Solubility Enhancement and physicochemical characterization of Inclusion Complexes Of Quinazoline

-4(3H)- ones and β-cyclodextrin

Zirmire Ravindra Kailasrao,M.Sc.-II, Sem IV,

Roll:99/03PGIII/120005

Presented By,

Contents

1) Introduction.

2) Review and Literature.

3) Materials and Methodology.

4) Results

5) Discussion

6) Conclusion

8) List of references

WHAT IS QUINAZOLINE?

A heterocyclic compound.

With benzene and pyrimidine rings.

Having antimicrobial, antiviral, anticancer sedative, analgesic, anticonvulsant, antitussive, myorelexant,, hypotensive, antiallergic, bronchodilating activities.

Having low water solubility.

WHAT IS CYCLODEXTRIN?

A bacterial digest that he had isolated from starch.

Cyclic oligosachharide of glucose enzyme Cyclodextrine Glucanotransferase..

Outer polar and non polar inside cavity

Types of Cyclodextrines:

1) α-Cyclodextrin

2) β-cyclodextrin

3)ϒ-Cyclodextrin

PROPERTIES OF CYCLODEXTRINS

3.1)SCHEME OF SYNTHESIS OF COMPOUNDS

3)Material and Methods

3.2)PREPARATIPON OF COMPLEX

3.2.1)In Silico complex formation:

By ChemDraw 8.0 software.

3.2.2) Physical mixture (PM) :

Compound and β-CD [1:1 molar ratio] taken together.

Crushed together for 40 min.

3.2.3) Kneading method (KN):

PM of 1:1 molar ratio of compounds and β-CD crushed in

mortar with a small volume of water-ethanol solution.

The thick slurry was kneaded for 40 min and then dried at 40

0C.

3.2.4)COEVAPORATION METHOD (COE):

Aq.solution of β-CD was added to an alcoholic solution of compound.

The resulting mixture stirred for 1 hr,the solution was sieved through a Whatman filter paper.

Filtrate Evaporated at a temp of 450C until dry

3.2.5) FREEZE–DRYING METHOD (FD)

Physical mixtures of compounds and β-CD at a molar ratio of 1:1 were taken

Added to 500 ml double distilled water.

Stirred for 3 days

The filtrate was freeze-dried.

3.3)CHARACTERIZATION OF QUINAZOLINE-4(3H) - ONES AND BETA-CD (1:1) COMPLEX

3.3.1)UV spectroscopic study:

UV-1700 Spectrometer (Jasco, Tokyo, Japan) was used with 1 cm matched quartz cuvettes. All measurements were recorded in the wavelength range 200–500 nm

3.3.1.1)UV ABSORBANCE STUDY BY CHANGING THE CONCENTRATION OF COMPOUND ONLY:

The concentration of compounds was increased from 1,3,5,7,9mg/ml by keeping the

concentration of β cyclodextrin constant.

The UV spectra was taken

3.3.1.2)EFFECT OF CRUSHING TIME ON COMPLEX FORMATION:

Only the crushing time for the complex formation was varied by keeping all parameters constant as 0min., 20 min., 40 min. and the UV spectra was observed.

3.3.1.2.3)Determination efficiency of complex formation by different methods.

The complexes of the compounds were prepaired by the three different methods.

The Complex formed were dissolved in water and Uv absorbance was taken at 280 nm.

3.3.2)FOURIER TRANSFORM INFRARED SPECTROPHOTOMETRY [FT-IR]:

The FT-IR spectra of compounds`1A,2A, complexes of different compounds and cyclodextrin were taken in Nujol and compared for the presence of different peaks in the FT-IR spectra(Shimadzu FT-IR 8300).

3) THIN LAYER CHROMATOGRAPHY:

3.3.3.1) TLC of 1A-β CD complex:

The compound was dissolved in ethanol and complexe was dissolved to distilled water.

TLC was done using the solvent system Methanol: Acetone: water (6:2:2).

3.3.3.2) TLC OF 2A- ΒETA CD COMPLEX:

The compound was dissolved in ethanol and complex was dissolved to distilled water.

TLC was done using the solvent system Pet ether: Ethyl acetate:Acetone (3:1:2).

4)RESULTS

4.1) In vitro complex formation:

Fig.. the structure of complex of 1A compound–Beta cyclodextrin

4.2) UV SPECTROSCOPIC CHARACTERIZATION OF COMPLEX:

4.2.1) UV spectra of different concentration of 1A in constant concentration of Beta-CD:

Fig.6 UV spectra of different drug concentrations in water.

4.2.2) EFFECT OF CRUSHING TIME ON COMPLEX FORMATION:

Fig.7 Effect of crushing time on 1A-Beta-cyclodextrin complex formation.

4.2.3) EFFICIENCY OF DIFFERENT METHODS ON COMPLEX FORMATION:

Fig.8.Efficiency of different methods for 1A-Beta cyclodextrin complex formation.

 4.3) FT-IR SPECTROSCOPY:

4.3.1) FT-IR of 1A- β cyclodextrin complex:

Fig.9. a)Drgu1A, b)Beta cyclodextrin ,c)PM of 1A-Beta cyclodextrin ,d)KN of 1A-Beta cyclodextrin.

4.3.2) FT-IR OF 2A- BETA CYCLODEXTRIN COMPLEX:

Fig.10. a) compound 2A, b)Beta cyclodextrin ,c)PM of 2A-Beta cyclodextrin ,d)KN of 2A-Beta

cyclodextrin

4.4) THIN LAYER CHROMATOGRAPHY:

4.4.1) TLC OF 1A :

Fig11. TLC of 1A, PM, KN, CD

4.4.2) TLC of 2A:

5)DISCUSSION:

In silico study confirmed the complex as the complex formation have significant binding energy.

The crushing time of 40 minutes was found to be efficient.

Small shift in absorption maxima after complex formation.

Kneaded method was seen to be most efficient method for the complex formation.

For 1A, changes within 680–765cm-1, the stretching frequency range for the Phenyl group of the compound 1A it may be due to the inclusion of the benzene ring inside the cyclodextrin which lead to the considerable decrease in the absorbance of IR.

The changes are seen for the peak 1692 cm-1 which is specific peak for the functional group γ-C=N may be as it formed the H-bond with to the inside Hydrogen atoms.

Changes in the range of 1200-1258 cm-1 of γ-C=O this may be due to the formation of the hydrogen bond by oxygen atom with the internally located H atoms of Beta CD.

For 2A, changes in absorption spectra within 684–858cm-1 it corresponds to the Phenyl groups of the compound 2A it gives the possibility of inclusion of the Phenyl group inside the host.

Many other small peaks got masked .

TLC study confirms that the polarity of the drug got increased as the compound got entered inside the Cyclodextrin so that in remain to the back side of the compounds as compared to Compounds.

Due to more polar nature of the Beta CD it interact more with the Silica gel than the mobile phase.

The complex formed was confirmed by UV.,FT-IR,TLC.

6)CONCLUSION

The solubility of compound 1A and 2A was successfully enhanced in water by formation of inclusion complex with beta cyclodextrin.

The different method of preparing complexes has different impact in enhancing the solubility.

Kneaded method is most efficient method.

It will be a most economical method for the solubilisation and to enhance bioavailability and pharmaceutical potential.

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