Table of Contents  
Year : 2012  |  Volume : 3  |  Issue : 2  |  Page : 95-105  

A basic insight into the stability and manufacturing aspects of solid dispersions

1 Department of Pharmaceutics, School of Pharmacy, Suresh Gyan Vihar University, Jaipur, India
2 Department of Pharmaceutics, Grace College of Pharmacy, Calicut University, Kerala, India

Date of Web Publication18-Jul-2012

Correspondence Address:
Ritu M Gilhotra
Head of Department, Department of Pharmaceutics, School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2229-5186.98668

Rights and Permissions

The development of a bioavailable dosage form is the most challenging task for the researchers. In the arena of advanced drug delivery systems, the solid dispersion techniques seem to be a promising system for the development of an optimized, bioavailable formulation of Class 2 drugs. The methods of formulation of solid dispersion have been summarized. This article is an effort to define a solid dispersion and its classification. The prospective of the stability of solid dispersion has also been discussed. Moreover, the major techniques that have been used so far such as the fusion/melting method, solvent evaporation method, hot melt extrusion method, supercritical fluid methods, have also been detailed.

Keywords: Fusion method, hot melt extrusion method, solid dispersion, solvent evaporation method, stability of solid dispersion, supercritical fluid methods

How to cite this article:
Vijay J, Sahadevan JT, Gilhotra RM. A basic insight into the stability and manufacturing aspects of solid dispersions. Chron Young Sci 2012;3:95-105

How to cite this URL:
Vijay J, Sahadevan JT, Gilhotra RM. A basic insight into the stability and manufacturing aspects of solid dispersions. Chron Young Sci [serial online] 2012 [cited 2020 Jan 22];3:95-105. Available from:

   Introduction Top

One of the most important problems faced by the drug formulators all over the world is the poor solubility of drug candidates. Most of the work currently going on in the drug formulation technology field is mainly concentrated on increasing the solubility characteristics of the drug synthesized. Development of an optimized, bioavailable formulation of a particular drug is a Herculean task. 40% of the drugs newly synthesized by the chemists belong to the category of poorly soluble drugs. [1],[2] Development of bioavailable dosage form of these drugs is the most important challenge faced by the formulators. The oral route of administration is the most convenient and preferred method of drug delivery. At least 90% of all drugs used to produce systemic effects are administered by oral route. Of drugs that are administered orally, solid dosage forms represent the preferred class of product. After oral administration, factors like fraction of drug reaching the systemic circulation determine the bioavailability of the drug. In solid dispersion, a portion of drug dissolves immediately to saturate the gastrointestinal (GI) tract fluid and excess drug precipitates as fine colloidal particles or oily globules of submicron size. [3] A drug can be orally delivered only if it has good dissolution profile in GI fluids before it can pass through the membrane of GI tract to reach systemic circulation. According to Biopharmaceutical Classification System (BCS), drugs are classified into four types given in [Table 1]. [4],[5]
Table 1: Biopharmaceutical classification system of

Click here to view

Class 1 drugs dissolve rapidly in an aqueous environment and are rapidly transported over the absorbing membrane. From the point of view of a formulator, these types of drugs are perfect candidates and new strategies are not to be devised for them. For Class 2 drugs, dissolution becomes the rate-limiting phenomenon as they have good permeability characteristics. The in vivo absorption can be affected by several physiological factors, like the volume and pH of the intestinal juices, the presence of bile salts, food, enzymes and bacteria, motility of the gut, and the viscosity in the gut lumen. Class 3 drugs have permeation as the rate-limiting factor. The strategy for this class of drugs depends on the transport mechanism over the permeation membrane. For the Class 4 drugs, both dissolution and permeation are limiting and it is the most difficult task for a formulator to device a bioavailable dosage form of such a drug. Solid dispersion technology is mainly focused on improving the dissolution and absorption characteristics of Class 2 drugs with poor aqueous solubility. A pharmaceutical literature survey related to solid dispersions revealed that the dissolution behavior of a number of poorly water-soluble drugs have been altered with the help of solid dispersion techniques. The oral bioavailability of Class 2 drugs can be increased.

   Definition of Solid Dispersions Top

  • A dispersion of one or more ingredients in an inert carrier or matrix at solid state prepared by the melting (fusion), solvent, or melting solvent method. [6],[7]
  • A product formed by conversion of a fluid drug carrier combination to the solid state.
  • Solid dispersion refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug.

   Classification of Solid Dispersions Top

As the term solid dispersion technique signifies, a hydrophobic drug is molecularly dispersed in the polymers in its amorphous or crystalline state. Based on the molecular arrangement, six types of solid dispersions are identified [Table 2]. [7],[8],[9]
Table 2: Classification of solid dispersions[7],[8],[9]

Click here to view

Discussion on stability of solid dispersions

The dissolution characteristics and chemical integrity of a solid dispersion must remain unaltered during its shelf life period. For accomplishing optimum stability in a solid dispersion, the molecular mobility should be as low as possible. Mostly, solid dispersions are amorphous in nature and therefore most of them prove to be thermodynamically unstable. Nucleation and crystallization occur in solid dispersions containing crystalline particles. The better side of a crystalline matrix is that diffusion will be very slow and so degradation. Literature shows that such solid dispersions show poor dissolution characteristics on storage. The three important steps which finally results in the instability of a solid dispersion are diffusion, nucleation, and crystallization. [8],[10],[11] A, B, C, and D in [Figure 1], respectively represent molecularly dispersed drug, amorphous drug particles, partially crystalline particles, and crystalline drug particles.
Figure 1: The steps involved in the preparation of solid dispersions

