Vinay ejpmr

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LIQUISOLID TECHNIQUE: A NOVEL CONCEPT OF DRUG DELIVERY SYSTEM TO
ENHANCE DISSOLUTION
Vinay A. P.*, Mamatha G. T., Parthiban S. and Senthil Kumar G. P.
Department of Pharmaceutics, Bharathi College of Pharmacy, Bharathinagar, Maddur Taluk, Mandya District,
Karnataka, India.
Article Received on 07/05/2019 Article Revised on 28/05/2019 Article Accepted on 19/06/2019
INTRODUCTION
Solubility or dissolution is a most discussed but still not
completely resolved issue for the researchers in
formulation science. Dissolution and solubility are the
core concepts of any physical or chemical science
including biopharmaceutical and pharmacokinetic
considerations in therapy of any medicine. The
solubility/dissolution behaviour of a drug is key
determinant to its oral bioavailability, the latest
frequency being the rate-limiting step of absorption of
drugs from the gastrointestinal tract. As a result, more
than 40% of new candidates entering drug development
pipeline fail because of non-optimal biopharmaceutical
properties.[1]
Different techniques are employed to improve the
dissolution characteristics of poorly aqueous soluble
drugs, which include, (a) solubilisation in surfactants (b)
particle size reduction (c) co-solvents (d) micro emulsion
(e) self emulsification (f) polymeric modification (g)
drug complexation (h) pH adjustment (i) the pro-drug
approach and (j) solid solutions. Liquisolid system is the
most promising method for promoting dissolution.[2]
Liquisolid system refers to formulations made by
conversion of liquid drugs, drug suspensions or drug
solution in non-volatile solvents into dry, non-adherent,
free-flowing and compressible powder admixtures by
mixing the suspension or solution with selected carriers
and coating materials. Since drugs are solubilised in a
molecular state, with the enormously increased surface
area, water-insoluble substances may be expected to
reveal increased drug release characteristics with
improved oral bioavailability. This technique can also be
used in sustained release of water soluble drugs from
tablet matrices by the usage of hydrophobic carriers.[3]
Classification
A. Based on the type of liquid medication contained
therein, liquisolid systems may be classified into three
subgroups
1. Powdered drug solutions
2. Powdered drug suspensions
3. Powdered liquid drugs
The first two may be produced from the conversion of
drug solutions or drug suspensions and latter from the
formulation of liquid drugs into liquisolid systems.
B. Based on the formulation technique used, liquisolid
systems may be classified into two categories, namely,
1. Liquisolid compacts
2. Liquisolid Microsystems
Liquisolid compacts are prepared using the previously
outlined method to produce tablets or capsules, whereas
SJIF Impact Factor 4.897
Review Article
ISSN 2394-3211
EJPMR
EUROPEAN JOURNAL OF PHARMACEUTICAL
AND MEDICAL RESEARCH
www.ejpmr.com
ejpmr, 2019,6(7), 270-274
ABSTRACT
Dissolution of drug and its release from the dosage form have basic impact on bioavailability. Bioavailability of
drugs depends on its solubility. Solubility is major challenge for the pharmaceutical industry with the developments
of new pharmaceuticals. About 40% of the newly discovered drugs fall into poor water soluble or water insoluble
categories. The aqueous solubility of poorly water-soluble drugs is usually less than 100ug/ml. There are so many
techniques to enhance the dissolution of poorly soluble drugs, in which the liquisolid compacts is a promising
technique. The Liquisolid compact system is a novel concept of drug delivery system (NDDS) that can improve the
dissolution rate of water insoluble drugs. This liquisolid technique is based upon dissolving the insoluble drug in
the non-volatile solvent and admixture of drug loaded solutions with appropriate carrier and coating materials to
convert into acceptably flowing and compressible powders. These free flowing powders are subjected to
compression for tablet or filled in capsules.
KEYWORDS: Liquisolid Compacts, Non-Volatile Solvent, Carrier, Coating Material.
*Corresponding Author: Vinay A. P.
Department of Pharmaceutics, Bharathi College of Pharmacy, Bharathinagar, Maddur Taluk, Mandya District, Karnataka, India.

