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Drug dispersion in carriers4,16-19
A.    Solid solution:
A solid solution is a binary system comprising of a solid solute molecularly dispersed in a solid solvent. Since the two compartments crystallize together in a homogeneous one phase system, solid solutions are also called as molecular dispersion or mixed crystals. Because of reduction in particle size to molecular level, solid solutions show greater aqueous solubility and faster dissolution than eutectics and solid dispersion. They are generally prepared by fusion method whereby physical mixture of solute and solvent are melted together followed by rapid solidification. Such systems, prepared by fusion are called as melts e.g. griseofulvin- succinic acid. The griseofulvin from such solid solution dissolves 6 to 7 times faster than pure griseofulvin. Mechanism of solid solution for solubility enhancement is when the binary mixture exposed to water, the soluble carrier dissolves rapidly leaving the insoluble drug in a state of microcrystalline dispersion of very fine particles, and when the solid solution, which is said to be in a state of randomly arranged solute and solvent molecules in the crystal lattice, is exposed to the dissolution fluid, the soluble carrier dissolves rapidly leaving the insoluble drug stranded at almost molecular level.

B.     Eutectic mixtures:
When the eutectic mixture is exposed to water, the soluble carrier dissolves leaving the drug in microcrystalline state which solubilizes rapidly. Eutectic mixture differs from solid solution in that the fused melt of solute-solvent show complete miscibility but negligible solid-solid solubility i.e. such system are basically intimately blended physical mixture of two crystalline components. A simple eutectic mixture consists of two compounds which are completely miscible in the liquid state but only to a very limited extent in the solid state. 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. The large surface area of the resulting suspension should result in an enhanced dissolution rate and thereby improved bioavailability.

C.    Solid dispersion:
Solid dispersion (SD) technique has been widely used to improve the dissolution rate, solubility and oral absorption of poorly water-soluble drugs. Solid dispersion is defined as the dispersion of one or more active ingredients in an inert excipient or matrix (carrier), where the active ingredients could exist in finely crystalline, solubilised or amorphous state. Once the solid dispersion is exposed to aqueous media and the carrier dissolve, the drug is released as very fine to colloidal particles. Because of greatly enhanced surface area obtained in this way, the dissolution rate and the bioavailability of poorly water-soluble drugs are expected to be high. The enhanced solubility and dissolution rate of drugs from solid dispersions is based on following mechanisms:
a.       Reduction in particle size provides large surface area.
b.      Particles with improved wettability and dispersibility of drug.
c.       Particles with higher porosity.
d.      Drugs in amorphous state.
e.       Solubilizing effect on the drug by water soluble carrier.
f.       Formation of metastable dispersion.

Various pharmaceutical approaches for the preparation of solid dispersion include co-precipitation, lyophilization, spray drying, melting solvent method, melt extrusion method, solvent evaporation, fusion and powder mixing methods.

Carriers, which are soluble and dissolve in water at a fast rate, are widely used in pharmaceutical formulations to enhance solubility and dissolution of drugs. Various carriers are used for solubilty enhancement listed mentioned in the table 2.

Table 2: List of carriers used for solubility enhancement

Sr. no.


Examples of carrier



Deoxycholic acid, tweens, spans, polyoxyethylene stearate, renex, poloxamer 188.



Urea, sodium acetate, nicotinamide, sodium benzoate, sodium salicylate, sodium-o-hydroxy benzoate.


Insoluble or enteric polymer

Eudragit L100, Eudragit S100, Eudragit RL,

Eudragit RS, Hydroxy propyl methyl cellulose phthalate.



Citric acid, succinic acid.



Dextrose, sucrose, galactose, sorbitol, maltose, mannitol, lactose.


Polymeric materials

Povidone (PVP), polyethylene glycol (PEG), cyclodextrin,

hydroxypropyl methyl cellulose, methyl cellulose, hydroxy ethyl cellulose, hydroxy propyl cellulose.



Microcrystalline cellulose, dicalcium phosphate, silica gel, sodium chloride.