Click here to view

Factors affecting the stability of solid dispersions

The physical state, molecular mobility, antiplasticization, drug-polymer ratio, molecular weight of the polymer, and drug-matrix interactions are the major factors that may affect the stability of solid dispersions. [11]

Physical state of solid dispersion

The crystalline state and the amorphous state are the two most important states of materials with respect to solid dispersions. [11],[12] The crystalline state is a thermodynamically stable form because the particles have less mobility and they have lesser energy. Amorphous materials are thermodynamically unstable and have a natural tendency to change to the crystalline state. [13] The two important physical states that can be identified in amorphous materials are glassy and rubbery state and their characteristics are compared in [Table 3]. [11]
Table 3: Characteristics of the two states of amorphous materials[11]

Click here to view

Molecular mobility in dispersion

Molecular mobility is one of the most important properties which determine the stability of a solid dispersion. It is related to macromolecular properties like viscosity, diffusion coefficient, and enthalpy Molecular mobility is quantified in terms of relaxation time (τ). [11],[12],[14]

Relaxation time

It is defined as the time required by a molecule or chain segment to diffuse across the matrix through a distance of one molecule or chain segment. Relaxation time varies with temperature. Typical relaxation times at glass transition temperature (T g ) are 100-200 seconds.

Glass transition temperature

It is defined as the temperature above which a material changes to a glass like consistency and share the properties of glass. [15]

In general, the glassy pharmaceutical solids should be expected to experience significant molecular mobility at temperatures up to 50°C below their glass transition temperature. [15]

Relaxation time at storage conditions indicates the shelf life period of a formulation. The extend of relaxation is mathematically represented with the help of Kohlrausch-Wiliams-Watts (Equation 1) here:

φ (t) =fraction of non relaxed material at time t

β = relaxation time distribution factor

Application of Kohlrausch-Wiliams-Watts equation [11]

  1. It represents parameters that are used to classify solid dispersions into different glasses
  2. It correlates temperature and relaxation time
  3. The prediction of shelf life using relaxation time and relaxation time distribution factor can be performed
  4. It also can be used to predict the viscosity changes in solid dispersions to some extent.
Literature reports the applicability of time temperature superposition (TTS) in studying the rheology of glasses and polymers. It has been reported that the processes involved in molecular relaxation or rearrangements in viscoelastic materials takes place at accelerated rates at higher temperatures. Moreover, there is a direct equivalency between time (the frequency of measurement) and temperature. [2]

Hence, the time over which these processes occur can be reduced by conducting the measurement at elevated temperatures and shifting the resultant data to lower temperatures. The result of this shifting is a "master curve" where the material property of interest at a specific end-use temperature can be predicted over a broad time scale. The amount of shifting along the horizontal (x-axis) in a typical TTS plot required to align the individual experimental data points into the master curve is generally described using one of two common theoretical models. The first of these models is the Williams-Landel-Ferry (WLF) (Equation 2): [16]

This equation is used for describing the behavior of fragile glasses. C 1 and C 2 are universal constants and T 0 is the reference temperature (in Kelvin), T is the measurement temperature (in Kelvin), and A t is the shift factor. The WLF equation is typically used to describe the time/temperature behavior of polymers in the glass transition region. The equation is based on the assumption that above the glass transition temperature, the fractional free volume increases linearly with respect to temperature. The model also assumes that as the free volume of the material increases, its viscosity rapidly decreases.

The other model commonly used is the Arrhenius equation (Equation 3) [17]

where E is the activation energy associated with the relaxation, R is the gas constant, T is the measurement temperature, T 0 is the reference temperature, and A t is the time-based shift factor. The Arrhenius equation is typically used to describe behavior outside the glass transition region but has also been used to obtain the activation energy associated with the glass transition. [17] Another model used in the rheological study of glassy solids is Vogel Tammann Fulcher (VTF) equation (Equation 4). [11]

It is used to model the behavior of amorphous solids. T 0 and D are universal constants. T 0 is the temperature at which either τ or η become infinite. D represents the strength parameter.

Classification of amorphous materials

The practical purpose definition of T g was used by Angell to classify amorphous materials as strong and fragile [Table 4] and plot the logarithms of viscosity and relaxation time as a function of (T g /T). [12],[18],[19] In such a plot as in [Figure 2], strong materials, i.e., materials that exhibit only small changes in the activation energy for flow with temperature, such as silica, have a nearly linear dependence on the inverse of the reduced temperature, whereas fragile materials deviate strongly from a linear dependence as the activation energies of fragile materials significantly change with temperature. However, this change is characteristic only for intermediate temperatures and the viscosity has Arrhenius type behavior asymptotically both at high and low temperatures. Within the low temperature, the activation energy of viscosity is high Q H , whereas at high temperatures the activation energy is low Q L . Doremus suggested to use the ratio (Equation 5).
Figure 2: Graphical representation of relationship between viscosity and relaxation time against temperature relative to TG

Click here to view
Table 4: Angell's classification of amorphous materials[11],[18]

Click here to view

as a fragility criterion. [12],[20],[21] The higher the value of R D , the more fragile the material. The fragility of amorphous materials numerically characterized by the Doremus' fragility ratio classifies amorphous materials as strong if they have R D < 2, and fragile materials if they have R D ≥ 2. [12]


It can be defined as a stabilization mechanism for a solid dispersion in which a matrix with higher glass transition temperature (T g ) is used which reduces the molecularly mobility of the drug and produces a highly stable solid dispersion. Many matrices are hygroscopic and water will be homogenously distributed in the solid dispersion. Water has a very low T g of 135(K) and it obviously reduces the T g of the solid dispersion considerably which leads to higher molecular mobility and material will be devitrified. The T g of such solid dispersions can be predicted with the help of Gordon-Taylor equation (Equation 6); [11],[22]

T g, MIX = T g of solid dispersion.

