An Exhaustive Review on Solubility Enhancement for Hydrophobic Compounds by Possible Applications of Novel Techniques
Tapan Kumar Giri,
Dulal Krishna Tripathi,
Trends in Applied Sciences Research,
2012, 7(8), 596-619.
The combinatorial chemistry and high throughput screening increases the solubility
of poorly water soluble compounds. The most challenging task in development
of a formulation is the solubility of drug, availability at the site of action
and stability of drug. Aqueous solubility of any therapeutically active substance
is a key property as it governs dissolution, absorption and thus the in vivo
efficacy. Among all newly discovered chemical entities about 40% drugs are lipophilic
and these drugs are rejected by the pharmaceutical industry and will never benefit
a patient because of its poor bioavailability due to low water solubility and/or
cell membrane permeability. Drug efficacy can be severely limited by poor aqueous
solubility and some drugs also show side effects due to their poor solubility.
Therefore, drug release profiles are exhibited by such formulations for poorly
soluble drugs to improve the solubility of such poorly soluble drugs. Any drug
to be absorbed must be present in the form of an aqueous solution at the site
of absorption. Water is the solvent of choice for liquid pharmaceutical formulations.
Most of drugs which are weakly acidic and basic show poor aqueous solubility
hence various methods like, salt formation, co-solvency, micronization, addition
of agent, solid dispersion, complexation etc., are some of the vital approaches
routinely employed to enhance the solubility of poorly soluble drugs. This article
reviews various methods used for improving the solubility of hydrophobic drugs
and improve the drug release profiles which are exhibited by such formulations
for poorly soluble drugs.
Seedher and Sharma, 2007).
Since 1995, more than 90% of drugs are approved as hydrophobic having poor solubility.
A maximum amount of solute dissolved in a given solvent at a specified temperature
defined as solubility (Patil et al., 2011). The
substance which is to be dissolved is known as solute and the fluid (medium)
in which the solute to be dissolve is known as solvent and the process of dissolving
solute into solvent is called as solution. Descriptive terms for solubility
are shown in (Table 1) (Beringer, 2005).
The poorly soluble agent have low water solubility hence they low bioavailability
and absorption (Heimbach et al., 2007; Nourani
et al., 2008; Vahedi, 2012). There are various
techniques and formulations have been employed to overcome these limitations.
Although, existing strategies such as complexing drugs by using Cyclodextrins
(Vyas et al., 2008; Zhixun
et al., 2006; Sangshetti et al., 2008)
conjugation to dendrimers (Gupta et al., 2006),
salt formation of ionizable drugs (Serajuddin, 2007)
and the use of co-solvents (Akers, 2002; Strickley,
2004) have been shown to improve drug solubility. The World Health Organization
(WHO) have classified BCS classification on the basis of data as 130 orally
administer drug from which according to WHO list 61 could be classified as poorly
soluble drug (Al Omari et al., 2009) (Table
2). Biopharmaceutical Classification System (BCS) many drugs belongs to
Biopharmaceutics Classification System (BCS) class II (high permeability, low
solubility) or IV (Low permeability, Low solubility) (Amidon
et al., 1995; Porter and Charman, 2001).
For the BCS class II drugs, the oral absorption is limited by the solubility
or dissolution in gastrointestinal (GI) tract.
Solubilisation process: The breaking of inter-ionic or intermolecular
bonds in the solute occurs mainly in the method of solubilisation. In solubilisation
method the solvent provide space for the solute, interaction between solvent
and the solute molecule or ion (Fig. 1).
FACTORS AFFECTING SOLUBILITY
Polymorphs: Absorption and bioavailability can also be enhanced by polymorphs
as defined as the greater the solubility of the metastable form Blagden
et al. (2007) and Ajazuddin et al. (2011).
Polymorphs can vary in melting point. Since, the melting point of the solid
is related to solubility, the capacity for a substance to crystallize in more
than one crystalline form is polymorphism. It is possible that all crystals
can crystallize in different forms or polymorphs. If the change from one polymorph
to another is reversible, the process is called enantiotropy. If the system
is monotropic, there is a transition point above the melting points of both
polymorphs. So, polymorphs will have different solubility (Worthen,
2006; Noorizadeh and Farmany, 2011).
Particle size: The solubility of crystalline solids gets affected by
particle size it is well describe in the documented (Hammond
et al., 2007; Wu and Nancollas, 1998; Mosharraf
and Nystrom, 1995).
