Open  Access Full Text Article                                                                                                              Review Article

A Review on Solubility Enhancement by Solid Dispersion Method

Laxmikant B. Dhande*¹, Madhuri T. Deshmukh ², Abhijit N. Khopade ², Rajkumar V. Shete ³, Vaibhavi V. Kunjir²

¹ M. Pharm. Student, Department of pharmaceutics, Rajgad Dnyanpeeth’s College of Pharmacy, Bhor-   412206   Pune, Maharashtra, India

² Professor, Department of Pharmaceutics, Rajgad Dnyanpeeth’s College of Pharmacy, Bhor-   412206   Pune, Maharashtra, India

³ Principal, Department of Pharmacology, Rajgad Dnyanpeeth’s College of Pharmacy, Bhor-   412206   Pune, Maharashtra, India

INTRODUCTION:

The oral route is the most convenient and preferred method for administration of drug due to ease of administration and convenience. Because of a patient’s prospective, oral route is a comfortable and a familiar means of taking medication¹. Hence orally administrated medications are more effective when compared with other routes of administration. The minimum 40% of the novel drug from the pharmaceutical industries are showing poor capability of solubilization in water, because of slow release, slow dissolution and poor bioavailability which need to administration of large dose for producing desirable pharmacological effect^2,7,8. To overcome these problems best option is solving solubility problem, enhancing solubility, dissolution rate of poor drugs which are water soluble by solid dispersion method. Hence solid dispersion is one of the best techniques. for enhancing the dissolution rate, solubility, and oral bioavailability of poor water-soluble drug. The two areas of pharmaceutical research that focus on improving oral bioavailability of active agent which includes enhancing solubility and dissolution rate of poorly water-soluble drug and enhancing permeability of poorly permeable drug^3,9. This narrative review focuses on the use of solid dispersion technique and method to improve the dissolution characteristics of poorly water- soluble drug and their oral bioavailability.

Table 1: BCS Classification System ^3,10

Table 2: Materials used as carrier for solid dispersion ^1,3

TYPE OF SOLID DISPERSION:^3,11

• Eutectics
• Amorphous solid solutions
• Solid solution

1. Continuous solid solution
2. Discontinuous solid solution
3. Substitutional solid solution
4. Interstitial solid solution

• Glass solution and suspension
• Eutectics Mixtures:

A simple ieutectic imixture iconsists iof itwo icompounds which are completely imiscible in the iliquid istate but only to a very limited iextent in the solid state. It is prepared by rapid solidification of fused melt of two components that show complete liquid miscibility but negligible solid-solid solution ^3,11,12.

Figure 1: Eutectics mixtures

• Amorphous solid solution:

This is similar to simple eutectic mixtures but only difference is that drug is precipitated out in an amorphous form^3,13,14.

Figure 2: Amorphous solid solution

• Solid solution:

Solid isolutions are icomparable to iliquid isolutions, iconsisting of just one phase iirrespective of the inumber of icomponents. In the case of solid solutions, the drug's iparticle size has been ireduced to its iabsolute iminimum viz. the imolecular dimensions¹⁴ and the dissolution rate is determined by the dissolution rate of the carrier. Classified iaccording to itheir imiscibility (discontinuous solid solutions versus continous) or isecond, iaccording to the way in iwhich the isolvate imolecules are idistributed in the isolvendum (interstitial or amorphous, substitutional)³.

1. Continuous solid solution:

In a continuous isolid solution, the icomponents are miscible in all proportions. Theoretically, this means that the ibonding strength ibetween the two icomponents is istronger than the ibonding istrength between the imolecules of ieach of the individual icomponents. Solid isolutions of ithis itype ihave not ibeen ireported in the ipharmaceutical iworld itill idate^3,5.

1. Discontinuous solid solutions:

In the icase of idiscontinuous isolid isolutions, the isolubility of ieach of ithe icomponents in the iother component is ilimited. Due to ipractical iconsiderations it ihas ibeen isuggested by iGoldberg et al.that the term solid solution' ishould ionly ibe iapplied iwhen the imutual isolubility of the itwo icomponents iexceeds 5%^3,5.

Figure 3: Discontinuous solid solution

1. Subsitutional solid dispersions:

Substitution is ionly ipossible iwhen the isize of the isolute imolecules idiffers by less than 15% or so from that of the solvent molecules¹⁵. Classical isolid isolutions have icrystalline istructure, in iwhich the isolute imolecules can ieither isubstitute for solvent imolecules in the icrystal ilattice or fit into the intrsticies ibetween the solvent imolecule³.