T g, D = T g of drug.

T g, C = T g of matrix

W D = weight fraction of drug

The constant K is given by the Simha-Boyer rule (Equation 7) as [22]

ρD = Density of drug

ρC = Density of matrix

Drug-polymer ratio [11]

When the drug has a lower T g than the matrix, a higher drug content decreases the T g of the solid dispersion and chances of phase separation are increased. Increasing the drug load deteriorates physical stability by altering the T g of homogenous solid dispersions and also by facilitating crystallization. Increasing the drug load improves physical stability by reducing the plasticizing effect of water and also inhibits phase separation by preventing matrix crystallization. Effects of changing the drug matrix ratio are summarized in [Table 5].
Table 5: Effects of drug– matrix ratio

Click here to view

Molecular weight of polymer

Development of a stable solid dispersion depends on the minimization of its molecular mobility, and for this purpose matrices with a higher T g are preferred. [11] A high molecular weight matrix has smaller free volume and thus molecular motions are restricted in such a system. Fox-Flory equation (Equation 8) gives the relation between T g and molecular weight: [23]

Tg = T g at infinite chain length

K = constant depending on monomer geometry

DP = degree of polymerization

Drug-matrix interactions

Drug-matrix interactions determine the physical stability of solid dispersions of solid dispersions during storage. The extend and type of interactions govern the miscibility during fusion, dissolution in common solvent, phase separation, and dissolution of the solid dosage form. Drug-matrix interactions contribute to an increase of T g than predicted by the Gordon-Taylor equation. [11] Strong interactions present during complex formation increase the T g and hence increased physical stability.


  1. Hydrogen bonding of drugs with poly vinyl pyrrolidone (PVP) [24],[25]
  2. Photostability of nifidipine and chlorpromazine hydrochloride is increased when incorporated in cyclodextrin cavity. [26],[27]

   Preparation of Solid Dispersions Top

Many preparation techniques are currently available for solid dispersions. Phase separation and demixing are the most important problems associated with preparation of solid dispersions. [8] As reported, rapid cooling procedures can reduce the extent of phase separation. The different techniques are as follows:

  • Fusion/melting method
  • Solvent evaporation method
  • Hot melt extrusion method
  • Supercritical fluid method
  • Miscellaneous method
Fusion/melting method

Fusion method is one of the earliest techniques used for preparation of solid dispersions. First, pharmaceutically applicable solid dispersion was prepared by using this method. Sekiguchi and Obi prepared solid dispersions of sulfathiazole in carriers such as ascorbic acid, acetamide, nicotinamide, nicotinic acid, succinimide, and urea by melting various drug-carrier mixtures. [8],[28],[29],[30] It was a eutectic mixture of sulphathizole and urea, which was fused and later cooled to get the final dispersion. The eutectic composition was chosen in order to obtain simultaneous crystallization of drug and matrix during cooling. Polyethylene glycol (PEG) is the hydrophilic polymer commonly used for preparation of solid dispersions. The polymers used generally are

  1. Polyethylene glycol (PEG) [MP: 70°C]: Type 3 solid dispersions are produced
  2. Poly vinyl pyrrolidone (PVP) [MP: 169°C]: Type 5 and 6 solid dispersions are obtained.

  • The method can only be applied when drug and matrix are compatible and when they mix well at the heating temperature
  • Drug and matrix being incompatible results in homogeneous solid dispersions due to formation of two liquid phases
  • During cooling, the drug-matrix miscibility changes which eventually results in phase separation
  • Degradation of the drug and or matrix can occur during heating to temperatures necessary to fuse matrix and drug.
Solvent evaporation method

The two important steps are

  1. A solution containing the matrix and the drug is prepared by proper molecular level mixing with the solvent.
  2. Removal of the solvent. [11],[28],[31]
As the drug and matrix differ comparatively in their polarities, molecular level mixing in a particular solvent becomes very difficult. Another problem is the dispersal of drug and polymer in the finest state as possible to reduce the particle size of the solid dispersion. Use of solubilizers like cyclodextrins and surfactants like tweens are an important strategy to make the drug soluble. [32] The most efficient strategy to increase aqueous solubility of drug is the engaging of a mixture of solvents, for example, water-ethanol, dichloromethane-ethanol.