By reducing the particle size, the solubility of crystalline drugs can be increased
to submicron levels, but the effect of solubility is trifling if the particle
size is not reduced below 10 μm. The effect of particle size on solubility
can be described by Chaumeil (1998):
||The solubility of infinitely large particles
||The solubility of fine particles
||The surface tension of the solid
||The radius of the fine particle
Pressures: An increase in pressure increases solubility for gaseous
solute. While decreases in pressure for solids and liquid solutes, changes in
pressure have practically no effect on its solubility (Ain
et al., 2009). There are various approaches to improve the solubility
or to increase the available surface area for dissolution. These can be altered
or modified by following the methods of Leaner and Dressman
Temperature: Solubility changes with the temperature. It is demonstrated
by Pore and Kuchekar (2011), in solubilisation process
energy get absorbs then the temperature will increased and their solubility
will increases. If the temperature will increases enhance solubility decrease.
A few solid solutes are less soluble in warm solutions (Lindenberg
et al., 2004). The solubility of gases deceases with the increasing
METHOD FOR SOLUBILITY ENHANCEMENT
Particle size reduction
Micronization: Surface area for dissolution can be increases by Micronization
(Kawashima et al., 1975). Micronisation increases
the dissolution rate of drug through increased surface area but does not enhanced
equilibrium solubility. The increase in bioavailability after micronization
of drugs, e.g., by jet or ball milling Example, danazol (Liversidge
and Cundy, 1995), progesterone (Hargrove et al.,
1989), or dioxin (Jounela et al., 1975).
Nanosuspension: Nanosuspensions are sub-micron colloidal dispersion
of pure particles of drug, which are stabilized by the surfactants. (www.expresspharmapulse.com).
Nanosuspensions in aqueous or non-aqueous vehicles can be produced by bottom-up
(e.g., precipitation) or top-down (e.g., wet milling) processes (Rainbow,
2004; Douroumis and Fahr, 2006). High pressure homogenizers
such as the piston gap homogenizer have proved to be a highly successful technology
in nanosuspension formation.
Homogenization: Homogenization the required technique is used to reduce
the globule size of a coarse emulsion (Amit et al.,
2011), globule size is less than 100-200 nm (Davis et
al., 1974). Brownian movement prevents creaming because of small globule
size which also promotes good physical stability (Floyd,
1999; Chattopadhyay et al., 2011). There
are so many method used to improve the dissolution of hydrophobic drugs. High-Pressure
Homogenization (HPH) has been mostly used to reduce the particle size (Uchiyama
et al., 2011; Grau et al., 2000).
For example processing highly concentrated suspensions (Muller
et al., 2001) and preparing emulsions (Tian et
al., 2007). HPH has lot of advantages over other milling techniques
as it is very simple, time saving and an organic solvent-free process. Therefore,
HPH can be used to enhance the solubility of hydrophobic drugs such as PLH for
which usage of organic solvents is limited (Al-Haj and Rasedee,
2009; Ajazuddin and Saraf, 2010b). This method having
some advantages for Production of Solid Lipid Nanoparticles (SLNs) (Bhoyar
et al., 2012; Ajazuddin and Saraf, 2010a).
The objective of this study was to investigate solid lipid nanoparticles using
Carbopol gel as gelling agent containing triamcinolone acetonide acetate (glucocorticoid
compound) for transdermal iontophoretic delivery Solid Lipid Nanoparticles (SLN)
(Mehnert and Mader, 2001; Muller
et al., 2001) have been introduced to the literature as a carrier
system for poorly water soluble pharmaceutical drugs (Ugazio
et al., 2002; Westesen et al., 1997;
Lokhande et al., 2006; Nourani
et al., 2008) and cosmetic active ingredients.
Wet milling: Active drug in the presence of surfactant is defragmented
by milling (Aulton, 2002). Other technique involves the
spraying of a drug solution in a volatile organic solvent into a heated aqueous
solution. Rapid solvent evaporation produces drug precipitation in the presence
MODIFICATION OF THE CRYSTAL HABIT (Hite et al.,
Polymorphs: Polymorphism is the ability of compound to crystallize in
more than one crystalline form. Different polymorphs of drugs are chemically
identical, but they exhibit different physicochemical properties including solubility,
melting point, density, texture, stability etc. Generally, the anhydrous
form of drug has greater solubility than the hydrates. This is because the hydrates
are already in interaction with water and therefore, have less energy for crystal
breakup in comparison to the anhydrites (i.e., thermodynamically higher energy
state) for further interaction with water (Hammond et
al., 2007; Chattopadhyay et al., 2011).