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the liquisolid Microsystems are based on a new concept
which to produce an acceptably flowing admixture for
encapsulations.[4]
MATERIALS AND METHOD
Drug candidate: Mainly liquisolid technique is used for
drug candidates comes under class II and class IV drugs.
These drugs has low aqueous solubility and low
dissolution rate. By using liquisolid technology
dissolution rate of such poorly soluble drugs get
improved by improving their solubility.
e.g.
Drug Category
Nimesulide NSAID
Telmisartan Anti-hypertensive
Prednisolone Anti-asthmatic
Curcumin Anti-cancer
Famotidine H2-Blocker
Spironolactone Diuretics
Indomethacin NSAID
Non volatile solvent
Ideal characteristics non volatile solvent
 It should be inert.
 It should have high boiling point.
 It should be preferably water miscible.
 It should not be highly viscous organic solvent system.
 It should be compatible with having ability to
solubilise the drug.
 The non volatile solvents used in the liquisolid system
mainly acts as binding agent.
e.g. PEG 200, PEG 400, Polysorbate 80, Propylene
glycol, Glycerine etc.
Carrier materials: Carrier materials should be
sufficiently porous so that can enhance absorption
properties and hence can absorb liquid sufficiently to
enhance the solubility. e.g. Avicel PH 102 and 200,
Eudragit RL and RS, starch, cellulose, lactose, sorbitol
etc.
Disintegrant: Mainly superdisintegrants increases rate
of drug release, its wettability and increases solubility of
drug particles within short period of time. e.g. Sodium
Starch Glycolate (SSG), Crosspovidone etc.
Coating material: Coating material should be with high
adsorptive property so that when used for coating the
carrier particles can absorb the excessive non volatile
solvent layer over the carrier particles and can give dry
solid appearance to the saturated carrier particles having
liquid external layer of non volatile solvent. This can
give dry, non adherent, free flowing powder particles.
e.g. Silica of various grades like Cab-o-Sil M5, Aerosil
200, Syloid 244 FP etc.[5,6]
Preformulation studies
1. Solubility of drug: It is carried out by preparing
saturated solution of drug in different solvents. This
saturated solution is prepared by adding excess amount
of drug in non solvent. This solution is shaken with
shaker for specific period of time than it is filtered and
analyzed under UV spectrophotometer.
2. Determination of angle of slide: Angle of slide is
used as a measure of the flow properties of powders.
Determination of angle of slide is done by weighing the
required quantity of carrier material and placed at one
end of a metal plate with a polished surface. The end is
gradually raised till the plate becomes angular to the
horizontal at which powder is about to slide. This angle
is known as angle of slide. Angle of 33º is regarded as
optimum.
3. Determination of flowable liquid retention potential
(Φ value): The term "flowable liquid-retention potential"
(Φ-value) of a powder material describes its ability to
retain a specific amount of liquid while maintaining good
flow properties. The Φ-value is defined as the maximum
weight of liquid that can be retained per unit weight of
the powder material in order to produce an acceptably
flowing liquid/powder mixture. The Φ values are
calculated according to the following equation.
4. Calculation of liquid load factor (Lf)
Different concentrations of non-volatile solvents are
taken and the drug is dissolved. Such liquid medication
is added to the carrier coating material admixture and
blended. Using equation (2) drug loading factors are
determined and used for calculating the amounts of
carrier and coating materials in each formulation.
5. Liquisolid compressibility test (LSC)
Liquisolid compressibility test is used to determine Φ
values and involves steps such as preparing carrier
coating material admixture systems, preparing several
uniform liquid or powder admixtures, compressing each
liquid or powder admixtures to tablets, assessing average
hardness, determination of average liquid content of
crushed tablets, as well as determining plasticity, sponge
index and Φ value and LF.[7]
Formulation
General Procedure for Liquisolid Tablets: The
Liquisolid tablet preparation method involves, first a
mathematically calculated amount of pure drug weighed
and dissolved in the suitable amount of solvent in a
molecularly dispersed state. For attaining good flow
properties trial and error methods were used i.e.