Figure 4: Subsitutional solid solution

1. d) Interstitial solid solutions:

In interstitial isolid isolutions, the idissolved imolecules ioccupy the interstitial spaces ibetween the isolvent imolecules in the crystal lattice. Solute molecule diameter should be less than 0.59 times than that of solvent molecular diameter^3,5.

Figure 5: Interstitial solid solution

• Glass solution and suspensions:

Glass isolutions are ihomogeneous iglassy system in iwhich isolute idissolves in glass icarrier. Glass suspensions are imixture in iwhich iprecipitated iparticles are isuspended in iglass isolvent. Lattice ienergy is imuch ilower in iglass isolution and isuspension^3,5,14.

Solid Dispersion: Solid dispersion is defined as idispersion of one or imore iactive ingredient iinert icarrier or imatrix at isolid istate.

Figure 6: Solid dispersion of polymer matrix.

ADVANTAGES OF SOLID DISPERSION:

• Reduced particle size:

As the solid dispersions are having smallest particle size state and after carrier dissolution the drug is dispersed in dissolution medium. The principle of solid dispersion can be applied by creating a mixture of a poorly water-soluble drug and highly soluble carriers. Hence bioavailability can be improved by forming a high surface area resulting in an increased dissolution.

• Particles with Improved wettability:

The carrier increases the wettability properties of drug. Carriers mainly influence the drug dissolution profile by direct dissolution or by co-solvent effects.

• Particles with higher porosity:

In solid dispersion the particles ihas ibeen ifound to ihave a ihigher idegree of iporosity. It depends upon the carrier properties. As solid dispersion containing linear polymer which iproduces ilarger and imore iporous iparticles than those icontaining ireticular ipolymer iwhich result in a ihigher idissolution rate. The increase in the iporosity of isolid idispersion particles increases the drug release profile.

• Drugs in amorphous state:

The crystalline drug having poor water-soluble shows higher solubility when in the amorphous state. This can be achieved by using the drug in its amorphous state. Hence ihigher iamorphous icompositions can be iobtained by ichoosing icarriers, iwhich exhibit specific iinteractions iwith them³.

DISADVANTAGES OF SOLID DISPERSION:

1. The undefined condition of medication may experience crystalline state, in this way poor soundness is the issue of strong scattering.
2. Handling issue show up because of thickness of some strong scatterings.
3. In nearness of dampness and extraordinary temperature strong scattering might be disintegrated, that can result in precious stone development.
4. Shelf life forecast of indistinct material is troublesome.
5. Hygroscopicity of polymers utilized in strong scattering retains dampness that can result in change of nebulous structure into crystalline form.
6. The instability is the major disadvantage of the solid dispersion. The deteriorating effect on solid dispersions such as moisture and temperature have more on physical mixture because of tackiness it is difficult for east handling of solid dispersion.

APPLICATION:

• It is mainly applicable in obtaining homogeneous distribution of a small amount of drug in solid state.
• It helps to stabilize the unstable drug¹⁶.
• It is used to dispense both the liquid or gaseous compound in a solid dosage state.
• The fast release primary dose can be formulated in a sustained dosage form.
• It is also used to formulate sustained release of soluble drug by using poorly soluble or insoluble carrier.
• By polymorph is given in solid dispersion system such as solid solution, eutectic mixture^3,17.

METHOD OF PREPARATION:⁴

• Melting method
• Solvent evaporation method
• Lyophilization technique
• Melting solvent method
• Melt extrusion method
• Melt agglomeration process
• Spray drying
• Effervescent method
• Electrospinning
• Super critical fluid (SCF) Technology.

1) Melting method:

The melting and fusion method which involves the ipreparation of iphysical imixture of a idrug and a iwater-soluble icarrier and iheated it idirectly iuntil it melted. The mixture is melted first then isolidified irapidly in an ice-bath under ivigorous istirring. Then final solid mass is crushed, pulverized and sieving⁴.

• Solvent evaporation method:

In this method the mixture such as drug and carrier is dissolved in a common solvent which is then evaporated until free film is lefts, Further dried and sieved^2,18.

• Lyophilization technique:

In this method itransfer of iheat and imass take iplace from the iproduct iunder preparation. This itechnique was iproposed as an ialternative itechnique for the isolvent ievaporation. This is the type of a molecular mixing technique where the carrier and drug are co-dissolved by using common solvent. After this frozen and sublimed to obtain a lyophilization molecular dispersion^2,4.