DRUG DISPERSION IN CARRIERS
Solid dispersion technique: The concept of solid dispersions was given
by Sekiguchi and Obi (1961) who investigated the generation
and dissolution performance of eutectic melts of a sulfonamide drug and a water-soluble
carrier in the early 1960s (Tapas et al., 2011;
Giri et al., 2010; Zhixun
et al., 2006). Many of the drugs belongs to these techniques; can
be categorized as class II according to the Biopharmaceutical Classification
System (BCS). These drugs are poorly water soluble but once they are dissolved
they get easily absorbed through the gastro-intestinal membrane. One of the
approaches to enhance the dissolution rate is the use of solid dispersion. Some
marketed formulation of solid dispersion shown in (Table 3).
Definition of solid dispersions: The two different components, generally
a hydrophilic matrix and a hydrophobic drug mainly consist of solid dispersion
(Chiou and Riegelman, 1971). These matrix are either
crystalline or amorphous. In both particle (amorphous particles or crystalline
particles) the drug can be dispersed molecularly (Ajazuddin
et al., 2011). Solid dispersion is describing the most promising
method to improve the oral bioavailability of hydrophobic drugs by preparing
Lipid Nano Spheres (LNSs) (Amarji et al., 2007).
There are different approaches which can be used for increasing the dissolution
hydrophobic drugs of t he as given in the figure Fig. 2. That
describes the approaches to Increase solubility/Dissolution (Verma,
2011; Patidar et al., 2010).
|| Approaches to increase solubility/dissolution (Verma,
||Phase diagram of a simple eutectic mixture with negligible
solid solubility, (Sharma et al., 2009).T
A: M.P. of solid A (in °C), T B: M.P. of solid B (in °C ), TE: Eutectic
Categories of solid dispersions
Simple eutectic mixtures: The two components which are completely
miscible in a liquid state but only to a very limited extent in the solid state
forms a simple eutectic mixture (Fig. 3) (Sharma
et al., 2009). When, a composition E with a mixture of A and B is
cooled, at first A and B crystallize out simultaneously, whereas when other
compositions are cooled, one of the components starts to crystallize out while
after that when composition E is further cooled one component starts to crystallize
out before the others (Goldberg et al., 1966).
Solid eutectic mixtures are usually prepared by rapid cooling of a co-melt of
the two compounds in order to obtain a physical mixture of very fine crystals
of the two components. When a mixture with composition E, consisting of a slightly
soluble drug and an inert, highly water soluble carrier, is dissolved in an
aqueous medium, the carrier will dissolve rapidly, releasing very fine crystals
of the drug. Where T A-M.P. of solid A (in °C), T B-M.P. of solid B (in
°C), TE-Eutectic Point.
Solid solution: Solid solutions of a poorly water soluble drug dissolved
in a carrier with relatively good aqueous solubility are of particular interest
as a means of improving oral bioavailability (Leaner and
Dressman, 2000). Two components crystallize together in homogenous one phase
system. Particle size of drug in solid solution is reduced to its molecular
size. Solid solutions shows faster dissolution rate than eutectic mixtures.
Solid solutions can be divided in two types, according to their miscibility
(continuous versus discontinuous solid solutions) or, according to the way in
which the solvate molecules are distributed in the solvendum (substitutional,
interstitial or amorphous).
Continuous: The continuous solid solution consists of totally miscible components
both in liquid and solid state (Giri et al., 2010).
The pure components in a solid state lattice energy as compare to continuous
solid solution it is due to the higher heteromolecular bonding than the homomolecular
one in a continuous solid solution (Fig. 4) shows the hypothetical
phase diagram of a continuous solid solution.
Discontinuous solid solutions: Discontinuous solid solutions, the miscibility
or solubility of one component is restricted in other (Fig. 5)
shows a typical phase diagram of a discontinuous solid solution. α and
β shows the regions of true solid solutions. The region labeled β
is a solid solution of B in A that is component A would be regarded as the solvent
and B as the solute. Similarly the region labeled β is a solid solution
of A in B (Goldberg et al., 1965).
