EVIDENCE FOR COMPLEX FORMATION OF IBUPROFEN WITH GO-GHRITA
HTML Full TextEVIDENCE FOR COMPLEX FORMATION OF IBUPROFEN WITH GO-GHRITA
- D. Bawankar *1, D. M. Sakarkar 1 and A. K. Dorle 2
Sudhakarrao Naik Institute of Pharmacy 1, Nagpur Road, Pusad – 445204, Maharashtra, India
Department of Pharmaceutical Sciences 2, RTM Nagpur University, Nagpur, Maharashtra, India
ABSTRACT: Present investigation provides evidence for complex formation of Ibuprofen (Ib) with Go-Ghrita (GG). Ibuprofen binary mixture in (1:0.5), (1:1), (1:2), (1:3) w/w proportions were prepared by adding to molten Go-Ghrita kept over a water bath at 65-70oC with continuous stirring. Organoleptic and Physico-chemical properties of GG (procured from Magan Sangrahalaya, Wardha) were as per the specifications given in Ayurvedic Pharmacopoeia (AP) and Indian Pharmacopoeia (IP). All proportions were subjected for FT-IR and in-vitro release behaviour (SGF, PH 1.2 for 2 Hrs and SIF, PH 6.8 for 7 Hrs) and on basis of it, optimized (1:1) w/w proportions were further analyzed and characterized for Differential Scanning Calorimetry, X-ray diffraction, Nuclear Magnetic Resonance and Scanning Electron Microscopy. Carbonyl stretching of isopropionic acid group to slight higher frequency 1.39 % cm-1 (increase) and (–C=O) linked (-OH) band stretching to slight lower frequency 1.09 cm-1 (decrease) shown in FT-IR spectra, supported by in-vitro release of Ibuprofen 99.16±0.17% of (1:1) w/w in sustenance form than remaining. Exclusion of polymorphic modification in X-RD, Slight lowering of 50C Tm and enthalpy change of 5.70 % (loss) in DSC, deviation in chemical shift (ranging from -0.041 to +0.030) as well as selective broadening of signals in NMR and entrapment of Ibuprofen crystals in Ib-GG binary mixture shown in SEM photographs, reflecting possible evidence for the formation of inclusion type complex between Ibuprofen and GG
Keywords: |
Ibuprofen, Go-Ghrita,
Ayurvedic Pharmacopoeia,
Physico-chemical, Inclusion complex, FT-IR., In-vitro release study, DSC, X-RD, NMR, SEM
INTRODUCTION: Go-Ghrita (GG), Sanskrit Indian word is common name for cow ghee. GG, along with other substances, composed of numerous saturated fatty acids like myristic, stearic, lauric, butyric, capric, caprylic and unsaturated fatty acids like linoleic, linolenic, vaccenic and arachidonic acids 1, leads to difficulty in proposing any single chemical structure of it.
Among these fatty acids, palmitic acid, a 16:0 saturated fatty acid, constitutes 29.95%, while oleic acid, which is 18: 1 monounsaturated acid with a double bond between 9-10 carbon atoms, is present to the extent of 27.42%2. GG has been shown to exhibit excellent wound healing property 3 as well as substantial anticonvulsant action 4.
A formulation containing some herbs and GG has been shown to exert remarkable memory enhancing activity 5 and patented in U.S. as an ointment base 6. Literature repleting with reports on use of GG in designing the sustenance release formulation 7, as well as few of its interaction study with NSAIDs like Acetaminophen 8-10 and Diclofenac sodium 11 with use of several sophisticated analytical techniques.
Keeping in mind all such few and rare interactions study of NSAIDs with GG, attempt has been made to examine the nature, type of interaction and complex formation of non reported Ibuprofen NSAID with GG (composing saturated and unsaturated fatty acids). To investigate such phenomenon one or more sophisticated analytical techniques like FT-IR, cumulative % Ibuprofen release from binary mixtures (1:0.5), (1:1), (1:2), (1:3) w/w proportions, DSC, X-rd, NMR and SEM were studied. In addition to this preliminary analysis of GG were carried out prior its used to confirm purity in binary mixture.
