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International Journal of Trend in Scientific Research and Development (IJTSRD)
Volume 6 Issue 4, May-June 2022 Available Online: www.ijtsrd.com e-ISSN: 2456 – 6470
@ IJTSRD | Unique Paper ID – IJTSRD50151 | Volume – 6 | Issue – 4 | May-June 2022 Page 851
Effect on Binary & Ternary Inclusion of Ibuprofen &
Different Amino Acid Complex on Phase Solubility
Ms. Chetana D. Patil1
*, Mr. Vaibhav C. Babar2
, Ms. Prajakta S. Kakade3
1
Principal, Jaywant Institute of Pharmacy Wathar Karad, Maharashtra, India
2
Department of Chemistry GIPER, Limb, Satara, Maharashtra, India
3
Lecturer, KFs Jaywant Institute of Pharmacy Wathar Karad, Maharashtra, India
ABSTRACT
The aim of present research was to formulate and characterize
inclusion complexes between β-cyclodextrin (β-CD) and Ibuprofen.
Equimolar/ β-CD solid system in the presence and absence of 0.2%
(w/v) β-CD was prepared. A phase solubility study was done to
estimate solubility constant (KS) and complexation efficiency (CE).
Improvement of KS and CE showed the additive effect of auxiliary
substances (β-CD). The dissolution properties of binary and ternary
systems were determined and compared with alone. The ternary
system has shown several times faster than the binary system of
Ibuprofen. The optimized binary and ternary systems were
characterized by phase solubility. These results showed that ternary
inclusion complexes were formed.
KEYWORDS: Ibuprofen, β-cyclodextrin leucine, glycine, Stability
constant
How to cite this paper: Ms. Chetana D.
Patil | Mr. Vaibhav C. Babar | Ms.
Prajakta S. Kakade "Effect on Binary &
Ternary Inclusion of Ibuprofen &
Different Amino Acid Complex on
Phase Solubility"
Published in
International Journal
of Trend in
Scientific Research
and Development
(ijtsrd), ISSN: 2456-
6470, Volume-6 |
Issue-4, June 2022, pp.851-854, URL:
www.ijtsrd.com/papers/ijtsrd50151.pdf
Copyright © 2022 by author(s) and
International Journal of Trend in
Scientific Research and Development
Journal. This is an
Open Access article
distributed under the
terms of the Creative Commons
Attribution License (CC BY 4.0)
(http://creativecommons.org/licenses/by/4.0)
INTRODUCTION
Ibuprofen is a poorly water-soluble drug. The aim of
this study was to determine whether inclusion
complexes betweenβ-cyclodextrin (βCD) and
Ibuprofen are formed and also studied effect of
auxiliary substance on Ibuprofen. The aim of present
research was to formulate and characterize inclusion
complexes between β-cyclodextrin (β-CD) and
Ibuprofen. Equimolar Ibuprofen/ β-CD solid system
in the presence and absence of 0.2% (w/v). A phase
solubility study was done to estimate solubility
constant (KS) and complexation efficiency (CE).
Improvement of KS and CE showed the additive
effect of auxiliary substances (β-CD). The dissolution
properties of binary and ternary systems were
determined and compared with Ibuprofen alone. The
ternary system has shown several times faster than the
binary system of Ibuprofen. The optimized binary and
ternary systems were characterized by phase
solubility. These results showed that ternary inclusion
complexes were formed.
The present study is intended to evaluate the
possibilities to improve ibuprofen an oral NSAID
drug - solubility in water, based on inclusion
complexes formation with β-cyclodextrin (β-CD),),
respectively, and also to estimate their composition
and apparent stability constants, Kst, from the phase-
solubility diagrams. We have noticed that the phase
solubility diagram for the repaglinide – HP-β-CD
inclusion complex is A type. Ability of the Ibuprofen
to form inclusion complexes with a variety of organic
compounds is based on their ability to provide a
hydrophobic cavity in aqueous solution for a
hydrophobic guest molecule. Ibuprofen served as a
versatile carrier for poorly water soluble drugs
increasing its solubility and dissolution rate through
the formation of inclusion complex. They are capable
of alleviating the undesirable properties of drug
molecule through the formation of inclusion complex.
Hydroxylpropyl-betacyclodextrin is mainly selected
for its higher solubility and this generally results in
IJTSRD50151
International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
@ IJTSRD | Unique Paper ID – IJTSRD50151 | Volume – 6 | Issue – 4 | May-June 2022 Page 852
more extensive solubilization ability towards
lipophilic molecule, with good safety.
