Solid Dispersions: A Review


Punitha S*, Srinivasa Reddy G, Srikrishna T and Lakshman Kumar M

Department Of Pharmaceutics, PRIST University, East Campus, Thanjavur- 613 401, India

*Corresponding Author E-mail:



Solid dispersion can be defined as “The dispersion of one or more active ingredients in an inert carrier or matrix at solid state”. Solid dispersions are prepared with an aim to improve the solubility and dissolution rate. Polyethylene Glycols (PEG4000, PEG6000and PEG8000), Polyvinyl pyrrolidone (PVP) used as polymers in the preparation of solid dispersions. Chloroform, Ethanol, Methanol is used as the solvents. The method of preparation of solid dispersions include Fusion method, hot melt extrusion, Solvent evaporation method, super critical fluid method, Dielectrostatic spinning process. Solid dispersions are divided into six types based on their molecular arrangement. They are Eutectics (crystalline drug in crystalline matrix),Amorphous precipitations in crystalline matrix (crystalline drug in amorphous matrix),Solid solutions (crystalline drug molecularly dispersed in matrix),Glass suspensions (crystalline drug in amorphous matrix),Glass suspensions (amorphous drug in amorphous matrix),Glass solutions (amorphous drug molecularly dispersed in matrix).Thin Layer Chromatography and Infra Red spectral analysis confirms the absence of interaction between the drug and the carriers. A marked improvement in the dissolution rate was observed in all the solid dispersions compared with the pure drug.900ml of 0.1M pH 7.4 phosphate buffer used as dissolution medium. The stirrer is adjusted to 75 rpm at 37oC and absorbance is measured by using UV-vis spectrophotometer.


KEYWORDS: Solid dispersions, Solvent evaporation method, Fusion method, Super critical fluid method, hot melt extrusion, polyvinyl pyrrolidone (PVP), Polyethylene Glycols (PEG4000, PEG6000and PEG8000), chloroform, dichloro ethane.




The progress in treatment of diseases has been evident with an upsurge in development of new drugs. An estimated 40% of these drugs are poorly water soluble. Although most of the drugs have encouraging experimental data obtained in vitro, the in vivo results have been disappointing1.

The attributes include

1.        Poor absorption, rapid degradation, and lamination (peptides and protein) resulting in insufficient concentration.

2.        Drug distribution to other tissues with high drug toxicities (anticancer drugs).

3.        Fluctuations in plasma levels owing to unpredictable bioavailability2.

The enhancement of oral bioavailability of such poorly water-soluble drugs remains one of the most challenging aspects of drug development. The development of solid dispersions as a practically viable method to enhance bioavailability of poorly water-soluble drugs overcame the limitations of previous approaches such as salt formation, solubilization by co solvents, and particle size reduction3.


Studies revealed that drugs in solid dispersion need not necessarily exist in the micronized state. A fraction of the drug might molecularly disperse in the matrix, thereby forming a solid dispersion4. When the solid dispersion is exposed to aqueous media, the carrier dissolves and the drug releases as fine colloidal particles. The resulting enhanced surface area produces higher dissolution rate and bioavailability of poorly water-soluble drugs. In addition, in solid dispersions, a portion of drug dissolves immediately to saturate the gastrointestinal tract fluid, and excess drug precipitates as fine colloidal particles or oily globules of submicron size5. In spite of these advantages, only two products have been marketed since the development of this technology 4 decades ago. The limitations of this technology have been a drawback for the commercialization of solid dispersions6. The limitations include

1.        Laborious and expensive methods of preparation,

2.        Reproducibility of physicochemical characteristics,

3.        Difficulty in incorporating into formulation of dosage forms,

4.        Scale-up of manufacturing process, and

5.        Stability of the drug and vehicle.

Various methods have been tried to overcome the limitations and make the preparation more practically feasible while, at the same time, retaining both the physicochemical and bioavailability enhancing properties of solid dispersions7. Some of the suggested approaches to overcome the  aforementioned problems and lead to industrial scale production are reviewed in the Alternative Strategies include spraying on sugar beads using a fluidized bed coating system and direct capsule filling8.