Ibuprofen12 – BCS class II drug, is most frequently used over-the-counter analgesics, due to its proven efficacy and low cost. Chemically, Ibuprofen (Fig. 1) is 2-[4-(2-methylpropyl) phenyl] propanoic acid, which has one chiral center, and thus there are two equal amounts of (R-) and sinister (S+) enantiomers.
FIG. 1: IBUPROFEN
MATERIALS:
Ibuprofen BP as a gift sample was kindly supplied by Zim Laboratories Ltd., Kalmeshwar, Nagpur. Go-Ghrita was purchased from Magan Sangrahalay, Wardha, India. All other chemicals and reagents used were of analytical grade and were procured.
Experimental Section:
Preliminary analysis of Go-Ghrita:
Organoleptic analysis:
Colour, Odour, Taste and Texture of GG sample was evaluated as described in AP13.
Physical characterization: Moisture content and Refractive index (reading at 400C) of GG sample was determined by the method described in AP13.
Chemical analysis:
Acid and Saponification values:
Acid and Saponification values of GG were determined as per the method described in AP13.
Iodine and Peroxide values:
Iodine and Peroxide values of GG were determined by pyridine bromide method and titration method as described in AP13.
Ester value of GG:
Ester value, difference between Saponification value and Acid value was determined as described in AP13.
Baudouin test for GG:
Sample response for this test is checked to verify purity and adulterant present in it, as described in AP13.
Free fatty acids (% oleic acid) and Unsaponifiable matter in GG:
Free fatty acids levels of GG sample was determined by the method as described in AP13 and IP14.
Preparation of sample:
To the molten GG kept over a water bath at 65-70oC an amount of Ibuprofen was added and uniformly dispersed by continuous stirring to prepare (1:0.5), (1:1), (1:2), (1:3) w/w proportions. The 1:0.5 to 1:3 w/w proportions were selected for observing minimize to maximize the interaction (if any) 15 involved in it. The fused mixtures were homogenized and allowed to cool slowly to room temperature with stirring.
Fourier Transform Infrared Spectroscopy (FTIR):
Fourier Transform Infrared Spectroscopy (FTIR) is a rapid analytical technique that measures vibrations of bonds within functional groups. FTIR spectral studies were carried out using FTIR spectrometer (Perkin Elmer Spectrum 2000, Norwalk, CT). Ibuprofen, GG and their binary mixtures (1:0.5), (1:1), (1:2), (1:3) w/w proportions were smeared onto KBr windows and the spectra were recorded from 500 to 3500/cm.
In-Vitro Ibuprofen Release Study: The % cumulative Ibuprofen release from the binary mixtures (1:0.5), (1:1), (1:2), (1:3) w/w proportions were studied in 900ml Simulated Gastric fluid (SGF), PH 1.2 without pepsin for first 2 Hrs and subsequent 7 Hrs in Simulated Intestinal fluid (SIF), PH 6.8 Phosphate buffer, stirred at 50 rpm, 37ºC ± 0.5ºC by USP - I (Rotating Basket type) method, VIII stations Dissolution Test Apparatus, Electrolab, Mumbai.
Scanning of Ibuprofen was carried out in both SGF and SIF between 200-400 nm and λmax was reported to be at 264 nm. Absorbance of standard calibration curve of Ibuprofen in SGF and SIF were analyzed, after adequate dilutions, at λmax 264 nm on UV Spectrophotometer (UV-1700; Pharmaspec, Shimadzu, Japan) equipped with UV probe software (2.01 version). Data was depicted in Microsoft excel and had correlation coefficient (R2) 0.997, 0.998 and equation of regression lines Y = 0.018X - 0.002 and Y = 0.020X - 0.001 respectively.
Drug content:
The percent drug content of each binary mixture were determined. Weighed accurately about 50 mg of Ibuprofen binary mixtures (1:0.5), (1:1), (1:2), (1:3) w/w proportions and dissolved in 20 ml of alcohol using the magnetic stirrer for 20 min. To the solution obtained, simulated gastric fluid or simulated intestinal fluid was added and volume was made upto 100 ml. It was then filtered through Whatman filter paper no. 42 and required dilutions were made and absorbance was taken at 264 nm.
