The document discusses the solubility enhancement and physicochemical characterization of inclusion complexes formed between quinazoline-4(3H)-ones and β-cyclodextrin. It outlines various methodologies for complex preparation, such as physical mixing and kneading, and characterizes the complexes using spectroscopic techniques. The study concludes that the kneading method is the most efficient for enhancing the solubility of the compounds in water.

1. 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,

2. Contents
1) Introduction.
2) Review and Literature.
3) Materials and Methodology.
4) Results
5) Discussion
6) Conclusion
8) List of references

3. 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.

4. 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

5. PROPERTIES OF CYCLODEXTRINS

6. 3.1)SCHEME OF SYNTHESIS OF COMPOUNDS
3)Material and Methods

7. 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.

8. 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 0
C.

9. 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

10. 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.

11. 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

12. 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

13. 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.

14. 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).

15. 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).

16. 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).

17. 4)RESULTS
4.1) In vitro complex formation:
Fig.. the structure of complex of 1A compound–Beta cyclodextrin

18. 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.

19. 4.2.2) EFFECT OF CRUSHING TIME ON COMPLEX
FORMATION:
Fig.7 Effect of crushing time on 1A-Beta-cyclodextrin complex formation.

20. 4.2.3) EFFICIENCY OF DIFFERENT METHODS ON
COMPLEX FORMATION:
Fig.8.Efficiency of different methods for 1A-Beta cyclodextrin complex formation.

21.
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.

22. 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

23. 4.4) THIN LAYER CHROMATOGRAPHY:
4.4.1) TLC OF 1A :
Fig11. TLC of 1A, PM, KN, CD
4.4.2) TLC of 2A:

24. 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.

25. 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.

26. 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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