One of the most important problems associated with the solvent method is the chances of phase separation while solvent removal. Drying at higher temperature speeds up the process and reduces the time available for phase separation. But at higher temperatures the molecular mobility of drug and matrix remains high favoring phase separation. The drying techniques used are summarized in [Table 6] and an illustration of a spray drying technique is given in [Figure 3].
Figure 3: An illustration of a spray drying technique

Click here to view
Table 6: Drying techniques used in solvent evaporation method

Click here to view

Hot melt extrusion method

Hot melt extrusion technique was introduced into the pharmaceutical industry as a manufacturing tool around 1970s. [33],[34],[35],[36] The basic principle of this technology is similar to that of fusion method except for the employing of extruder for high shear mixing. Literature reports melt extrusion of immiscible components leads to formation of solid dispersion of amorphous drug in a crystalline excipient matrix. The Leistritz twin screw extruder is shown in [Figure 4]. [37]
Figure 4: The leistritz twin screw extruder

Click here to view


  • Single step preparation of solid dispersions [11]
  • Low temperature and shorter residence time of drug-carrier matrix (<2 min)
  • Potential to shape the heated drug-matrix mixture into implants, ophthalmic inserts, or oral dosage forms
  • Absence of organic solvents and continuous operation
  • Greater control on operation parameters and larger scale up possibilities.

  • Miscibility of drug and matrix is the major risk factor
  • High shear forces resulting in high local temperatures in the extruder be a problem for heat-sensitive materials.
Supercritical fluid methods

This technology has been introduced in the late 1980s and early 1990s, and experimental proofs of concept are abundant in the scientific literature for a plethora of model compounds from very different areas such as drugs and pharmaceutical compounds, polymers and biopolymers, explosives and energy materials, superconductors and catalyst precursor dyes, and biomolecules such as proteins and peptides. [38] From the very beginning of supercritical fluid particle generation research, the formation of biocompatible polymer and drug-loaded biopolymer microparticles for pharmaceutical applications has been studied intensively by a number of research groups. [39] In this method, carbon dioxide (CO 2 ) is used either as a solvent or as antisolvent. Super critical CO 2 is used to dissolve the drug and matrix and sprayed into an adiabatic expansion vessel and the mixture is cooled rapidly. It is usually referred as the solvent free method or Rapid Expansion of Super Critical Solution (RESS). The applicability of this method is very limited because of the solubility of most pharmaceutical compounds in CO 2 is very less. A schematic representation of the processes involved in supercritical fluid technology is shown in [Figure 5]. There are many precipitation methods which come under this class. The two reported precipitation methods are

  • Gas antisolvent technique (GAS) or precipitation from gas saturated solution (PGSS)
  • Precipitation with compressed antisolvent (PCA)
Figure 5: A schematic representation of the processes involved in supercritical fluid technology

Click here to view
Gas antisolvent technique or precipitation from gas saturated solution

solution is brought into contact with compressed CO 2. The conditions are chosen such that CO 2 is completely miscible with the solution under supercritical conditions, whereas drug and matrix will precipitate upon expansion of solution. When the volume of solution expands, the solvent strength decreases. This results in precipitation of the matrix and drug. PEG is usually used as the matrix in this method. [40],[41]

Precipitation with compressed antisolvent

It involves spraying of a solution containing drug and matrix through a nozzle into a vessel that contains a liquid or supercritical antisolvent. The supercritical antisolvent rapidly penetrates into the droplets, in which drug and matrix become supersaturated, crystallize, and form particles. Examples of PCA are supercritical antisolvent (SAS) or aerosol solvent extraction system (ASES) and solution enhanced dispersion by supercritical fluids (SEDS). [40],[41]

Miscellaneous methods

Evaporative precipitation into aqueous solutions

is reportedly used to coat a colloidal suspension of carbamazepine with block copolymers as stabilizing surfactants. A solution of drug in dichloromethane was sprayed in an aqueous solution containing polymeric surfactants as stabilizers. The obtained colloidal suspension was spray dried, freeze dried, or spray freeze dried, resulting in solid dispersions of types 4 and 5. [8],[42]

Supercritical fluid impregnation

involves dissolving the drug in a supercritical fluid and exposed to the solid matrix that swells and absorbs the supercritical solution. The diffusion process is controlled by varying the temperature and pressure. The process was reported with poly methyl methacrylate. [8],[11]

Electrostatic spinning process

It involves the drug-matrix solution to be pumped through an orifice and then subjected to an electrical field to form fibers of micro- or nanoscale. The fiber diameter can be adjusted by surface tension, electrical field, and dielectric constant. [8],[11]

   Conclusion Top

The commercial viability of solid dispersion technology is still not cent percent, but it is a promising technology in advanced drug delivery systems. We have summarized the already reported literatures regarding the formulation of solid dispersion of different drugs in [Table 7]. Stability, reproducibility, and scale up problems hamper the commercialization of this technique. Availability of new surface active and self-emulsifying carriers extends rays of hope in increasing the commercial feasibility of the technique. Products developed using the surface active carrier technology is available in market. Major focus of future research will be identification of new surface-active carriers and self-emulsifying carriers for solid dispersion. Research should also be directed toward identification of vehicles or excipients that would retard or prevent crystallization of drugs from supersaturated systems.
Table 7: Review of already reported solid dispersions