Differential Scanning Calorimetry (DSC):
5-10 mg of Ibuprofen sample, GG and their 1:1 w/w binary mixture was weighed into pin holed platinum pans (TG/DTA instruments) and heated under dry nitrogen in 0 - 3400C scanning range at a rate of 100C/min. An empty pan was used as reference. Experiments were carried out in duplicate.
X-Ray Diffraction:
X-ray diffraction of Ibuprofen, GG and their 1:1 w/w binary mixture was carried out on a Rigaku Rotating Anode Diffractometer RUH3R (Tokyo, Japan). Measurement conditions were 40 kV, 30 mA current, at a scanning speed of 20/min, step size 0.02 and scanning range from 10–800 2Theta.
Nuclear Magnetic Resonance Spectroscopy:
NMR spectra (using Bruker DRX-300 MHz) for Ibuprofen, GG and their 1:1 w/w binary mixture were recorded in the solvent (CD3OD: CDCl3 3:1, v/v), using tetramethylsilane (TMS) as an internal standard. Samples (in solution form) were equilibrated in the probe 5 min prior each run.
Scanning Electron Microscopy:
Scanning electron microscopy of Ibuprofen, GG and their 1:1 w/w binary mixture mounted on scanning electron microscope stubs with double-sided carbon tape and observed under 370701-14, S-3700, Scanning Electron Microscope.
Statistical analysis:
The t-test was performed on all collected mean data obtained from physiological evaluation as well as dissolution studies. Significance was accepted at p≤0.0516.
RESULT AND DISCUSSION:
Physico-chemical analysis of GG:
Physico-chemical properties of GG given in Table 1 revealed the purity and adulterant free GG. All the tested parameter of GG passes the standards and limit given in Ayurvedic Pharmacopoeia13 and Indian Pharmacopoeia14 respectively.
TABLE 1: PHYSICO-CHEMICAL ANALYSIS OF GG
Sr. No | Physiological parameters of GG | Observations (Mean ± S.D.) | A.P. standards |
1. | Moisture content | 0.087% ± 0.0290 | NMT 0.5% |
2. | Refractive index | 42 ± 0.0090 | 40 – 45 |
3. | Acid value | 0.22 ± 0.0190 | NMT 0.15 - 0.25% |
4. | Saponification value | 190.74 ± 0.0210 | NMT 225 |
5. | Ester value | 189.79 ±0.0030 | NMT 225 |
6. | Iodine value | 25.88 ± 0.0199 | NMT 35 |
7. | Free fatty acids (% oleic acid) | 2.73 ± 0.0171 | NMT 3% |
8. | Unsaponifiable matter (%) | 0.4 % w/w ± 0.0025 | NMT 1.5% w/w |
9. | Baudouin test | No pink color formation | No pink colour |
10. | Peroxide value | 0.00 | Less than 0.5 |
All the determinations are carried out five times with significance (p≤0.05)
Fourier Transform Infrared Spectroscopy:
Fig. 2 showing FT-IR spectra of Ibuprofen (A), GG (B) and binary mixture of Ib with GG in different w/w proportions (C – F), reveling retention of characteristics bands as reported in literature 17, 19.
The ability of the GG to form a complex with Ibuprofen depends on the nature of the core-surface groups of GG (composed of saturated and unsaturated fatty acids), electrostatic interactions between the GG and the Ib, and the ability of the Ib to form a conjugate with the GG through chemical bonding. One might expect that the Ib with the carboxylic group may form a complex with surface unsaturated -C=C- fatty acids group (may exists as dimer involving hydrogen bonding) 19 of GG and may physically encapsulate the Ib.
Pure Ibuprofen (Fig. 2A) shows a strong carbonyl band absorbance at 1718.39 cm−1, which corresponds to the carboxyl acid group (COOH) where as other smaller peaks in the region 1500–500 cm−1 are contributions from the benzene ring16. FTIR spectrum of all binary mixture (Fig. 2 C - F) 1:0.5, 1:1, 1:2, 1:3 w/w shows disappearance of strong carbonyl band at 1718.39 cm−1 of ibuprofen and shifted to slight higher frequency 1742.93 cm−1 (i.e. 1.39 % cm-1 increase), as well as (–C=O) linked (-OH) band stretching to slight lower frequency 2921.29 cm-1 (i.e. 1.09 cm-1 decrease) band due to observed band respective at 1742.93 cm-1 and 2921.49 cm-1 (Fig. 2B) of carboxylic and OH group of saturated or unsaturated fatty acid 8, 9 present in GG.
