
Shah et al. [20] developed solid dispersions of valdecoxib
containing PVP/Eudragit RSPO or HPMC mixture could serve as
with an objective of dissolution enhancement by melt
a good controlled- release system for Mosapride.
granulation technique by using polyvinyl pyrollidone (PVP K 30)
and polyethylene glycol (PEG 4000) in both alone (1:1) and in References
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How to cite this article: Singh N, Sarangi M. Solid Dispersion - a Novel Approach for Enhancement of Bioavailability of Poorly Soluble Drugs in Oral Drug
007 Delivery System. Glob J Pharmaceu Sci. 2017; 3(2): 555608.DOI: 10.19080/GJPPS.2017.03.555608
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How to cite this article: Singh N, Sarangi M. Solid Dispersion - a Novel Approach for Enhancement of Bioavailability of Poorly Soluble Drugs in Oral Drug
008 Delivery System. Glob J Pharmaceu Sci. 2017; 3(2): 555608.DOI: 10.19080/GJPPS.2017.03.555608