Click here to view

   References Top

1.Pharmapedia - the free pharmaceutical encyclopedia [INTERNET]. Oral delivery of poorly soluble drugs .[updated 2006 Aug 12;]. Available from: [Last cited on 2007 Feb 23].  Back to cited text no. 1
2.Karanth H, Shenoy VS, Murthy RR. Industrially feasible alternative approaches in the manufacture of solid dispersions: A technical report. AAPS Pharm Sci Tech 2006;7:E1-8.  Back to cited text no. 2
3.Chaudhari P. Current trends in solid dispersions techniques. [INTERNET]. 2006 May 17; 4(3): [about 11 screens]. Available from: [Last cited on 2010 Dec 6].  Back to cited text no. 3
4.Chavda HV, Patel CN, Anand IS. Biopharmaceutics classification system. Syst Rev Pharm 2010;1:62-9.  Back to cited text no. 4
  Medknow Journal  
5.Amidon GL, Lennernas H, Shah VP, Crison JR. Theoretical basis for a biopharmaceutical drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1999;12:413-20.  Back to cited text no. 5
6.Tiwari R, Tiwari G, Srivastava B, Rai AK. Solid Dispersions: An overview to modify bioavailability of poorly water soluble drugs. Int J Pharm Tech Res 2009;1:1338-49.  Back to cited text no. 6
7.Chiou WL, Rielman S. Pharmaceutical application of solid dispersion system. J Pharm Sci 1971;60:1281-302.  Back to cited text no. 7
8.Dhirendra K, Lewis S, Udupa N, Atin K. Solid dispersions: A review. Pak J Pharm Sci 2009;22:234-46.  Back to cited text no. 8
9.Swarbrick J. Encyclopedia of Pharmaceutical Technology, 3 rd Ed, 2006. p.775-7.  Back to cited text no. 9
10.Habib MJ. Pharmaceutical Solid Dispersion Technology.1 st ed. Lancaster: Technomic Pub. Co; 2000. p. 7-26.  Back to cited text no. 10
11.Drooge DJ. Combining the Incompatible: Inulin glass dispersions for fast dissolution, stabilization and formulation of lipophilic drugs [Ph.D. Thesis] [internet].[ Leiden(The Netherlands)]:University of Groningen; 2006. Chapter 1, Introduction: Production, stability, and dissolution of solid dispersions to improve the bioavailability of class II lipophilic drugs: 7-37. Available from: [Last cited on 2011 Oct 22].  Back to cited text no. 11
12.Ojovan MI. Configurons: Thermodynamic parameters and symmetry changes at glass transition. Entropy 2008;10:334-64.  Back to cited text no. 12
13.Hilden LR, Morris KR. Physics of amorphous solids. J Pharm Sci 2004;93:3-12.  Back to cited text no. 13
14.Angell CA, Ngai KL, McKenna GB, McMillan PF, Martin SW. Relaxation in glass forming liquids and amorphous solids. App Phys Rev 2000;88:3113-57.  Back to cited text no. 14
15.Hancock BC, Shamblin SL, Zografi G. Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures. Pharm Res1995;12:799-806.  Back to cited text no. 15
16.Williams ML, Landel RF, Ferry JD. The temperature dependence of relaxation mechanisms in amorphous polymers and other glass-forming liquids. J Am Chem Soc 1955;77:3701.  Back to cited text no. 16
17.Application of time temperature superposition principles to rheology [INTERNET]. New Castle: TA Instruments Inc. c2011: [about 6 screens]. Available from: [Last cited on 2011 Apr 25].  Back to cited text no. 17
18.Angel CA. Perspective on the glass transition. J Phys Chem Solids 1988;49:863-71.   Back to cited text no. 18
19.Martinez LM, Angel CA. A thermodynamic connection to the fragility of glass forming liquids. Nature 2001;410:663-7.   Back to cited text no. 19
20.Doremus RH. Melt viscosities of silicate glasses. Am Ceram Soc Bull 2003;82:59-63.   Back to cited text no. 20
21.Doremus RH. Viscosity of silica. J Appl Phys 2002;92:7619-29.   Back to cited text no. 21
22.Blasi P Schoubben A, Giovagnoli S, Perioli L, Ricci M, Rossi C. Ketoprofen Poly(lactide-co-glycolide) Physical Interaction. AAPS Pharm Sci Tech 2007;8:Article 37.  Back to cited text no. 22
23.Tang WT, Hadziioannou G, Smith BA, Frank CW. Synthesis and characterization of T g for pyrene end-labelled polystyrene having no ester linkages. Polymer 1988;29:1718-23.   Back to cited text no. 23
24.Papageorgiou GZ, Papadimitriou S, Karavas E, Georgarakis E, Docosli A, Bikiari D. Improvement in chemical and physical stability of fluvastatin drug through hydrogen bonding interactions with different polymer matrices. Curr Drug Deliv 2009;6:101-12.  Back to cited text no. 24
25.Wen H, Morris KR, Park K. Study on the interactions between polyvinylpyrrolidone (PVP) and acetaminophen crystals: Partial dissolution pattern change. J Pharm Sci 2005;94:216674.   Back to cited text no. 25
26.Glass BD, Brown ME, Daya S, Worthington MS, Drummond P, Antunes E, et al. Influence of cyclodextrins on the photostability of selected drug molecules in solution and the solid-state. Int J Photoenergy 2003;1:205-11.  Back to cited text no. 26
27.Ammar HO, Ghorab M, El nahhas SA, Omar SM, Ghorab MM. Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation (Chlorpromazine hydrochloride). Pharmazie 1995;50:805-8.  Back to cited text no. 27