FIG. 2: FT-IR SPECTRA OF A) IBUPROFEN, B) GG, C) BINARY MIXTURE OF IB-GG 1:0.5 w/w, D) 1:1 w/w, E) 1:2 w/w, F) 1:3 w/w PROPORTION.
TABLE 2: FTIR SPECTRUM INTERPRETATION OF IBUPROFEN
Characteristic peaks | Ibuprofennnn | 1:0.5 | 1:1 | 1:2 | 1:3 | % Stretching |
Carbonyl stretchingof isopropionic acid group | 1718.39 cm-1 | 1742.71 cm-1 | 1742.57 cm-1 | 1742.55 cm-1 | 1742.60 cm-1 | 1.39 cm-1 (Increase) |
(-OH) stretching linked to(–C=O) | 2954.02 cm-1 | 2921.57 cm-1 | 2921.29 cm-1 | 2921.28 cm-1 | 2921.37 cm-1 | 1.09 cm-1 (Decrease) |
Drug content and % Ibuprofen release:
Binary mixtures of various w/w proportions were subjected for Ibuprofen determination and 1:1 w/w found to be highest 98.85± 0.07 in SGF, 98.97± 0.13 in SIF observed slightly less (Table 3) in 1:0.5, 1:2, 1:3. The strength and stability of the Ib-GG complex was examined using in vitro release study.
Fig. 3 represents more uniform and sustenance zero order release 99.16±0.17 (Table 4) of Ibuprofen with R2 value 0.9931 (Table 5) from 1:1 binary complex in both SGF and SIF, represents the efficacy, integrity and entrapment of Ib in IB-GG binary mixture. The order of % cumulative Ibuprofen release is 1:1 > 1:0.5 > 1:2 > 1:3.
FIG. 3: CUMULATIVE % IBUPROFEN RELEASE FROM (1:0.5), (1:1), (1:2), (1:3) W/W PROPORTIONS.
TABLE 3: PERCENT DRUG CONTENT OF IBUPROFEN FROM BINARY MIXTURES
Sr.No. | Binary mixturesw/w proportion | Drug content* (%) | |
SGF | SIF | ||
1. | 1:0.5 | 95.15± 0.27 | 96.52± 0.16 |
2. | 1:1 | 98.85± 0.07 | 98.97± 0.13 |
3. | 1:2 | 96.84± 0.23 | 97.04± 0.31 |
4. | 1:3 | 97.45± 0.16 | 96.07± 0.18 |
(*Represents mean ± S. D.) (n=3)
TABLE 4: CUMULATIVE % IBUPROFEN RELEASE OF VARIOUS BINARY MIXTURES
Sr.No. | Medium | Time (Hr) | Cumulative % Ibuprofen release* | |||
1:0.5 | 1:1 | 1:2 | 1:3 | |||
1. | 0.1N HCl, PH 1.2 | 1 | 7.63±0.81 | 7.13±1.81 | 7.06±0.71 | 6.8±0.72 |
2. | 2 | 13.63±1.72 | 12.13±0.82 | 11.23±2.73 | 10.8±2.28 | |
3. | Phosphate Buffer, PH 6.8 | 3 | 41.23±0.67 | 39.8±0.71 | 37.28±2.83 | 35.97±0.92 |
4. | 4 | 55.89±1.72 | 49.82±0.62 | 48.92±1.04 | 44.71±1.29 | |
5. | 5 | 67.22±1.87 | 65.34±0.72 | 59.05±0.27 | 57.86±1.23 | |
6. | 6 | 89.51±1.91 | 72.16±2.82 | 70.99±1.83 | 76.19±1.91 | |
7. | 7 | 99.27±0.71 | 87.27±0.74 | 81.67±0.26 | 79.58±0.99 | |
8. | 8 | 99.25±0.81 | 99.36±0.17 | 91.47±1.98 | 88.74±2.82 |
(*Represents mean ± S.D.)(n=3)
TABLE 5: RELEASE KINETICS OF VARIOUS BINARY MIXTURES
Release Model | 1:0.5 | 1:1 | 1:2 | 1:3 |
R2 | R2 | R2 | R2 | |
Zero Order | 0.988003386 | 0.993106749 | 0.992887086 | 0.990536068 |