DRUG PROFILE-
Ibuprofen is a medication in the nonsteroidal anti-
inflammatory drug (NSAID) class that is used for
treating pain, fever, and inflammation. This includes
painful menstrual periods, migraines, and rheumatoid
arthritis. About 60% of people improve with any
given NSAID, and it is recommended that if one does
not work then another should be tried. It may also be
used to close a patient ductus arteriosus in a
premature baby. It can be used by mouth or
intravenously. It typically begins working within an
hour. it works by inhibiting the production of
prostaglandins by decreasing the activity of the
enzyme cyclooxygenase. Ibuprofen might be a
weaker anti-inflammatory than other NSAIDs.
Structure:
Ibuprofen
Leucine
Glycine
Betacyclodextrin
MATERIALS AND METHODS
CHEMICAL-
0.1n NaOH, Ibuprofen, Beta-Cyclodextren, Glycine,
Leucin
Sr. No Name of equipment
1 Electron weighing balance
2 U.V. visible spectrometer
3 Electronic shaking machine
METHODS
Phase solubility
Phase solubility studies were performed according to
the method reported by Higuchi Connors. An excess
amount of Ibuprofen was added to 10 ml distilled
water containing various concentrations of β-CD (0-
0.1 M) within stopper tubes and mixture were shaken
for 24Hrs 37 at 150 rpm. After achieving
equilibrium the solution was filtered through 0.45µm
membrane filter paper. The sample was diluted
suitably and assayed for content Ibuprofen by U.V.
Spectrophotometer at 232 nm .The solubility constant
and complexation efficiency was calculated by using
the following equations.
Ks=
Ks=Stability constant
So=solubility of Ibuproefnin absence of CD
CE=
CE=Complexation Efficiency
Aqueous solubility
An excess amount of prepared binary and ternary
complex added into 10ml water in stopper tubes.
They were kept and shaking to achieve equilibrium
appropriate aliquots was withdrawn filtered through
What man filter paper no.41.The filtrate
analysedspectro photo metrically 232nm.
RESULT AND DISCUSSION:
Calibration curve of Ibuprofen-
Conc Abs
0.2 0.167
0.4 0.402
0.6 0.562
0.8 0.692
1 0.927
Table no.1 Absorbance
International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
@ IJTSRD | Unique Paper ID – IJTSRD50151 | Volume – 6 | Issue – 4 | May-June 2022 Page 853
Fig-1.Calibration graph of ibuprofen
BINARY INCLUSION GRAPHS-
Conc. Abs.
0.002 128
0.004 0.284
0.006 0.388
0.008 0.528
0.01 0.686
Table no 2. Absorbance
Fig no- 2.Binary inclusion graph
TERNARY INCLUSION GRAPH FOR
LEUCINE-
Conc Abs
2 0.484
4 0.499
6 0.509
8 0.513
10 0.52
Table no 3.Absorbance
Fig no -3.Ternary inclusion graph for leucine
TERNARY INCLUSION GRAPH FOR
GLYCINE-
Conc Abs
2 0.528
4 0.533
6 0.535
8 0.537
10 0.539
Table no- 4.Abs. of ternary inclusion of glycin
Fig no- 4. Ternary inclusion graph for glycine
Effect of polymer, Leucine on slope of phase solubility diagrams and stability constant (Ks) for binary and
tertiary system of Ibuprofen with β-CD-
Systems Slope Ks( ) Mean±SD Kts/Kbs C.E.
Ibuprofen-β-CD
68
0.995 95.765 95.765 1.01
Ibuprofen-β-CD-Leucine 0.002 0.945 98.764 2.999 0.002
Ibuprofen-β-CD Glycine 0.004 0.949 99.865 1.101 0.004
Table no- 5. Binary and ternary complex phase solublity
Kts/Kbs ratio of Ks for ternary and binary complexes; indicates mean of three readings; S.D.: Standard
deviation. P value compared to Ibuprofen-β-CD i.e. significant C.E.: Complexation efficiency.
CONCLUSION:
This study has revealed that the improving the
dissolution performance of Ibuprofen by its
complexation with β-CD in presence of Leucine.
Leucine showed a more pronounced effect on the
enhancement of aqueous solubility and faster rate
International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
@ IJTSRD | Unique Paper ID – IJTSRD50151 | Volume – 6 | Issue – 4 | May-June 2022 Page 854
than binary complex. Phase solubility study of binary
and tertiary systems shows that stability constant of
ternary system is higher than that of binary system.