The way in which the solvate molecules are distributed in the solvendum
Substitutional crystalline solid solutions: A substitution crystalline
solid dispersion is a type of solid solutions which is having a crystalline
structure, in that the solute molecules substitute for solvent molecules in
the crystal lattice. Substitution is only possible when the size of the solute
molecules differs by less than 15% or so from that of the solvent molecules
(Fig. 6) Substitutional solid solution.
Interstitial crystalline solid solutions: In interstitial solid solutions,
dissolved molecules occupy the interstitial spaces between the solvent molecules
in the crystal lattice. As in the case of substitutional crystalline solid solutions,
the relative molecular size is a crucial criterion for classifying the solid
|| Hypothetical phase diagram of a continuous solid solution
(Giri et al., 2010)
|| Interstitial solid solution
In the case of interstitial crystalline solid solutions, the solute molecules
should have a molecular diameter that is no greater than 0.59 of the solvent
molecule's molecular diameter Furthermore, the volume of the solute molecules
should be less than 20% of the solvent (Fig. 7) Interstitial
Amorphous solid solution: It is demonstrated, that drug with propensity
to super cooling has more tendency to solidify as an amorphous form in presence
of carrier (Nikhil, 2010). This is quite similar to
simple eutectic mixtures but only difference is that drug is precipitated out
in an amorphous form. Ex. Precipitation of sulfathiazole in crystalline urea
(Fig. 8), amorphous solid solution (Table 4)
and classification of Solid Dispersions according to Molecular arrangement (Gavali
et al., 2011).
|| Classification of solid dispersions according to molecular
arrangement (Sonpal et al., 2011)
|A*: Matrix in the amorphous state, C*: Matrix in the crystalline
state, A**: Drug dispersed as amorphous clusters in the matrix, C**: Drug
dispersed as crystalline particles in the matrix, M**: Drug molecularly
dispersed throughout the matrix
Glass solutions: Solute dissolves in glass carrier to form a homogeneous
glassy system is known as glass solutions (Swarbrick, 2006;
Kim et al., 2010). Glass suspensions are mixture
in which precipitated particles are suspended in glass solvent. Different characteristics
of glassy state are brittleness, transparency below the glass transition temperature.
Lattice energy (barrier to rapid dissolution) is much lower in glass solution
and suspension. Ex-Carriers for glass solution and suspension-citric acid, sugars
(dextrose, sucrose and galactose), PVP, PEG and urea (British
Pharmacopoeia, 2007; Van Drooge et al., 2004)
(Table 4) Different carriers used for the preparation of solid
dispersion (Naveen et al., 2010) (Fig.
9) Schematic picture of the variation of enthalpy (or volume) with temperature.
TG-glass transition temp, T f-M.P. of material.
METHODS OF PREPARATION OF SOLID DISPERSIONS
Hot melt method: A process of transferring a powder blend of drug and
carrier by a rotating screw, through the heated barrel of an extruder and pressing
the melt through a die into a product of uniform shape is known as Hot-Melt
Extrusion (HME) or fusion method (McGinity and Zhang, 2003).
||Schematic picture of the variation of enthalpy (or volume)
with temperature (Shujun et al., 2006) Tag:
Glass transition temp, To: M.P. of material
HME was first introduced in the plastics industry in the mid-nineteenth century
to apply polymeric insulation coatings to wires (Crowley
et al., 2007). First applications of HME were realized as a manufacturing
tool in the pharmaceutical industry (Chaudhuri, 2007).
Solvent evaporation method: The process which involve solubilization
of drug and carrier in a volatile solvent which is later evaporated is termed
as Solvent Evaporation Method (SEM). (Hasegawa et al.,
1985; Lloyd et al., 1999; Lima
et al., 2008). In this method, the thermal decomposition of drugs
or carriers can be prevented, since organic solvent evaporation occurs at low
temperature (Won et al., 2005; Gupta
et al., 2008; Singh et al., 2011).
Solvent evaporation method is popularly used for preparation of microsphere
because of its simplicity, fast processing and reproducibility with minimum
controllable process variables that can be easily implemented at the industrial
level. Many studies have been done on solid dispersions of Meloxicam (Chokshi
and Hossein, 2004; Leila et al., 2011), Naproxen
and (Mullins and Macek, 1960), by solvent evaporation
Fusion method: A method in which a molten mixture of drug and carrier
are cooled to solidification, is called as fusion method it is also called as
solvent method in which precipitation of drug and carrier from a common solvent
occur. Paracetamol solid dispersion with PEG 8000 was prepared by melt fusion
method (Khan et al., 2011).