28.Singh MC, Sayyad AB, Sawant SD. Review on various techniques of solubility enhancement of poorly soluble drugs with special emphasis on solid dispersion. J Pharm Res 2010;3:2494-501.  Back to cited text no. 28
29.Sethia S, SquillanteE. Solid Dispersions: Revival with greater possibilities and applications in oral drug delivery. Crit Rev Ther Drug Carrier Syst 2003;20:217-49.  Back to cited text no. 29
30.Sekiguchi K, Obi N. Studies on Absorption of eutectic mixture II. Absorption of fused conglomerates of chloramphenicol and urea in rabbits. Chem Pharm Bull 1964;12:134-44.  Back to cited text no. 30
31.Goldberg A, Gibaldi M, Kanig JL. Increasing dissolution rates and gastrointestinal absorption of drugs via solid solutions and eutectic mixtures III - experimental evaluation of griseofulvin- succinic acid solid solution. J Pharm Sci 1966;55:487-92.  Back to cited text no. 31
32.Serajuddin A. solid dispersion technique. J Pharm Sci 1999;88:891-900.  Back to cited text no. 32
33.Narang A, Shrivastava A. Melt extrusion solid dispersion technique. Drug Dev Ind Pharm 2002;26:111-5.  Back to cited text no. 33
34.Laxman J, Cao Y, Kowlaski J. Application of melt extrusion in development of Physically and chemically stable high energy amorphous solid dispersion of poorly water soluble drugs. Mol Pharmaceutics 2008;5:994-1002.  Back to cited text no. 34
35.Breitenbach J. Melt extrusion: From process to drug delivery technology. Eur J Pharm Biopharm 2002;54:107-17.  Back to cited text no. 35
36.Chokshi R, Hossein Z. Hot -Melt Extrusion Technique: A Review. Int J Pharm Res 2004;3:3-16.  Back to cited text no. 36
37. Pressbox: Rottendorf Pharma GmbH [Internet]. Hot-melt extrusion - a pioneering technology at Rottendorf Pharma. Pressbox. c2002-2011. Available from: [Last cited on 2011 Apr 26].  Back to cited text no. 37
38.Muhrer G, Meier U, Fusaro F, Albano S, Mazzotti M. Use of compressed gas precipitation to enhance the dissolution behavior of a poorly water-soluble drug: Generation of drug microparticles and drug-polymer solid dispersions. Int J Pharm 2006;308;69-83.  Back to cited text no. 38
39.Ghaste RP, Chougule DD, Shah RR, Ghodake DS. Solid Dispersions: An Overview. [Internet]. 2009;7(5):[about 11 screens]. Available from: [Last cited on 2010 Dec 9].  Back to cited text no. 39
40.Shariati A, Peters CJ. Recent developments in particle design using supercritical fluids. Curr Opin Solid State Mater Sci 2003;7:371-83.  Back to cited text no. 40
41.Marentis R. Particle formation using supercritical carbondioxide. [Internet]. Allentown: Supercritical technology Consultants. [about 6 p.]. Available from: [Last cited on 2011 May 13].  Back to cited text no. 41
42.Sarkari M, Brown J, Chen X, Swinnea S, Williams RO, Johnston KP. Enhanced drug dissolution using evaporative precipitation into aqueous solution. Int J Pharm 2002;243:17-31.   Back to cited text no. 42
43.Aejaz A, Azmail K, Sanaullah S, Mohsin AA. Formulation and in vitro evaluation of aceclofenac solid dispersion incorporated gels. Int J Appl Pharm 2010;2:7-12.  Back to cited text no. 43
44.Shrivastava AR, Ursekar B, Kapadia CJ. Design, optimization, preparation and evaluation of dispersion granules of valsartan and formulation into tablets. Curr Drug Deliv 2009;6:28-37.  Back to cited text no. 44
45.Yunzhe S, Rui Y, Wenliang Z, Xing T. Nimodipine semi-solid capsules containing solid dispersion for improving dissolution. Int J Pharm 2008;359:144- 9.  Back to cited text no. 45
46.Malviya R, Srivastava P, Bansal M, Sharma PK. Improvement of dissolution behavior of paracetamol using solid dispersion technique. Int J Pharm Sci Res 2010;1:95-9.  Back to cited text no. 46
47.Papageorgiou GZ, Papadimitriou S, Karavas E, Georgarakis E, Docoslis A, Bikiaris D. Improvement in chemical and physical stability of fluvastatin drug through hydrogen bonding interactions with different polymer matrices. Curr Drug Deliv 2009;6:101-12.  Back to cited text no. 47
48.Rao BA, Shivalingam MR, Reddy YV, Rao S, Rajesh K, Sunitha N. Formulation and evaluation of aceclofenac solid dispersions for dissolution rate enhancement. Int J Pharm Sci Drug Res 2010;2:146-50.  Back to cited text no. 48
49.Sachan NK, Pushkar S, Solanki SS, Bhatere DS. Enhancement of solubility of acyclovir by solid dispersion and inclusion complexation methods. World Appl Sci J 2010;11:857-64.  Back to cited text no. 49
50.Chaulang G, Patil K, Ghodke D, Khan S, Yeole P. Preparation and characterization of solid dispersion tablet of furosemide with crospovidone. Res J Pham Tech 2008;1:386-9.  Back to cited text no. 50