Thus, addition of Leucine in tertiary complexes of β-
CD beneficial in terms of improvement in CE, Rate of
complex formation and enhancement of poorly water-
soluble Ibuprofen. Ternary complex system was also
found to give faster drug release as compared to pure
Ibuprofen
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[1] Drugbank (Hydrochlorothiazide). Available
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[2] Pdf Materials and Instrument –Shodhganga
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M., Epure C., Szabadai Z., Study of influence
of citric acid on albendazole complexation with
random methylated β – cyclodextrin, Farmacia,
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captopril - β – cyclodextrin, Farmacia, LV, 1,
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http://www.drugbank.ca/drug/DB00999.
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Effect on Binary and Ternary Inclusion of Ibuprofen and Different Amino Acid Complex on Phase Solubility

  • 1. International Journal of Trend in Scientific Research and Development (IJTSRD) Volume 6 Issue 4, May-June 2022 Available Online: www.ijtsrd.com e-ISSN: 2456 – 6470 @ IJTSRD | Unique Paper ID – IJTSRD50151 | Volume – 6 | Issue – 4 | May-June 2022 Page 851 Effect on Binary & Ternary Inclusion of Ibuprofen & Different Amino Acid Complex on Phase Solubility Ms. Chetana D. Patil1 *, Mr. Vaibhav C. Babar2 , Ms. Prajakta S. Kakade3 1 Principal, Jaywant Institute of Pharmacy Wathar Karad, Maharashtra, India 2 Department of Chemistry GIPER, Limb, Satara, Maharashtra, India 3 Lecturer, KFs Jaywant Institute of Pharmacy Wathar Karad, Maharashtra, India ABSTRACT The aim of present research was to formulate and characterize inclusion complexes between β-cyclodextrin (β-CD) and Ibuprofen. Equimolar/ β-CD solid system in the presence and absence of 0.2% (w/v) β-CD was prepared. A phase solubility study was done to estimate solubility constant (KS) and complexation efficiency (CE). Improvement of KS and CE showed the additive effect of auxiliary substances (β-CD). The dissolution properties of binary and ternary systems were determined and compared with alone. The ternary system has shown several times faster than the binary system of Ibuprofen. The optimized binary and ternary systems were characterized by phase solubility. These results showed that ternary inclusion complexes were formed. KEYWORDS: Ibuprofen, β-cyclodextrin leucine, glycine, Stability constant How to cite this paper: Ms. Chetana D. Patil | Mr. Vaibhav C. Babar | Ms. Prajakta S. Kakade "Effect on Binary & Ternary Inclusion of Ibuprofen & Different Amino Acid Complex on Phase Solubility" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456- 6470, Volume-6 | Issue-4, June 2022, pp.851-854, URL: www.ijtsrd.com/papers/ijtsrd50151.pdf Copyright © 2022 by author(s) and International Journal of Trend in Scientific Research and Development Journal. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0) INTRODUCTION Ibuprofen is a poorly water-soluble drug. The aim of this study was to determine whether inclusion complexes betweenβ-cyclodextrin (βCD) and Ibuprofen are formed and also studied effect of auxiliary substance on Ibuprofen. The aim of present research was to formulate and characterize inclusion complexes between β-cyclodextrin (β-CD) and Ibuprofen. Equimolar Ibuprofen/ β-CD solid system in the presence and absence of 0.2% (w/v). A phase solubility study was done to estimate solubility constant (KS) and complexation efficiency (CE). Improvement of KS and CE showed the additive effect of auxiliary substances (β-CD). The dissolution properties of binary and ternary systems were determined and compared with Ibuprofen alone. The ternary system has shown several times faster than the binary system of Ibuprofen. The optimized binary and ternary systems were characterized by phase solubility. These results showed that ternary inclusion complexes were formed. The present study is intended to evaluate the possibilities to improve ibuprofen an oral NSAID drug - solubility in water, based on inclusion complexes formation with β-cyclodextrin (β-CD),), respectively, and also to estimate their composition and apparent stability constants, Kst, from the phase- solubility diagrams. We have noticed that the phase solubility diagram for the repaglinide – HP-β-CD inclusion complex is A type. Ability of the Ibuprofen to form inclusion complexes with a variety of organic compounds is based on their ability to provide a hydrophobic cavity in aqueous solution for a hydrophobic guest molecule. Ibuprofen served as a versatile carrier for poorly water soluble drugs increasing its solubility and dissolution rate through the formation of inclusion complex. They are capable of alleviating the undesirable properties of drug molecule through the formation of inclusion complex. Hydroxylpropyl-betacyclodextrin is mainly selected for its higher solubility and this generally results in IJTSRD50151