• Melting solvent method:

In this method addition of ifixed iamount of solvent and then that isolution is introduceded into melted from of polyethylene glycol below 70⁰C. This method also used for thermolabile drug with high melting point. But limited drug is required with low therapeutic dose (below 50mg)^2,4.

• Melt extrusion method:

This method meanly preferred for thermolabile drug. The drug and carrier are mixed together and typically processed with a twin -screw extrusion. The mixture is then isimultaneously imelted, ihomogenized and then iextruded and ishaped as tablets, granules, pellets, sheets, sticks or powder. The intermediates are then ifurther iprocessed into iconventional itablets.^3,4.

• Melt agglomeration process:

In this method, the solid dispersion is prepared where the binder rols as a carrier. In iaddition to this, isolid idispersion are prepared ieither by iheating ibinder, drug and iexcipient to a itemperature iabove the imelting ipoint of the ibinder ( melt in procedure ) or by ispraying a idispersion of idrug in imolten ibinder on the iheated iexcipient (spray-on procedure) by iusing a high ishear imixer. A rotary processor is the ialternative iequipment for melt iagglomeration. The rotary processer is mainly preferable for high melt agglomeration. Because it is ieasier to icontrol the itemperature and ibecause a ihigher iibinder icontent can be incorporated in the iagglomerates^3,4.

• Spray drying:

In this method accurately weight amount of drug and lipid carrier are dissolved in methanol to obtain clear solution. This solution is there sprayed on lab scale with the help of dryer, which result in the formation of solid dispersion.²

• Effervescent method:

This is the method in which sodium bicarbonate and organic acid such as citric acid or succinic react with the each other to yield effervescence. But when combining of both that increased the dissolution and absorption rate of poor soluble drug^2,18.

• Electrospinning:

In this process solid fibers are produced from a polymeric fluid stream solution or melt delivered through a millimeter scale nozzle. It mainly involves the application of a istrong ielectrostatic ifield iover a iconductive icapillary iattach to a ireservoir icontaining a ipolymer isolution or melt and a iconductive icollection screen. With increase in the ielectrostatic ifield istrength up to but not iexceeding a icritical ivalue, icharge ispecies which iaccumulated on the isurface of a pendant drop, which destabilize the hemispherical shape in to a conical shape. Technique has much more potential for the production of inanofibers and icontrolling the irelease of ibiomedicine, It is simplest the cheapest technique utilized for the preparation of solid dispersion in further^3,4,5.

• Super critical fluid (SCF) Technology:

This is the super critical fluid anti-solvent technique, which involves the use of carbon dioxide as an anti-solvent for the solute.

After this solubilization of drug particles within supercritical fluid they may be recrystallized at great it reduced particle size. The flexibility and precision offered by supercritical fluid process allow micronization of drug particle, within narrow range of particle size obtained to sub-micro level. The current super critical fluid processes have the ability to demonstrate and to create nano-particular suspension of particle 5-2000 in the diameter. The spraying of the solution was done which is composed of the solute & the organic solvent into a continuous super critical phase following concurrently.⁴

CHARACTERIZATION OF SOLID DISPERSION:

Various methods for characterization of solid dispersion are mention below.

• Drug icarrier imiscibility

            Hot stage microscopy

• Powder x-ray diffractioon
• NMR 1H spin lattice relaxation time
• Differential scanning calorimetry
• Drug carrier interactions
• Raman spectroscopy
• Solid state NMR
• FT-IR spectroscopy
• Physical structure
• Dynamic vapor sorption
• Inverse gas chromatography
• Scanning electron microscopy
• Surface area analysis
• Surface properties
• Amorphous content
• Humidity stage microscopy
• DSC(MTDSC)
• ITC
• Hot stage microscopy
• Polarised light optical microscopy
• Powder X-Ray diffraction
• Stability
• Humidity studies
• Isothermal Calorimetry
• DSC (Tg, Temperature recrystallization)
• Dynamic vapor sorption
• Saturated solubility studies
• Dissolution enhancement
• Intrinsic dissolution
• Dynamic solubility
• Dissolution
• Dissolution in bio-relevant media.^2,3,4

CONCLUSION:

The method of solid dispersion is one of the effective approaches to enhance the solubility of poorly water soluble drug and to increase their bioavailability. Hence it is required to overcome some problems related to flow properties and stability of drug. Therefore the solid dispersion having synthetic or natural carrier which is low toxic, biocompatible and more easily available is an alternative and best choice for improving solubility of poorly water soluble BCS-II drug. The development of the release rate and oral bioavailability of poorly water-soluble drugs by using solid dispersion by careful choice of the carrier. It is also feasible to delay or slow down the release pattern of drug.

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