51.Ye G, Wang S, Heng PW, Chen L, Wang C. Development and optimization of solid dispersion containing pellets of itraconazole prepared by high shear pelletization. Int J Pharm 2007;337:80-7.  Back to cited text no. 51
52.Boghra RJ, Kothawade PC, Belgamwar VS, Nerkar PP, Tekade AR, Surana SJ. Solubility, dissolution rate and bioavailability enhancement of irbesartan by solid dispersion technique. Chem Pharm Bull 2011;59:438-41.  Back to cited text no. 52
53.Markoin W, Duda H. Influence of selected auxillary susbstances on some physicochemical properties of solid dispersions containing magnesium salts. Acta Poloniae pharmaceutica Drug Res 2004;61:97-103.  Back to cited text no. 53
54.Padma Priya S, Rajendran NN, Lakshmi PK, Umadevi SK, Vaijayanthy V, Kausalya J, et al. A novel captopril hydrochlorothiazide solid dispersion. Int J Pharm Pharm 2010;2:30-2.  Back to cited text no. 54
55.Coppens KA, Hall MJ, Koblinski BD, Larsen PS, Read MD, Shrestha U. Controlled release of amorphous solid dispersion utilizing hot melt extrusion [Internet]. Poster presented at the 2009 Annual meeting and exposition of the American association of pharmaceutical scientists; 2009 Nov 8-12; Los Angeles, California. The Dow Chemical Company: USA; 2009. p.1-5: Available from: [Last cited on 2010 May 10].  Back to cited text no. 55
56.Swain SK, Patra N, Sruti J, Rao ME. Design and evaluation of sustained release solid dispersions of verapamil hydrochloride. Int J Pharm Sci Nanotech [Internet]. 2011;3(4): [about 1 p. ]. Available from: [Last cited on 2002 Aug 12].  Back to cited text no. 56
57.Biswal S, Sahoo J, Murthy PN. Characterisation of Gliclazide-PEG 8000 Solid Dispersions. Trop J Pharm Res 2009;8:417-24.  Back to cited text no. 57
58.Patil MP, Gaikwad NJ. Preparation and characterization of gliclazide-polyethylene glycol 4000 solid dispersions. Acta Pharma 2009;59:57-65.  Back to cited text no. 58
59.Suhagia BN, Patel HM, Shah SA, Rathod I, Parmar VK. Preparation and characterization of etoricoxib-polyethylene glycol 4000 plus polyvinylpyrrolidone K30 solid dispersions. Acta Pharma 2006;56:285-98.  Back to cited text no. 59
60.Patel T, Patel LD, Patel T, Makwana S, Patel T. Enhancement of dissolution of Fenofibrate by Solid dispersion Technique. Int J Res Pharm Sci 2010;1:127-32.  Back to cited text no. 60
61.Badry ME, Fetih G, Fathy M. Improvement of solubility and dissolution rate of indomethacin by solid dispersions in Gelucire 50/13 and PEG 4000. Saudi Pharm J 2009;17:219-30.  Back to cited text no. 61
62.Margarit MV, Marin MT, Contreras MD. Solubility of solid dispersions of pizotifen malate and povidone. Drug Dev Ind Pharm 2001;27:517-22.  Back to cited text no. 62
63.Charumanee S, Okonoki S, Sirithunyalug J. Improvement of dissolution rate of piroxicam by surface solid dispersion [Internet].: [about 1 p.]. Available from: [Last cited on 2011 Apr 12].  Back to cited text no. 63
64.Valizadeh H, Nokhodchi A, Qarakhani N, Zakeri-Milani P, Azarmi S, Hassanzadeh D, et al. Physicochemical characterization of solid dispersions of indomethacin with PEG 6000, Myrj 52, lactose, sorbitol, dextrin, and Eudragit E100. Drug Dev Ind Pharm 2004;30:303-17.  Back to cited text no. 64
65.Hasan S, Ali J, Baboota S, Ali M. Comparative analysis of Acyclovir-PEG solid dispersion for bioavailability enhancement. [Internet].: [about 1 p.]. Available from: [Last cited on 2011 Apr 26].  Back to cited text no. 65
66.Al-Saidan SM, Krishnaiah YS. Preparation and characterisation of glimepiride solid dispersions by powder x-ray diffraction and differential scanning calorimetry. [Internet].: [about 1 p.]. Available from: [Last cited on 2011 Apr 26].  Back to cited text no. 66
67.Balata G, Mahdi M, Bakera RA. Improvement of solubility and dissolution properties of ketoconazole by solid dispersions and inclusion complexes. Asian J Pharm Sci 2010;5:1-12.  Back to cited text no. 67
68.Rathinaraj BS, Rajveer C, Choudhury PK, Sheshrao BG, Shinde GV. Studies on dissolution behaviour of sustained release solid dispersions of nimodipine. Int J Pharm Sci Rev Res 2010;3:77-82.  Back to cited text no. 68
69.Prasad KA, Narayanan N, Rajaakshmi G. Preparation and evaluation of solid dispersion of terbinafine hydrochloride. Int J Pharm Sci Rev Res 2010;3:130-4.  Back to cited text no. 69
70.Nokhodchi A, Talari R, Valizadeh H, Jalali MB. An investigation on the solid dispersions of chlordiazepoxide. Int J Biomed Sci 2007;3:211-7.  Back to cited text no. 70
71.Gill B, Kaur T, Gupta GD. Formulation and evaluation of glimepiride solid dispersion tablets. Asian J Pharm 2010;4:212-8.  Back to cited text no. 71
  Medknow Journal  
72.Khan A, Sanaullah S, Ahmed ML. Ahmed A. In vivo efficacy study of aceclofenac solid dispersion incorporated gels for transdermal delivery on rats. Asian J Exp Biol Sci 2010;1:602-5.  Back to cited text no. 72