changing the carrier and coating material ratio from 50:1
to 5:1 ratios according to new mathematical model

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expressions proposed by Liao. This liquid medication is
poured on the suitable amount of carrier material. The
liquid medication is absorbed into the carrier material
internally and externally and then a suitable disintegrates
was added to this material. Finally, coating material was
added for dry looking, adherent to the carrier material for
achieving good compression properties. Liquid
medication is incorporated into carrier material which
has a porous surface and closely matted fibers in its
interior as cellulose. Both absorption and adsorption take
place, i.e. first, the liquid absorbed into the interior of the
particles is captured by its internal structure, and after
saturation of this process, adsorption of the liquid onto
the internal and external surface of the porous carrier
particles occurs. A large surface area and high absorptive
properties of the coating material gives the Liquisolid
system the particular flow properties described (Martin et
al., 1983; Spireas et al., 1992).[8]
Evaluation Studies
Micromeritic Property of Powder
Bulk Density: The bulk density and tapped density were
determined by using bulk density apparatus apparent
bulk density was determined by pouring the blend into a
graduated cylinder. The bulk volume (Vb) and weight of
the powder (M) was determined. The bulk density was
calculated using the formula.
Tapped density: The measuring cylinder containing a
known mass of powder blend was tapped for a fixed
number of times as per USP apparatus-11. The minimum
volume occupied by the powder after tapping was
measured
Corr’s index: Corr’s index is calculated as follows
The value below 15% indicates a powder with good flow
characteristics whereas above 25% indicates poor
flowability.
Haussner’s ratio: It is an indirect index of ease of
powder flow, it is calculated as follows.
Haussner’s ratio <1.25 indicates good flow property,
where as >1.5 indicates poor flowability.
Angle of Repose: Angle of repose was determined using
funnel method. The blend was poured through funnel
that can rise vertically until a maximum cone height (h)
was obtained. Radius of the heap(r) was measured and
angle of repose was calculated as follows[9,10]
Precompression studies of the prepared liquisolid
Powder systems: In order to ensure the suitability of the
selected excipients, Fourier Transform Infra Red
Spectroscopy, Differential scanning Calorimetry, X-ray
Diffraction and Scanning Electron Microscope studies
are to be performed. In addition, flowability studies are
also to be carried out to select the optimal formulae for
compression, prior to the compression of the powders the
dosage forms such as into tablets and capsules.
Differential scanning calorimetry (DSC): It is
necessary to determine any possible interaction between
excipients used in the formulation. This will also indicate
success of stability studies. If the characteristic peak for
the drug is absent in the DSC thermogram, there is an
indication that the drug is in the form of solution in
liquisolid formulation and hence it is molecularly
dispersed within the system.
X-RAY powder diffractometry (XRPD): For the
characterization of crystalline state, X-ray diffraction
(XRD) patterns are determined for physical mixture of
drug and excipients used in formulation and for the
prepared liquisolid compacts. Absence of constructive
specific peaks of the drug in the liquisolid compacts in
X-ray diffractogram specify that drug has almost entirely
converted from crystalline to amorphous or solubilised
form. Such lack of crystallinity in the liquisolid system
was understood to be as a result of drug solubilisation in
the liquid vehicle i.e., the drug has formed a solid
solution within the carrier matrix. This amorphization or
solubilization of drug in the liquisolid compacts it may
contribute to the consequent improvement in the
apparent solubility and enhancement of dissolution rate
of the drug.
Fourier transformed infra red spectroscopy (FT-IR)
FT-IR spectra of prepared melt granules are recorded on
FTIR-8400 spectrophotometer. Potassium bromide (KBr)
pellet method is employed and background spectrum is
collected under identical situation. Each spectrum is
derived from single average scans collected in the region
400 - 4000cm-1 at spectral resolution of 2cm-2 and ratio
against background interfereogram. Spectra are analyzed
by software.
Scanning electron microscopy (SEM): Scanning
electron microscopy shows that there is presence or
absence of crystal form of the drug or excipients in the
formulation. If SEM shows that there is absence of
crystal form of the drug then it shows that now the drug
is completely solubilised in to carrier system. After
complete formulation liquisolid tablets also get evaluated
for wt. variation, thickness, friability, moisture content

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(by using Karl Fischer‟s method), disintegration test,
dissolution test and content uniformity.[11,12]
Post compression test.