  • 2. International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470 @ IJTSRD | Unique Paper ID – IJTSRD50151 | Volume – 6 | Issue – 4 | May-June 2022 Page 852 more extensive solubilization ability towards lipophilic molecule, with good safety. DRUG PROFILE- Ibuprofen is a medication in the nonsteroidal anti- inflammatory drug (NSAID) class that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. About 60% of people improve with any given NSAID, and it is recommended that if one does not work then another should be tried. It may also be used to close a patient ductus arteriosus in a premature baby. It can be used by mouth or intravenously. It typically begins working within an hour. it works by inhibiting the production of prostaglandins by decreasing the activity of the enzyme cyclooxygenase. Ibuprofen might be a weaker anti-inflammatory than other NSAIDs. Structure: Ibuprofen Leucine Glycine Betacyclodextrin MATERIALS AND METHODS CHEMICAL- 0.1n NaOH, Ibuprofen, Beta-Cyclodextren, Glycine, Leucin Sr. No Name of equipment 1 Electron weighing balance 2 U.V. visible spectrometer 3 Electronic shaking machine METHODS Phase solubility Phase solubility studies were performed according to the method reported by Higuchi Connors. An excess amount of Ibuprofen was added to 10 ml distilled water containing various concentrations of β-CD (0- 0.1 M) within stopper tubes and mixture were shaken for 24Hrs 37 at 150 rpm. After achieving equilibrium the solution was filtered through 0.45µm membrane filter paper. The sample was diluted suitably and assayed for content Ibuprofen by U.V. Spectrophotometer at 232 nm .The solubility constant and complexation efficiency was calculated by using the following equations. Ks= Ks=Stability constant So=solubility of Ibuproefnin absence of CD CE= CE=Complexation Efficiency Aqueous solubility An excess amount of prepared binary and ternary complex added into 10ml water in stopper tubes. They were kept and shaking to achieve equilibrium appropriate aliquots was withdrawn filtered through What man filter paper no.41.The filtrate analysedspectro photo metrically 232nm. RESULT AND DISCUSSION: Calibration curve of Ibuprofen- Conc Abs 0.2 0.167 0.4 0.402 0.6 0.562 0.8 0.692 1 0.927 Table no.1 Absorbance
  • 3. International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470 @ IJTSRD | Unique Paper ID – IJTSRD50151 | Volume – 6 | Issue – 4 | May-June 2022 Page 853 Fig-1.Calibration graph of ibuprofen BINARY INCLUSION GRAPHS- Conc. Abs. 0.002 128 0.004 0.284 0.006 0.388 0.008 0.528 0.01 0.686 Table no 2. Absorbance Fig no- 2.Binary inclusion graph TERNARY INCLUSION GRAPH FOR LEUCINE- Conc Abs 2 0.484 4 0.499 6 0.509 8 0.513 10 0.52 Table no 3.Absorbance Fig no -3.Ternary inclusion graph for leucine TERNARY INCLUSION GRAPH FOR GLYCINE- Conc Abs 2 0.528 4 0.533 6 0.535 8 0.537 10 0.539 Table no- 4.Abs. of ternary inclusion of glycin Fig no- 4. Ternary inclusion graph for glycine Effect of polymer, Leucine on slope of phase solubility diagrams and stability constant (Ks) for binary and tertiary system of Ibuprofen with β-CD- Systems Slope Ks( ) Mean±SD Kts/Kbs C.E. Ibuprofen-β-CD 68 0.995 95.765 95.765 1.01 Ibuprofen-β-CD-Leucine 0.002 0.945 98.764 2.999 0.002 Ibuprofen-β-CD Glycine 0.004 0.949 99.865 1.101 0.004 Table no- 5. Binary and ternary complex phase solublity Kts/Kbs ratio of Ks for ternary and binary complexes; indicates mean of three readings; S.D.: Standard deviation. P value compared to Ibuprofen-β-CD i.e. significant C.E.: Complexation efficiency. CONCLUSION: This study has revealed that the improving the dissolution performance of Ibuprofen by its complexation with β-CD in presence of Leucine. Leucine showed a more pronounced effect on the enhancement of aqueous solubility and faster rate