First Order | 0.87895189 | 0.87436741 | 0.87703903 | 0.88385852 |
Higuchi Release | 0.94625087 | 0.94751185 | 0.94934934 | 0.94549569 |
Corse Mayer Release | -0.217129721 | -0.245366501 | -0.258414266 | -0.256524447 |
Hixson Crowell Model | 0.953695555 | 0.943430824 | 0.943941692 | 0.949910273 |
Differential Scanning Calorimetry:
The DSC thermograms of Ibuprofen, GG and Ib-GG 1:1 w/w proportions are presented in Fig. 4. The following general results can be derived from Table 6, 7 the melting temperature of binary systems (Fig.4C) are lower than those of single Ibuprofen (Fig.4A). The thermogram of Ibuprofen-GG 1:1 w/w records two sharp endothermic peaks corresponding to their melting point with onset at 76.80C and 263.20C respectively along with approximately 5.70 % loss in enthalpy (∆Hobserved) in comparison to (∆Hcalculated) values of system, suggesting the possibility of interaction20, 21.
FIG. 4: DSC OF A) IBUPROFEN, B) GG, C) BINARY MIXTURE OF IB-GG 1:1 w/w PROPORTION.
TABLE 6: THERMAL PARAMETERS OF IBUPROFEN, GG AND BINARY MIXTURE 1:1 w/w PROPORTIONS
Sr. No. | Type | Tpeak (0C) | ∆H (J/g) |
1 | Ibuprofen | 81.5 | 162 |
2 | GG | 52.9 | 26.7 |
3 | Ib-GG 1:1 | 76.8 | 42.7 |
X-Ray Diffraction:
Almost no change was detected in their diffraction pattern of crystalline nature of Ibuprofen (Fig. 5) as well as GG. In the diffraction pattern of the Ib – GG binary mixture, Ibuprofen and GG retained their respective peaks at their positions.
Nuclear Magnetic Resonance Spectroscopy:
NMR spectra of Ibuprofen (Fig. 6A), GG (Fig. 6B) and Ib-GG 1:1 w/w proportion (Fig. 6C) are presented with chemical shift records in Table 8. Ib-GG 1:1 w/w proportion (Fig. 6C) showed more pronounced changes in chemical shift values of different protons (2H, 4-7H, 9H, 10-13H) ranging from -0.041 to +0.030 as well as selective broadening of 9H proton, confirming possible interactions. Interaction between the two substances relies on the observation of selective line broadening and/or chemical shift displacements of H-NMR spectral signals of a substance bonded with other 11, 22.
TABLE 7: THERMAL PARAMETERS OF IB-GG 1:1 W/W PROPORTIONS
Binary Mixture | 1ST Transition | 2ND Transition | ∆Hcal (J/g) | ∆Hobs (J/g) | ∆H %/Result | ||
Tpeak (0C) | ∆H (J/g) | Tpeak (0C) | ∆H (J/g) | ||||
Ib-GG 1:1 w/w | 76.8 | 42.7 | 263.2 | 119 | 170.47 | 161.70 | 5.70(loss) |
FIG. 5: X- RD OF A) IBUPROFEN, B) GG, C) BINARY MIXTURE OF IB-GG 1:1 W/W PROPORTION.
FIG. 6: NMR OF A) IBUPROFEN, B) GG, C) BINARY MIXTURE OF IB-GG 1:1 W/W PROPORTION.