Melting solvent method: This involves dissolution of drug in a minimum
amount of an organic solvent, which is then added to the molten carrier (Chiou
and Riegelman, 1969; Gupta and Moorthy, 2007). Melting
solvent method (melt evaporation) method is used to prepare spironolactone-polyethylene
glycol 6000 solid dispersion without removing the solvent. They mention that
5-10% (w/w) of liquid compound could be incorporated into polyethylene glycol
6000 without significant loss of its solid property (Table 5).
Some resent patent on solubility enhancement using solid dispersion technique
(Schroeder, 2009; Ajazuddin and Saraf,
2011) has been shown in Table 5.
Cyclodextrins (CD) is a group of cyclic oligosaccharides, known for their ability
to form inclusion complexes with a variety of organic molecules (Saenger
et al., 1984; Khan et al., 2001) Complexation
by Cyclodextrins, especially the most commonly available β-Cyclodextrins,
is widely used to increase the solubility of drug molecules which have limited
solubilities in water (Abou-Auda et al., 2006).
|| Some resent patent on solubility enhancement using solid
dispersion technique (Schroeder, 2009)
|| List of complexing agents
Cyclodextrins Can also be used to prevent drug-drug interaction, it Convert
liquid drug in to microcrystalline powders, decreases volatility, modify gastrointestinal
or ocular irritation and mask of objectionable taste or odor of drug. Cyclodextrins
of pharmaceutical relevance contain 6, 7 or 8 dextrose molecules (α, β,
γ-Cyclodextrins) bound in a 1, 4-configuration to form rings of various
diameters. The ring has a hydrophilic exterior and lipophilic core in which
appropriately sized organic molecules can form noncovalent inclusion complexes
resulting in increased aqueous solubility and chemical stability. Complexation
is occurring between two or more molecules to form a nonbonded entity with a
well defined stoichiometry. Complexation relies weak forces such as London forces,
hydrogen bonding and hydrophobic interactions. The Inclusion complexes can induce
modification of the physicochemical properties of the guest molecules, particularly
in terms of water solubility and solution stability (Lyng
et al., 2004). Complex Formation by Cyclodextrins shown in Fig.
10 (Khan et al., 2001). Different method
are used to prepare inclusion complexes of a variety of drugs in order to improve
their solubility and dissolution rate. E.g., Co-precipitation, kneading and
solid dispersion methods (Shujun et al., 2006).
There are many types of complexing agents and a partial list can be found in
SOLUBILISATION BY SURFACTANTS
Surfactants are known to play a vital role in pharmacy because it have an ability
to increase the solubility of poorly soluble drug in water (Gharaei-Fathabad,
2011; Moghaddam and Moghaddam, 2011).
One of important property of surfactants is the formation of colloidal-sized
clusters in solutions, called as micelles which is having a particular significance
in pharmacy. Surfactant having the characteristic property of reducing the interfacial
and surface tension using the same mechanism as chemical surfactant. Surfactants
are the molecules with distinct no Polar Regions (Emara
et al., 2002). Most surfactants consist of a hydrocarbon segment
connected to a polar group. The polar group can be cationic, anionic, nonionic
or zwitterionic. When small polar molecules are added they can accumulate in
the hydrophobic core of the micelles. This technique of solubilization is very
important in biological and industrial processes (Gavali
et al., 2011). This work was investigated to develop the carvedilol
tablets, allowing fast, reproducible and complete drug dissolution, by using
Microemulsions: The concept of microemulsion was first introduced by
Hoar and Schulman (1943). A monodispersion spherical
droplets consisting of oil, surfactant, co-surfactant and aqueous phase, which
is optically isotropic and thermodynamically stable with a droplet diameter
within the range of 10-100 nm is defined as microemulsion (Tenjarla,
1999; Yazdani and Hadianfard, 2012). Microemulsions
could enhance the potential solubilization of hydrophobic drugs (Yin
et al., 2009; Alexander et al., 2011a).
Amongst the various drug delivery systems, the microemulsion system is considered
as an ideal alternative for the oral delivery of lipophilic drug.
Self micro emulsifying drug delivery systems: For the improving solubility,
dissolution and oral absorption of hydrophobic drugs self- micro emulsifying
drug delivery systems (SMEDDS) have been preferred (Breitenbach
et al., 2002; Cui et al., 2005). SMEDDS
is a isotropic mixtures of an oil, surfactant, co surfactant or (solubilizer)
and drug. The basic principle of this system is its ability to form fine oil-in-water
(o/w) microemulsions under gentle agitation following dilution by aqueous phases.
