LIQUISOLID TECHNOLOGY: AN EMERGING AND ADVANCE TECHNIQUE FOR ENHANCING SOLUBILIZATION

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ABOUT AUTHORS:
Imran khan*, M. Idreesh khan, Unis khan
Dept. of Pharmaceutics in Shri Ram College of pharmacy, Banmore, Morena,
Madhya Pradesh, India
khan.imran731@gmail.com

ABSTRACT:
This is the novel approach for enhancing dissolution and bioavailability of BCS-II class drugs. Solubility is the major problem in the development of pharmaceutical dosage forms. Liquisolid technique is the novel and promising technique to overcome these problems. The liquisolid systems are to improve the dissolution properties of water insoluble agents. For enhancing the dissolution rates for water insoluble drugs we used carrier and coating materials like microcrystalline cellulose (Avicel), silica (Aerosil), sodium starch glycolate and magnesium stearate etc. These agents can significant effect on dissolution properties of water insoluble drugs.

REFERENCE ID: PHARMATUTOR-ART-2173

PharmaTutor (ISSN: 2347 - 7881)

Volume 2, Issue 6

Received On: 30/03/2014; Accepted On: 04/04/2014; Published On: 01/06/2014

How to cite this article: I Khan, MI Khan, U Khan; Liquisolid Technology: An Emerging and Advance Technique for Enhancing Solubilization; PharmaTutor; 2014; 2(6); 31-41

INTRODUCTION:
Solubility is one of the important parameter to achieve the desired concentration of drug in systemic circulation for pharmacological response to be shown.1 two consecutive transport processes can be identified to describe the oral absorption of drugs from solid dosage forms.
(1) Dissolution of the drug in vivo to produce a solution
(2) Transport of the dissolved drug across the G.I. membrane.2

Poorly water soluble drugs are defined as those with high permeability but whose solubility in aqueous media is not sufficient for the whole dose to be dissolved in the gastrointestinal tract. For these substances dissolution is therefore the rate determining step to absorption. The poor dissolution rates of poorly water soluble drugs is still a substantial problem confronting drug development, such as hindering the development of parenteral products and limiting the bioavailability of oral products.3

The term “water-insoluble drugs” are the drugs which are known as-

Table: Different solubilities

Sparingly water-soluble

1 part of solute to 100 parts of water

Slightly water-soluble

1 part of solute into 100 to 1000 parts of water

Very slightly water soluble

1 part of solute into 1000 to 10,000 parts of water

Solubilization: -Solubilization is the process of bringing into solution substances which are insoluble or sparingly soluble in water.

Solubilization techniques in brief: there are various techniques available to improve the solubility of poorly soluble drugs. Some of the approaches to improve the solubility are:4

PH adjustment:
It is well documented that the influence of the changes in pH within the gastrointestinal tract upon the bioavailability of pharmaceuticals. The absorption of drug is largely dependent upon diffusion, which varies with pH of the individual regions within the gastrointestinal tract, the pKa of the drug and permeability, which are not only moderated by the surface area of the region in which it is released, but also the regional pH effects upon drug ionization. By applying a pH change, poorly water soluble drugs with parts of the molecule that can be protonated (base) or deprotonated (acid) may potentially be dissolved in water. While the importance of critical parameters like salt selection and pH adjustment has been stressed on pre-formulation, the use of pH altering excipients within drug delivery systems is also of significant utility. pH adjustment can in principle be used for both oral and parenteral administration.

Micro-emulsion:
A micro emulsion is an optically clear pre-concentrate, isotropic, thermo dynamically stable transparent (or translucent) system, containing a mixture of oil, hydrophilic surfactant and hydrophilic solvent which dissolves a poorly water soluble drug. Upon contact with water, the formulations spontaneously disperse (or ‘self emulsifies’) to form a very clear emulsion of exceedingly small and uniform oil droplets containing the solubilized poorly soluble drug. Micro-emulsions have been employed to increase the solubility of many drugs that are practically insoluble in water, along with incorporation of proteins for oral, parenteral, as well as percutaneous/transdermal use.