TABLE 8: CHEMICAL SHIFTS (δ) PPM OF PROTONS IN IBUPROFEN AND IB-GG % w/w PROPORTIONS
H/H | Ppm (δ) | ∆δ =(δ1) - (δ2) | |
Ib (δ1) | Ib-GG (δ2) | ||
2H | 3.745 | 3.704 | - 0.041 |
4,5,6,7H | 7.228 | 7.221 | - 0.007 |
9H | 2.470 | 2.500 | + 0.030 |
10H | 1.941 | 1.906 | - 0.035 |
11,12H | 1.001 | 1.013 | + 0.012 |
13H | 1.631 | 1.610 | - 0.021 |
Scanning Electron Microscopy:
Scanning electron micrographs of crystals of Ibuprofen appear stick shaped and particle surface is quite regular as illustrates in Fig. 7 (A) at 100X magnification. In the admixture of Ibuprofen with GG, the open lattice matrix or cage like crystal structures of GG Fig. 7 (B) entrapped the stick shaped Ibuprofen crystals with them (inclusion type complex)23; some of them lost their crystal habit while the habit of remaining was modified in the presence of GG, highlighted by arrow in Fig. 7 (C). The degree of entrapped stick shaped Ibuprofen crystals in open lattice matrix or cage like crystal structures of GG may be the determining factor in the diffusion or dissolution of Ibuprofen.
FIG. 7: SCANNING ELECTRON MICROSCOPY AT A MAGNIFICATION OF 100X A) IBUPROFEN, B) GG, C) BINARY MIXTURE OF IBUPROFEN WITH GG (MARKED ARROW SHOWING IBUPROFEN CRYSTALS GET TRAPPED IN CAGE STRUCTURES OF GG)
CONCLUSION: In present investigation, we report the evidence of complex formation of Ibuprofen with Go-Ghrita. The FT-IR spectrum of binary mixtures detected characteristics increase in strong carbonyl band and decrease in (–C=O) linked –OH band. More uniform and sustenance zero order release of 1:1 w/w from in-vitro dissolution study (render its selection for optimization), % loss in enthalpy (∆Hobserved) in comparison to (∆Hcalculated) values of DSC system, suggesting the possibility of interaction. Moreover such complexation phenomenon can be verified by X-RD, NMR and SEM. Retention of respective peaks at their positions in 1:1 w/w binary mixture, revealed crystalline nature of Ibuprofen minimizes the possibility of polymorphic modification in X-RD. Deviation in chemical shift as a slight displacement of proton as well as selective broadening of signals in 1:1 w/w NMR, confirming possible interaction between Ibuprofen and fatty acids present in GG, substantiated by SEM photographs.
SEM further elucidated entrapment of ibuprofen crystal structure in open lattice matrix or cage like crystal structures of GG suggesting inclusion type complex. However, an interesting part is, such sustenance release inclusion complex of Ibuprofen with GG (or other NSAIDs which may form a complex with GG) may be useful in increasing the oral bioavailability or comparing such complex concentration in various biological fluids in experimental animals is under study.
ACKNOWLEDGEMENTS: The authors gratefully acknowledge the useful discussion with Dr. Arun K. Misra, Scientist, Cadila Pharmaceuticals Ltd., Dholka, Ahmedabad, India. In addition, the authors would like to thank Mr. Vijay Pudke, Head, Quality Control Department, Zim Laboratories Ltd., Kalmeshwar, Nagpur, (M.S.), India for kindly supplying Ibuprofen gift sample.
REFERENCES:
- Rangappa KS and Achaya KT: Indian Dairy Products, Bombay. Asia Publishing House. 1974; 1- 386.
- Ramamurthy MK and Narayanan KM: Fatty acid compositions of buffalo and cow milk fats by GLC. Milchwissenschaft. 1971; 26: 693-697.
- Datta HS, Mitra SK and Patwardhan B: Wound healing activity of topical application forms based on Ayurveda. eCAM. 2009; 1-10.
- Achliya, GS, Wadodkar SG and Dorle AK: Evaluation of sedative and anticonvulsant activities of Unmadnashak Ghrita. Ethnopharmacol. 2004; 94(1): 77-83.
- Achliya GS, Wadodkar SG and Dorle AK: Evaluation of C.N.S. activity of Brahmi Ghrita. Indian Journal of Pharmacology. 2005; 37(1): 33-38.
- Shah E: Phamaceutial/ Medicinal formulation containing Cow’s ghee as a vehicle. U.S. Patent. 1997; 5693327.