Solid dispersion refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. The matrix can be either crystalline or amorphous. The drug can be dispersed molecularly, in amorphous particles (clusters) or in crystalline particles9.


Types of solid dispersions10:

1.        Dispersion type

2.        Amorphous precipitations in crystalline matrix

3.        Solid solutions

a) Continuous solid solutions

b) Discontinuous solid solutions

c) Substitutional solid solutions

d) Interstitial solid solutions

4. Glass suspension



Various methods of preparation of solid dispersions are mentioned below. These methods deal with the challenge of mixing a matrix and a drug.

1.        Fusion method

2.        Hot melt extrusion

3.        Solvent evaporation  method

4.        Supercritical fluid method

5.        Other methods


Fusion method:

The fusion method is sometimes referred to as the melt method, which is correct only when the starting materials are crystalline. The first solid dispersions created for pharmaceutical applications were prepared by the fusion method. The dispersion consisted of sulfathiazole and urea as a matrix which were melted using a physical mixture at the eutectic composition, followed by a cooling step12. The eutectic composition was chosen to obtain simultaneous crystallization of drug and matrix during cooling. This procedure resulted in solid dispersions of amorphous precipitations in crystalline matrix. Polyethylene glycol (PEG) is a hydrophilic polymer often used to prepare solid dispersions with the fusion method. Another polymer frequently applied as a matrix in the fusion method is polyvinyl pyrollidone (PVP).The drug has to fuse with or dissolve in the rubbery matrix, which is subsequently cooled to vitrify the solid dispersion. When PVP is used as matrix, solid dispersions of amorphous precipitation in crystalline matrix are obtained. The mode of incorporation of the drug depends on the PVP-drug miscibility and the preparation procedure. Grinding is required to obtain the solid dispersion as powder that is easy to handle.


Hot melt extrusion:

Hot melt extrusion is essentially the same as the fusion method except that intense mixing of the components is induced by the extruder. When compared to melting in a vessel, the product stability and dissolution are similar, but melt extrusion offers the potential to shape the heated drug-matrix mixture into implants, ophthalmic inserts, or oral dosage forms13.


Solvent evaporation method:

The solvent evaporation method includes 2 steps the first step in the solvent method is the preparation of a solution containing both matrix material and drug. The second step involves the removal of solvent(s) resulting in formation of a solid dispersion14. Solubilisers like cyclodextrins or surfactants like Tween80 increase the aqueous solubility of the drug. Chloroform or dichloromethane have been used as solvents to dissolve both drug and PVP as matrix simultaneously15.


Supercritical fluid method:

Supercritical fluid methods are mostly applied with carbon dioxide (CO2), which is used as either a solvent for drug and matrix or as an anti-solvent 16. When supercritical CO2 is used as solvent, matrix and drug are dissolved and sprayed through a nozzle, into an expansion vessel with lower pressure and particles are immediately formed. The adiabatic expansion of the mixture results in rapid cooling. This technique does not require the use of organic solvents and since CO2 is considered environmentally friendly, this technique is referred to as ‘solvent free’. The technique is known as Rapid Expansion of Supercritical Solution (RESS)17. However, the application of this technique is very limited, because the solubility in CO2 of most pharmaceutical compounds is very low (<0.01%) and decreases with increasing polarity.


Schematic diagram of precipitation from supercritical solutions—rapid expansion of supercritical solution (RESS). Reproduced with permission from Kakumanu, VK and Bansal, AK.

Other methods:

Other methods include:

a)       Supercritical fluid impregnation

b)       Electrostatic spinning process

a) Supercritical fluid impregnation:

Supercritical fluid impregnation, the drug is dissolved in a supercritical fluid and exposed to solid matrix material that swells and absorbs the supercritical solution. By varying the pressure and the time of exposure, the diffusion process can be controlled. The absorption stops when the pressure is reduced. This process is investigated for polymethyl methacrylate.


b) Electrostatic spinning process:

The electrostatic spinning method technology used in the polymer industry combines solid solution/dispersion technology with nanotechnology. This technology is now applied in the pharmaceutical field. In this process, a liquid stream of a drug/polymer solution is subjected to a potential between 5 and 30 kV. When electrical forces overcome the surface tension of the drug/polymer solution at the air interface, fibers of submicron diameters are formed. As the solvent evaporates, the formed fibers can be collected on a screen to give a nonwoven fabric, or they can be collected on a spinning mandril. The fiber diameters depend on surface tension, dielectric constant, feeding rate, and electric field strength. Water-soluble polymers would be useful in the formulation of immediate release dosage forms, and water-insoluble (both biodegradable and nonbiodegradable) polymers are useful in controllable dissolution properties.