The solubility of the drug is the factor that controls the formulation of the drug as well as therapeutic efficacy of the drug, hence the most critical factor in the formulation development. There are various available techniques, alone or in combination can be used to enhance the solubility of the drug. A drug administered in solution form immediately available for absorption and efficiently absorbed than the same amount of drug administered in a solid dosage form such as tablet or capsule. Solubility is a most important parameter for the oral bioavailability of poorly soluble drugs. Dissolution of drug is the rate determining step for oral absorption of the poorly water soluble drugs, which can subsequently affect the in vivo absorption of drug. Currently only 8-10% of new drug candidates have both high solubility and permeability. Because of solubility 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 poorly soluble drugs with the help of various techniques as mentioned above. Numerous technological advancements have been introduced for solubility and dissolution enhancement of poorly water soluble drugs.

1.    Kushwaha A. Solid dispersion – a promising novel approach for improving the solubility of poorly soluble drugs. IJPSR 2011; 2(8): 2021-2030.   
2.    Satish KP, Kalpesh SW, Venkatesh BP, Anup MA, Dheeraj TB. Strategies for solubility enhancement of poorly soluble drugs. International Journal of Pharmaceutical Sciences Review and Research 2011; 8(2): 74-80.  
3.    Indian Pharmacopoeia, Ministry of Health and family welfare, Government of India, Published by the controcller of publications, Delhi; 1996.
4.    Ahmad Z, Maurya N, Mishra KS, Khan I. Solubility enhancement of poorly water soluble drugs: a review. International Journal of Pharmacy & Technology 2011; 3(1): 807-823.
5.    USP-NF. The Official Compendia of Standards. Reference Table/Description And Solubility, USP 29; 2006: 3191  
6.    Amidon GL, Lennernas H, Shah VP, Crison JR. A Theoretical basis for a Biopharmaceutic Drug Classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12: 413-420.
7.    Kawashima Y, Saito M, Takenaka H. Improvement of solubility and dissolution rate of poorly water-soluble salicylic acid by a spray-drying technique. J Pharm Pharmacol 1975; 27(1): 1-5.
8.    Sekiguchi K, Obi N. Studies on absorption of eutectic mixtures. I. A comparison of the behavior of eutectic mixtures of sulphathiazole and that of ordinary sulphathiazole in man. Chem Pharm Bull 1961; 9: 866-872.
9.    Emara LH, Badr RM, Elbary AA. Improving the dissolution and bioavailability of nifedipine using solid dispersions and solubilizers. Drug Dev Ind Pharm 2002; 28: 795-807.   
10.    Phillips EM, Stella VJ. Rapid expansion from supercritical solutions: application to pharmaceutical processes. Int J Pharm1993; 94: 1-10.
11.    Subramaniam B, Rajewski RA, Snavely K. Pharmaceutical processing with supercritical carbon dioxide. J Pharm Sci 1997; 86: 885-890.
12.    Sunkara G, Kompella UB. Drug delivery applications of supercritical fluid technology. Drug Del Technol 2002; 2: 44-50.
13.    Ran Y, Zhao L, Xu Q, Yalkowsky H. Solubilization of cyclosporin A. AAPS Pharm Sci Tech. 2001; 2(1): 1-4.    
14.    Bhise S, Chaulang G, Patel P, Bhosale A, Hardikar S. Superdisintegrants as solubilizing agents. Research J Pharm And Tech 2009: 2(2): 387-391.         
15.    Truelove J, Bawarshi?Massac R, Chen NR, Hussain A. A solubility enhancement of some developmental anti?cancer analog by complexation with nicotamide. Int J Pharm 1987; 19: 17?25.    
16.    Khoo SM, Porter CJH, Charman WN. The formulation of halofantrine as either nonsolubilising PEG 6000 or solubilising lipid based solid dispersions: physical stability and absolute bioavailability assessment. Int J Pharm 2000; 205: 65-78.
17.    Hirasawa N, Ishise S, Miyata H, Danjo K. Application of nilvadipine solid dispersion to tablet formulation and manufacturing  using crospovidone and  methylcellulose as dispersion carriers. Chem Pharm Bull 2004; 52: 244-247.
18.    Craig DQM. The mechanisms of drug release from solid dispersion in water solublepolymers. Int J Pharm 2002; 203: 131-144.
19.    Chiou W L, Riegelman S. Pharmaceutical applications of solid dispersion systems. J Pharm Sci1971; 60: 1281-1302.
20.    Chowdary KPR, Madhavi BLR. Novel drug delivery technologies for insoluble drugs. Ind Drugs 2005; 42(9): 557-563.


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