  • 4. International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470 @ IJTSRD | Unique Paper ID – IJTSRD50151 | Volume – 6 | Issue – 4 | May-June 2022 Page 854 than binary complex. Phase solubility study of binary and tertiary systems shows that stability constant of ternary system is higher than that of binary system. Thus, addition of Leucine in tertiary complexes of β- CD beneficial in terms of improvement in CE, Rate of complex formation and enhancement of poorly water- soluble Ibuprofen. Ternary complex system was also found to give faster drug release as compared to pure Ibuprofen REFERENCES: [1] Drugbank (Hydrochlorothiazide). Available from: http://www.drugbank.ca/drugs/DB01050 [2] Pdf Materials and Instrument –Shodhganga [3] Aleem O., Kuchekar B., Pore Y., Late S., Effect of β- cyclodextrin and hydroxypropyl- βcyclodextrin complexation on physicochemical properties and antimicrobial activity of cefdinir, J. Pharm. Biomed. Anal, 47, 535-540, (2008). [4] Hassan H. A., Al-Marzouqi A. H., Jobe B., Hamza A., Ramadan G. A., Enhancement of dissolution amount and in vivo bioavailability of itraconazole by complexation with βcyclodextrin using supercritical carbon dioxide, J. Pharm. Biomed. Anal, 45, 243-250, (2007). [5] Araujo D., Tsuneda S., Cereda C., Carvalho., Prete P. et. al., Development and pharmacological evaluation of ropivacaine-2- hydroxypropyl – β-cyclodextrin inclusion complex, Eur. J. Pharm. Sci., 33, 60-71, (2008). [6] Brewster M. E., Vandecruys, R., Peeters J., Neeskens P., Verreck G., Loftsson T., Comparative interaction of 2- hydroxypropyl – β-cyclodextrin and sulfobutylether- βcyclodextrin with itraconazole: Phase- solubility behavior and stabilization of supersaturated drug solutions, Eur. J. Pharm. Sci., 34, 94-103, (2008) [7] Trandafirescu C., Gyeresi A., Aigner Z., Kata M., Epure C., Szabadai Z., Study of influence of citric acid on albendazole complexation with random methylated β – cyclodextrin, Farmacia, LVI, 1, 24-29 (2008) [8] Vica L., Bota S., Moisa C., Ganea M., Evaluation study of the inclusion complex of captopril - β – cyclodextrin, Farmacia, LV, 1, 93-97 (2007) [9] Drugbank (Hydrochoride) http://www.drugbank.ca/drug/DB00999. [10] Vyas A. Saraf S. SarafCyclfodextrin based noel drug delivery system. Jouranal of Inclusion Phenomena and Macrocyclic Chemistry. 2008, 62(1-2): 23-42. [11] PallaviDhekale, Anita Kulkarni, MohaSanodiya. Binary and ternary inclusion complexes of hydrochlorthiazide. International journal of pharmacy and pharmaceutical sciences. Vol 5. Issue 4’2013’718-722. [12] Aswathy S. Avadhni G S, Sujit S, ct al. Synthesis of β-cyclodextrinfunctionalized gold nanoparticles for the selective deteton of Pb2+ ions from aqueous solution. Frontiers of Mateials Science, 2012, 6(2): 168-175. [13] De Castr A D, Silva N P, Cury B S F, et al. A new approach to the granulation of β- cyclodextrin inclusion complexes. Chemical Engineering Journl, 2010, 164(2-3): 316-32. [14] Mohammadi A, Manteghian M, Mirzaei M. Effect of β-cyclodetrin on dissolution of methae in water. Chemical Engineerig Research and Design, 2011, 89(4): 421-427. [15] Bencini m, Ranucci E, Ferruti P, et al. Preparation and in vitro evaluation of the antiviral activity of the Acyclovir complex of a β-cyclodextrin / poly ( amidoamine) copolymer. Journal of Controlled Release, 2008, 126(1): 17-25. 10) Bonenfant D, Niquette P, Mimeault M, et al. UV-VIS and FTIR spectroscopic analyses of inclusion complxes of onylphenol and nonylphenolethoxyate with β- cyclodextrin. Water Research, 2009, 43(14): 3575-3581 [16] Li J S Xiao H N, Li J H, et al. Drug carrier system based on water- soluble cationic β- cyclodextrin polymers. International Journal of Pharmaceutics, 2004, 278(2): 329-342 [17] AbhijitPatil et al. “Effect of L-Arginine on Bicaitamidecomplexation with HPβCD”, Digest J and Biostructures, Vol-3, No2, Jun 2008, 89-98. [18] A. C. C Asbahr et al., “Binary Nanomaterialsternary inclusion complexes of Fensteride in HPβCD and polymers: Preparation and characterization, Elsevier, Bio. Org. Med. Chem17 (2007) 2718-2723. [19] Ahmed M. O, Ahmed S. M, et al., Complexation of Hydrochlorthiazide & Bendrofluazide with beta cyclodextrin in solution and in ground mixture, Saudi Pharma. J.:1996; 4; 1, 23, 28.