Solid Dispersion a Promising Novel Approach for Improving the Solubility of Poorly Soluble Drugs
About Authors: Kushwaha Anjali*
Department of Pharmaceutics, Institute of pharmacy,
Bundelkhand university, Jhansi (U.P.), India
Reference ID: PHARMATUTOR-ART-1085
Solid dispersions is an efficient means of improving the dissolution rate and hence the bioavailability of a range of poorly soluble drugs. This article reviews the various types of solid dispersion, preparation techniques for solid dispersion and compiles some of the recent technologies. Some of the practical aspects to be considered for the preparation of solid dispersions, such as selection of carrier and methods of physicochemical characterization, along with nature of drugs in solid dispersions are also discussed. Finally, limited commercialization of solid dispersions and recent revival has been considered.
Therapeutic effectiveness of a drug depends upon the bioavailability and ultimately upon the solubility of drug molecules. Solubility behavior of a drug is one of the key determinants of its oral bioavailability. In recent years, the number of poorly soluble drug candidates has increased tremendously. The formulation of poorly soluble drugs for oral delivery presents a challenge to the formulation scientists. The rate and extent of dissolution of the active ingredient from any dosage form often determines the rate of extent of absorption of the drug. When an active agent given orally, it must first dissolve in gastric and/or intestinal fluids before it can then permeate the membranes of the GI tract to reach systemic circulation. Therefore, a drug with poor aqueous solubility will typically exhibit dissolution rate limited absorption, and a drug with poor membrane permeability will typically exhibit permeation rate limited absorption. Hence, two areas focus on improving the oral bioavailability of active agents include: (i) enhancing solubility and dissolution rate of poorly water-soluble drugs and (ii) enhancing permeability of poorly permeable drugs. This article focuses on the former, in particular, the use of solid dispersion technologies to improve the dissolution characteristics of poorly water-soluble drugs and in turn their oral bioavailability. In case of poorly water soluble drugs, dissolution may be the rate-limiting step in the process of drug absorption. Drug with poor water solubility have been shown to be unpredictably and slowly absorbed compared with drugs of higher solubility. Therefore, a better oral, parenteral, or topical formulation can be developed by increasing the water solubility of the drugs. There are various techniques available to improve the solubility of poorly soluble drugs, such Micronization, Nanosuspension, Modification of the crystal habits, Eutectic mixtures, Solid dispersions, Micro emulsions, Self micro emulsifying drug delivery systems, cyclodextrin inclusion and lipid based delivery systems etc. This review focuses on the solid dispersion technique of solubilization for the attainment of effective absorption and improved bioavailability. Solid dispersion is one of the most promising approaches for solubility enhancement. In the biopharmaceutical classification system (BCS) drugs with low aqueous solubility and high membrane permeability are categorized as Class II drugs Therefore, solid dispersion technologies are particularly promising for improving the oral absorption and bioavailability of BCS Class II 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 disappointing. 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 reduction. In case of solid dispersion drug disperse in the matrix generally a hydrophilic matrix and a hydrophobic drug, thereby forming a solid dispersion. 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. (J Anil Shinde, 2007; Ghaste Rahul et al., 2009)
“The term SD defined as the dispersion of one or more active ingredients (hydrophobic) in an inert carrier or matrix (hydrophilic) at solid state prepared by the melting (fusion), solvent, or melting-solvent method”. 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 particles. Therefore, based on their molecular arrangement, six different types of solid dispersions can be distinguished. Moreover, not the preparation method but the molecular arrangement governs the properties of solid dispersions.
TYPES OF SOLID DISPERSION
Based on their molecular arrangement, six different types of solid dispersions can be distinguished as shown in table are ………
1. Simple eutectic mixture
2. Amorphous precipitations in crystalline matrix
3. Solid solutions
i. According to their miscibility
a. Continuous solid solutions
b. Discontinuous solid solutions
ii. According to the way in which the solvate molecules are distributed in the solvendum
a. Substitutional solid solutions
b. Interstitial solid solutions
4. Glass suspension
5. Glass suspension
6. Glass solution
SIMPLE EUTECTIC MIXTURES
When a mixture of A and B with composition E is cooled, A and B crystallize out simultaneously, whereas when other compositions are cooled, one of the components starts to crystallize out before the other. 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. The large surface area of the resulting suspension should result in an enhanced dissolution rate and thereby improved bioavailability. (Sekiguchi K et al.,1961; Goldberg A et al.1966)
According to their miscibility two types of solid solution are-----
CONTINUOUS SOLID SOLUTIONS
In a continuous solid solution, the components are miscible in all proportions. Theoretically, this means that the bonding strength between the two components is stronger than the bonding strength between the molecules of each of the individual components. Solid solutions of this type have not been reported in the pharmaceutical literature to date.
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