73.Patel MP, Gaikwad NJ. Characterization of gliclazide-polyethylene glycol solid dispersion and its effect on dissolution. Braz J Pharm Sci 2011;47:161-6.  Back to cited text no. 73
74.Ren F, Jing Q, Tang Y, Shen Y, Chen J, Gao F, et al. Characteristics of bicalutamide solid dispersions and improvement of the dissolution. Drug Dev Ind Pharm 2006;32:967-72.  Back to cited text no. 74
75.Khougaz K, Clas SD. Crystallization inhibition in solid dispersions of MK-0591 and poly (vinylpyrrolidone) polymers. J Pharm Sci 2000;89:1325-34.   Back to cited text no. 75
76.Shahroodi AB, Nassab PR, Revesz PS. Preparation of a solid dispersion by a dropping methodto improve the rate of dissolution of meloxicam. Drug Dev Ind Pharm 2008;34:781-8.   Back to cited text no. 76
77.Samy AM, Marzouk MA, Ammar AA, ahmed MK. Enhancement of the dissolution profi le of allopurinol by a solid dispersion technique. Drug Discov Ther 2010;4:77-84.  Back to cited text no. 77
78.Dangprasirt P, Ritthidej GC. Development of diclofenac sodium controlled release solid dispersions by spray drying using optimization strategy I powder formulation. Drug Dev Ind Pharm 1995;21:2323-37.  Back to cited text no. 78
79.García Rodriguez JJ, de la Torre-Iglesias PM, Vegas Sánchez MC, Torrado Durán S, Bolás Fernández F, Santiago ST. Changed crystallinity of mebendazole solid dispersion: Improved anthelmintic activity. Int J Pharm 2011;403:23-8.  Back to cited text no. 79
80.Okonogi S, Puttipipatkhachorn S. Dissolution improvement of high drug-loaded solid dispersion. AAPS Pharm Sci Tech 2006;7: Article 52.   Back to cited text no. 80
81.Sukhdevbhai BS. Controlled release solid dispersions of indomethacin for direct use in the preparation of multiple strengths solid dosage forms. [dissertation].[Internet]. The Brooklyn Center: Long Island University; 2008. Available from: d=79356andRQT=309andVName=PQD. [Last cited on 2011 Apr 25].  Back to cited text no. 81
82.Punitha K, Kumari DC, Kumar VV, Kumar SS. Enhancement of solubility of Rosiglitazone through solid dispersion technique: in-vitro and in-vivo permeation study analysis. Der Pharma Chemica 2010;2:190-200.   Back to cited text no. 82
83.Mandal D, Ojha PB, Nandy BC, Ghosh SK. Effect of carriers on solid dispersions of simvastatin (sim): physico-chemical characterizations and dissolution studies. Der Pharma Chemica 2010;2:47-56.   Back to cited text no. 83
84.Tiwari R, Srivastava B, Tiwari G, Rai A. Extended release promethazine HCl using acrylic polymers by freeze-drying and spray-drying techniques: formulation considerations. Braz J Pharm Sci 2009;5:161-6.829-40.  Back to cited text no. 84
85.Biswal S, Pasa GS, Sahoo J, Murthy PN. An approach for improvement of the dissolution rate of gliclazide. 2009 Nov. In: Dissolution Technologies [Internet]. Yorkridge Trail: Dissolution Technologies, Inc. c1998-2010:15-20. Available from: [Last cited on 2011 May 13].  Back to cited text no. 85
86.Pandya VM, Patel DJ, Patel JK, Patel RP. Formulation, characterization, and optimization of fast-dissolve tablets containing celecoxib solid dispersion. 2009 Nov. In: Dissolution Technologies [Internet]. Yorkridge Trail: Dissolution Technologies, Inc. c1998-2010:22-7. Available from: [Last cited on 2011 May 16].  Back to cited text no. 86
87.Uddin R, Saffoon N, Huda NH, Jhanker YM, Effect of water soluble polymers on dissolution enhancement of ibuprofen solid dispersion prepared by fusion method. S J Pharm Sci 2010;3:63-7.  Back to cited text no. 87
88.Shaikh SM, Avachat AM. Enhancement of solubility and permeability of candesartan cilexetil by using different pharmaceutical interventions. Curr Drug Deliv 2011;8:346-53.  Back to cited text no. 88
89.Bansal SS, Kaushal AM, Bansal AK. Enthalpy relaxation studies of two structurally related amorphous drugs and their binary dispersions. Drug Dev Ind Pharm 2010;36:1271-80.   Back to cited text no. 89
90.Yoshihashi Y, Iijima H, Yonemochi E, Terada K. Estimation of physical stability of amorphous solid dispersion using differential scanning calorimetry. J Therm Anal Calorim 2006;85:689-92.   Back to cited text no. 90
91.Wu K, Li J, Wang W, Winstead DA. Formation and characterization of solid dispersions of piroxicam and polyvinylpyrrolidone using spray drying and precipitation with compressed antisolvent. J Pharm Sci 2009;98:2422-31.  Back to cited text no. 91
92.Jyothibasu T, Reddy YV, Rao AB, Tejaswi V, Nagaanusha D. Formulation and evaluation of solid dispersions of glipizide for dissolution rate enhancement. Int J Pharm Res Dev 2011;39:231-9.  Back to cited text no. 92


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Definition of So...
    Classification o...
    Preparation of S...
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded680    
    Comments [Add]    

Recommend this journal