Estimation of drug content: The liquisolid compacts
are powdered well and equivalent to 10mg of the drug
powder is weighed and diluted using suitable solvent.
The drug content is analyzed using UV-Visible
spectrophotometer.
Hardness of tablet: Tablet hardness and strength are the
essential to see that the tablet can with the shock and
stress during manufacturing packing and transportation,
and while handled by the patient. Tablet hardness should
lies between 5 to 10 kg/cm2
.
Weight variation test: Weight variation test is
performed to check that the manufactured tablets have a
uniform weight. Procedure: Weigh individually 20 units
selected at random and calculate the average weight. Not
more than two of the individual weights deviate from the
average weight by more than the percentage given in the
pharmacopoeia and none deviates by more than twice
that percentage.
Friability: Friability is the phenomenon where the
surface of the tablet is damage or shown a site of damage
due to mechanical shock. It is tested by using Roche
friabilator. According to B.P/I.P = Percentage of
friability should be not more than 0.8% - 1.0%
According to U.S.P = Percentage of friability should be
not more than 4%.[13,14]
In vitro release: In vitro release of liquisolid tablets is
carried out by using USP II apparatus at 37 0
C ± 2 0
C.
During this study many researchers observed that if there
is low drug concentration in liquid formulation then there
is rapid drug release from the formulation. If In vitro
release rates for liquisolid tablets are higher than the
absorption rate will also be higher which enhances drug
bioavailability.
In vivo study: This liquisolid technology is a promising
tool for the enhancement of drug release of poorly
soluble drugs. The absorption characteristics of
Hydroclorothiazide liquisolid compacts in comparison
with commercial tablets were studied in beagle dogs.
Significant differences in the area under the plasma
concentration time curve, the peak plasma concentration
and the absolute bioavailability of the liquisolid and the
commercial tablets were observed. However, for the
mean residence time, the mean absorption time, and the
rate of absorption no significant differences were found.
The absolute bioavailability of the drug from liquisolid
compacts was 15% higher than that from the commercial
formulation.[15]
Advantages of Liquisolid Compact
1. Number of poorly water-soluble and water-insoluble
liquid and solid drugs such as Digitoxin, Prednisolone
and Hydrocortisone etc. can be formulated into liquisolid
systems using the new formulation-mathematical model.
2. Though the drug is in a tabletted or encapsulated
dosage form it is held in a solubilized liquid state, which
consequently contributes to enhanced drug wetting
properties, thereby increasing drug dissolution.
3. Production cost of liquisolid systems is lower than that
of soft gelatin capsules.
4. Optimized rapid-release liquisolid tablets or capsules
of water-insoluble drugs exhibit enhanced in-vitro and
invivo drug release as compared to their commercial
counterparts.
5. Optimized sustained-release liquisolid tablets or
capsules of water-insoluble drugs exhibit surprisingly
constant dissolution rates (zero-order-release)
comparable only to expensive commercial preparations
that combine osmotic pump technology and laser-drilled
tablets.[16]
Disadvantages of Liquisolid Technique
1. Liquisolid systems require high solubility of drug in
nonvolatile solvents.
2. High levels of carrier material and coating materials
should be required in order to achieve acceptable
flowability and compactibility for liquisolid powder
formulation.
3. Liquisolid system is the problematic formulation of a
high dose of poorly water soluble drugs (e.g.,
carbamazepine, budesonide).[17]
CONCLUSION
Various methods are studied to improve water solubility
and drug release, among which the liquisolid technology
is one of the most promising approaches. Liquisolid
system refers to the conversion of liquid drugs, drug
suspensions or drug solution in non-volatile solvents into
dry, non-adherent, free-flowing and compressible
powder mixtures by blending the suspension or solution
with selected carriers and coating materials. This
technique enhances the solubility and bioavailability of
poorly water soluble drugs. This technique can also be
used to effect the sustained release of water soluble drugs
from tablet matrices by the usage of hydrophobic
carriers.
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