Self emulsifying drug delivery systems (SEDDS): An isotropic mixture
of oils, surfactants, along with co-solvents/surfactants that have a unique
ability of forming fine oil-in-water (o/w) micro emulsions upon moderate mixing
of these ingredients in aqueous media, such as GI (Gastro Intestinal) fluids
is termed as Self Emulsifying Drug Delivery Systems (SEDDS) (Agrawal
et al., 2012). It is the most useful technology to improve the rate
and extent of this poorly water soluble drug. SEDDS is a mixture of oil, surfactant
and if necessary a solubiliser. Self emulsification is initiated under gentle
agitation following contact with aqueous phase and forms a thermodynamically
stable o/w microemulsion with particle diameter of 100 nm or less. They are
reputed to improve the oral bioavailability of poorly water soluble drug (Obitte
et al., 2008; Ajazuddin and Saraf, 2010b).
CHEMICAL MODIFICATIONS (Rytting et al., 2005)
Salt formation: For enhancement solubility and dissolution rates of
acidic and basic drugs salt formation is the most common and effective method
(Serajuddin, 2007). Salts of acidic and basic drugs
have, in general, higher solubility than their corresponding acid or base forms.
Salt formation to enhance the aqueous solubility is the most preferred approach
for the development of liquid formulations for parenteral administration (Sweetana
and Akers, 1996; Lakade and Bhalekar, 2010).
Co-crystallization: The crystalline material that consists of two or
more molecular and electrical neutral species held together by non-covalent
forces is termed as co-crystallization (Masuda et
al., 2012). The non-ionizable drugs can be form due to the co crystal,
which cannot undergo in salt formation (Childs et al.,
2007). By the addition, for ionizable drugs, the number of suitable co crystal
formers can exceed the number of suitable salt formers. For example, the ionizable
drug piroxicam has more than 50 reported co crystal formers (Tran
et al., 2010).
Co-solvent: Non-aqueous co-solvent systems have been evaluated for their
potential use in the freeze-drying of pharmaceutical products. Co-solvents have
been reported to affect the rate of the organic phase partitioning into the
external aqueous phase and thus, influence the physicochemical properties and
release kinetics of PLGA microspheres (Rudra et al.,
2011; Singh et al., 2011).
Hydrotropic: For drug aqueous solubility hydrotropic solubilization
is an important technique (Shibata et al., 2009).
Since 1916, New berg, was first suggested the term hydrotropic which is used
to designate anionic organic salts which, at high concentrations, considerably
increase the aqueous solubility of poorly soluble solutes. Hydrotropes dissolved
in water which can produce high degree solubility enhancement of hydrophobic
drugs (Trana et al., 2011). For enhancement of
aqueous solubility of hydrophobic drugs hydrotropic agents have
been found to be more effective and hence can play important role for improving
the oral bioavailability (Maheshwari and Jagwani, 2011;
Alexander et al., 2011b) (Table
7). Hydrotropic is a molecular phenomenon where by adding a second solute
(the hydrotropic) results in an increase in the aqueous solubility of poorly
soluble solutes (Nidhi et al., 2011) (Table
8) provide the example of some drug which Enhance the solubility by using
||Hydrotropic is a molecular phenomenon where by adding a second
solute results in an increase in the aqueous solubility of poorly soluble
solutes (Bobe et al., 2011)
||Example of some drug which Enhance the solubility by this
The stability of the drug, its solubility and availability at the site of action,
is very important particularly when the formulation is intended for oral administration.
Solubility and dissolution can be subsequently affecting the in vivo
absorption of drug. So, it is very important to improve the aqueous solubility
drugs. By reviewing this article we conclude that, solubility is a most important
parameter for the oral bioavailability of hydrophobic. Solubility is also the
basic requirement for the formulation and development of different dosage form
of different drugs. Solubility can be enhanced by many techniques and number
of folds increase in solubility is reported too. Because due to the solubility
and stability problem of many drugs the bioavailability of them gets affected
and hence solubility enhancement becomes necessary. It is now possible that
to increase the solubility of hydrophobic drugs with the help of various techniques
as mentioned above.
The authors would like to acknowledge the assistance provided by the Library
of Rugnta College of Pharmaceutical
Sciences and Research, Kohka-kurud Road, Bhiali, C.G. (India) for collection
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