Self-emulsifying drug delivery systems:
Self-emulsifying or self-micro emulsifying systems use the concept of in situ formation of emulsion in the gastrointestinal tract. The mixture of oil, surfactant, co-surfactant, one or more hydrophilic solvents and co-solvent forms a transparent isotropic solution that is known as the self-emulsifying drug delivery system (SEDDS)

Manipulation of solid state:
From the stability and bioavailability aspects, the crystalline form of a drug is of pharmaceutical importance. Polymorphism (existence of a drug substance in multiple crystalline forms) can cause variations in melting point, density, stability and drug solubility as these properties depend on the escaping tendency of the molecules from a particular crystalline structure. As a rule, for a drug that have the highest order of crystallinity is the most stable form, exists in multiple polymorphic forms, i.e. with the least amount of free energy, and, consequently, possesses the highest melting point and the least solubility. By controlling the crystallization process, amorphous or Meta stable forms of drugs possessing high free energy can be forcibly created. They offer the advantage of higher solubility but suffer from stability issues unless stabilizers intended to inhibit crystal growth are incorporated in the formulation.

Particle size reduction:
The bioavailability of poorly soluble drugs is often intrinsically related to drug particle size. By reducing particle size, the increased surface area may improve the dissolution properties of the drug to allow a wider range of formulation approaches and delivery technologies.

Co-solvency:
The solubility of a poorly water soluble drug can be increased frequently by the addition of a water miscible solvent in which the drug has good solubility known as co-solvents. The use of co solvents is a highly effective technique to enhance the solubility of poorly soluble drugs.

Micellar solubilization:
The use of surfactants to improve the dissolution performance of poorly soluble drug products has also been successfully employed. Surfactants can lower surface tension and improve the dissolution of lipophilic drugs in aqueous medium. Commonly used non-ionic surfactants include polysorbates, polyoxyethylated castor oil, polyoxyethylated glycerides, lauroyl macroglycerides and mono- and di-fatty acid esters of low molecular weight polyethylene glycols.

Micelles are divided into 2 categories-

Mixed micelles:
Mixed micelles have a hydrophobic core in which low soluble compounds can dissolve. The micelle solubilized host molecules (i.e. drugs) in the micelle volume, but the penetration into the micelle depends over all on the inner space of the micelle, on the hydro-phobicity of the drug and on the charge of the incorporated molecule. The interaction between micelles and lipophilic drugs leads to the formation of mixed micelles (MM), often called swollen micelles, too.

Polymeric Micelles:
Amphiphilic polymers assemble into nano-scopic supra molecular core-shell structures, known as polymeric micelles, which are under extensive study for drug delivery. Polymeric micelles may be safe for parenteral administration relative to existing solublizing agents, permitting an increase in the dose of potent toxic and poorly water soluble compounds. Polymeric micelles solubilized important poorly water-soluble compounds.

Hydrotropy:
Hydrotropy is a solubilization process whereby addition of a large amount of second solute results in an increase in the aqueous solubility of another solute. Hydrotropy designate the increase in solubility in water due to the presence of large amount of additives.

Solid Dispersions:
In this technique, a poorly soluble drug is dispersed in a highly soluble solid hydrophilic matrix, which enhances the dissolution of the drug. Solid dispersion techniques can yield eutectic (non-molecular level mixing) or solid solution (molecular level mixing) products. Presence of the drug in microcrystalline state, improved wettability and formation of high free energy amorphous forms of the drug during solid dispersion formation contribute towards enhancement of drug solubilization.The most commonly used hydrophilic carriers for solid dispersions include polyvinylpyrrolidone, polyethylene glycols, Plasdone-S630, Tween-80, Docusate sodium, Myrj-52, Pluronic-F68 and Sodium Lauryl Sulphate used.

Nano-suspension:
This technology is applied to poorly soluble drugs that are insoluble in both water and oils. The particle size distribution of the solid particles in Nano-suspensions is usually less than one micron with an average particle size ranging between 200 and 600 nm.


Fig: Different method for enhancing the solubility of drugs

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