1. Detection of crystallinity in solid dispersions:

The following techniques are available to detect the degree of crystallinity:

a) Powder X-ray diffraction can be used to qualitatively detect material with long range order. Sharper diffraction peaks indicate more crystalline material. Recently developed X-ray equipment is semi-quantitative.

b) Infrared spectroscopy (IR) can be used to detect the variation in the energy-distribution of interactions between drug and matrix. Sharp vibrational bands indicate crystallinity. Fourier Transformed Infrared Spectroscopy (FTIR) was used to accurately detect crystallinities ranging from 1 to 99% in pure material 18.


2. Amount of crystalline material:

A frequently used technique to detect the amount of crystalline material is Differential Scanning Calorimetry (DSC). In DSC, samples are heated with a constant heating rate and the amount of energy necessary for that is detected. With DSC the temperatures at which thermal events occur can be detected. Thermal events can be a glass to rubber transition, recrystallization, melting or degradation. Furthermore, the melting- and recrystallization energy can be quantified. The melting energy can be used to detect the amount of crystalline material 19.


3. Detection of molecular structure in amorphous solid dispersions:

Confocal Raman Spectroscopy was used to measure the homogeneity of the solid mixture of ibuprofen in PVP.

4. Interaction between drug and carrier:

A thin layer chromatography is carried out to study the interaction between the drug and carriers to confirm the chemical stability of solid dispersion prepared.

Mobile phase: - Acetonitrile: Water: Acetic acid: Triethyl amine (47:53:0.1:0.03).

5. Drug Content Uniformity:

The prepared solid dispersions are tested for drug content uniformity. From each batch of solid dispersions taken, equivalent to 25mg of drug is dissolved in 100ml of methanol and measured the absorbance using UV-Visible spectrophotometer for analyzing drug content uniformity.

6. Drug Release Study:

The drug release study is carried out using USP XXIII dissolution apparatus with 900ml of pH 7.4 phosphate buffer as dissolution medium. Solid dispersion equivalent to 100mg of drug is taken in a hard gelatin capsule. The stirrer was adjusted to 75rpm. The temperature maintained at 37oC20. 5ml of aliquot samples of dissolution media is withdrawn at different time intervals and analyzed after suitable dilution by measuring absorbance using UV-Visible spectrophotometer. The volume withdrawn was replaced with fresh quantity of dissolution media. The percentage of drug dissolved at various time intervals was calculated and plotted against time.


Application of solid dispersions in dosage forms:

The formulation of solid dispersions into drug administration forms also presents a great challenge. Essential steps like milling, sieving or granulation can affect the properties of the solid dispersion. Stress induced crystallization has been observed for amorphous trehalose glasses resulting in degradation of the incorporated protein. Therefore, sugars with low crystallization tendency are preferred. Furthermore, many dissolution studies are performed with powders or grinded solid dispersions, instead of tablets. This is probably because disintegration of the tablet is problematic. Many matrices become waxy and sticky or even melt during tablet compaction. The two most used matrices, PEG and PVP, have very good binding properties. Moreover, they fill up the pores during the compaction process thereby hindering rapid dissolution of the tablet. Sometimes capping is caused by the elastic behavior of completely dry amorphous materials. The use of other excipients to prepare solid dispersion tablets with high tensile strength and proper dissolution and disintegration properties should be investigated. Finally, the application of fast release solid dispersions for non-oral routes needs to be investigated. The fast release of a highly lipophilic drug in the pulmonary mucosa could lead to rapid local action or rapid systemic absorption.



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Received on 23.06.2010          Modified on 02.07.2010

Accepted on 14.07.2010         © RJPT All right reserved

Research J. Pharm. and Tech. 4(3): March 2011; Page 331-334