- Sakarkar DM, Jaiswal SB, Dorle AK. And Deshmukh VN: Application of cow’s ghee as hot melt coating agent in the design of sustained release pellets. International Journal of Pharm Tech and Research. 2009; 1(4): 1167-1172.
- Misra AK, Misra M, Panpalia GM and Dorle AK: Thermoanalytical and microscopic investigation of interaction between Paracetamol and fatty acid crystals. J. Macromol Sci. PAC. 2007; 44: 685-690.
- Misra AK, Misra M, Panpalia GM and Dorle AK: Interaction study of Paracetamol with saturated (Capric) and unsaturated (Oleic) Fatty acids. Pharmaceutical Development and Technology. 2007; 12: 1-6.
- Misra AK, Misra M, Panpalia GM and Dorle AK: Investigation of mechanism of release of Acetaminophen from cow’s ghee and its saturated fatty acids. J. Pharm. Res. 2008; 7: 220.
- Misra M, Misra AK, Zope P, Panpalia GM and Dorle AK: Interaction study of NSAIDs with cow’s ghee and its fatty acids by NMR spectroscopy. J. of Global Pharma Technology. 2010; 2(8): 24-29.
- British Pharmacopoeia, Volume-II, The Department of Health, Social Services and Public Safety; British Pharmacopoeia Commission Office, London, 2009; A 1-5.
- The Ayurvedic Pharmacopoeia of India, Part - I, Volume - VI , 1st edition, Published by government of India, Ministry of Health & Family Welfare, Department of Ayurveda, Yoga & Naturopathy, Unani, Siddha & Homeopathy [Ayush], New Delhi. 2007; 204 - 210.
- Indian Pharmacopoeia, Volume-I, Published by The Indian Pharmacopoeia Commission, Ghaziabad, on behalf of Government of India, Ministry of Health and Family Welfare, New Delhi. 2007; 89-90.
- Akers MJ: Preformulation testing of solid oral dosage forms. Can. J. Pharm. 1976; 11: 1-10.
- Townend J: Practical Statistics for Environmental and Biological Scientists. England, John Wiley and Sons Ltd. 2002; 270-276.
- Nakanishi K and Solomon, PH: Infrared Absorption Spectroscopy. Holden-Day, Inc.: San Francisco. 15th, 977.
- Kolhe P, Misra E, Kannan RM, Kannan S and Lieh-Lai M: Drug Complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers. International Journal of Pharmaceutics. 2003; 259: 143–160.
- Silverstein RM and Webster FX: Spectrometric Identification of Organic Compounds; VI Ed., John Wiley & Sons, Inc.: New York, 1998, 95–97.
- Hamed H, Shattawy El, Garnet EP and Kildsig DO: Aspartame-Direct Compression Excipients: Preformulation Stability Screening Using Differential Scanning Calorimetry. Drug Dev. Ind. Pharm. 1981; 7(5): 605-619.
- Loftsson T, Olafsdottir BJ, Frioriksdottir H and Jonsdottir S: Cyclodextrin complexation of NSAIDs: Physiochemical considerations. Eur. J. Pharm. Sci. 1993; 1: 95–101.
- Arancibia JA and Escandar GM: Complexation study of diclofenac with β-cyclodextrin and Spectrofluorimetric determination. Analyst. 1999; 124: 1833-1838.
- Francesco B, Brunella C, Maria IL, Rotonda AM and Fabiana Q: Diclofenac/β-Cyclodextrin Binary Systems: A Study in Solution and in the Solid State. Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2003; 46: 179–185.
How to cite this article:
Bawankar RD, Sakarkar DM and Dorle AK: Evidence for Complex Formation of Ibuprofen with Go-Ghrita. Int J Pharm Sci Res 2015; 6(4): 1771-78.doi: 10.13040/IJPSR.0975-8232.6(4).1771-78.
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Article Information
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1771-1778
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English
Ijpsr
R. D. Bawankar *, D. M. Sakarkar and A. K. Dorle
Sudhakarrao Naik Institute of Pharmacy, Nagpur Road, Pusad (M.S.), India
rambawankar2008@rediffmail.com
22 August, 2014
23 November, 2014
27 December, 2014
10.13040/IJPSR.0975-8232.6(4).1771-78
01 April, 2015