aug 2016 - pharmaerudition.orgpharmaerudition.org/contentpaper/2016/aug 16 _12-19_.pdf · namely...

Aug 2016

Vol: 06 Issue: 02(12-19)

International Journal of Pharmaceutical Erudition

www.pharmaerudition.org Aug 2016, 6(2), 12-19 12 | P a g e

ISSN 2249-3875

Research Paper

Solid as Solvent” - Novel Spectrophotometric Analysis of Piroxicam Tablets UsingSolids (Eutectic Liquid of Phenol and Metformin Hydrochloride) As Solubilizing

Agents (Mixed Solvency Concept)R K Maheshwari, Sunil Goyal*, Rohit Adhav, Priyanka Vaswani

Department of Pharmacy, Shri G S Institute of Technology and Science, Indore 452003, Madhya Pradesh,India

Solubility enhancement of the drugs having poor solubility is a difficult task in several cases in pharmacyfield. The present investigation is an attempt to show that solids can also be wisely used to act as solventprecluding the use of organic solvents. In the present study, a eutectic liquid (PMHCl 41) obtained bytriturating phenol crystals and metformin hydrochloride in 4:1 ratio on weight basis was employed to extract(dissolve) the piroxicam drug from fine powder of tablets. Distilled water was used for dilution purpose tocarry out spectrophotometric estimation at 358 nm without utilizing any organic solvent. The solubility ofpiroxicam in distilled water at room temperature was found to be 0.4 mg/ml while the solubility in PMHCl 41liquid was more than 125 mg per ml (of PMHCl 41). Proposed method is novel, free from organic solvent,accurate and reproducible. The accuracy, reproducibility and precision of the proposed method wereconfirmed by recovery studies and statistical data. The presence of tablet excipients, phenol and metforminhydrochloride did not interfere in the spectrophotometric estimation at 358 nm. Phenol and metforminhydrochloride do not interfere above 300 nm.

Keywords – Piroxicam, mixed-solvency concept, phenol, metformin hydrochloride, spectrophotometricanalysis, eutectic liquid.

INTRODUCTIONCosolvency, hydrotropy, micellar solubilization,complexation, pH modification and salt formationare the most frequently employed commontechniques of solubility enhancement. A noveltechnique of solubility enhancement by use ofmixed solvency concept has been proposed byMaheshwari1-6. All the substances (whetherliquids, gases or solids) have solubilizing power.Innumerable solvent systems may be developedusing mixed solvency concept. By application ofmixed solvency concept7-17, the drug loading in

various pharmaceutical formulations, includingNDDS, may be improved and by combining theexcipients in appropriate amounts, synergisticsolvent actions and additive solvent actions canbe obtained and also the problem of toxicity issuedue to high concentration of a solvent for desiredsolubility of the drug can be solved. Maheshwari6

utilized mixed solvency concept to potentiate thesolvent character of a weaker solvent. In thisresearch work it has been shown that a weakersolvent can be made a strong solvent by

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ISSN 2249-3875

incorporation of a solid solubilizer. The solubilityof frusemide in ethanol was enhanced aboutthree fold in the presence of 15% w/vniacinamide (a solid solubilizer). Frusemide issparingly soluble in ethanol and pharmacopoeialmethod requires dimethyl formamide (a class IIorganic solvent) for titrimetric analysis offrusemide bulk drug. In this research work, 15%w/v solution of niacinamide in ethanol wassuccessfully employed to carry out titrimetricanalysis of frusemide bulk drug, giving anecofriendly method of analysis because ethanolis a class III organic solvent (relatively safe incomparison to dimethyl formamide). Mixedsolvency concept has been nicely employed forthe improvement of the solubilities of a largenumber of poorly soluble drugs1-29.

Several organic solvents are employed forspectrophotometric analysis of dosage forms ofpoorly water soluble drugs. Methanol, ethanol,chloroform, acetonitrile, toluene, carbontetrachloride, dichloromethane, dimethylformamide, ethyl acetate, acetone and hexaneare the most common examples of suchsolvents. High cost, toxicity and pollution areserious drawbacks of organic solvents. Thepresent investigation is an attempt to show thatsolids can also be wisely employed forspectrophotometric estimation of poorly solubledrugs without using the organic solvents.

Present study describes the application ofsolvent character of eutectic liquid (PMHCl 41) oftwo solid solubilizers, namely, phenol andmetformin hydrochloride for spectrophotometricestimation of piroxicam tablets. Piroxicam hasgot poor solubility in distilled water while veryhigh solubility in a eutectic liquid of two solids,namely phenol and metformin hydrochloride.Phenol and metformin hydrochloride wereemployed in 4:1 ratio to give eutectic liquid,PMHCl 41. This liquid was used to act as solventto extract out the drug, piroxicam, from the finepowder of its tablets for spectrophotometricestimation at 358 nm. Distilled water was usedfor dilution purpose. The solubility of the drug indistilled water is 0.4 mg/ml at room temperaturewhile the approximate solubility in PMHCl 41 ismore than 125 mg/ml. Proposed method is novel,accurate, rapid and free from toxicity of organicsolvents and reproducible. Recovery studies andstatistical data proved the accuracy,reproducibility and precision of the proposedmethod. There was no interference of tabletexcipients, phenol and metformin hydrochlorideat 358 nm.Materials and methodsPiroxicam bulk drug sample was a generous giftby M/S Shree Pharmaceuticals, Indore (India).Metformin hydrochloride was generous gift fromM/S IPCA Laboratories Limited, Ratlam (India).




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Commercial tablets of piroxicam (Nesprex-DT ofNestor Pharmaceuticals Limited, Goa andPiroxits DT of Intas Pharmaceuticals Limited,Ahmedabad) were procured from the localmarket. All other chemicals used were ofanalytical gradeA Shimadzu-1700 UV visible spectrophotometerwith 1 cm matched silica cells was used forspectrophotometric analysis.

Preparation of eutectic liquid - Phenol andmetformin hydrochloride were triturated in 4:1ratio on weight basis to obtain a eutectic liquid(PMHCl 41).

Calibration curve- Accurately weighed 50 mg ofpiroxicam standard drug sample was transferredto a 500 ml volumetric flask. Eutectic liquid,PMHCl 41 (10 ml) was transferred to thisvolumetric flask and the volumetric flask wasshaken for few minutes to obtain a clear solution.Now 400 ml of distilled water was added and theflask was shaken for about 5 minutes to get aclear solution. Sufficient of distilled water wasadded to make up the volume to 500 ml. In thisway a stock solution of drug (100 µg/ml) wasobtained. After suitable dilutions with distilledwater, the standard solutions containing 5, 10,15, 20 and 25 µg/ml of drug were prepared.Calibration curve was obtained by using theabsorbances of these standard solutions,measured against their respective reagent blanks

at 358 nm.

Preliminary solubility studiesThe equilibrium solubility of piroxicam drug indistilled water was determined. For this, excessamount of drug sample was added to a 25 mlcapacity vial containing distilled water. Afterputting the vial cap and applying the aluminiumseal properly, the vial was shaken mechanicallyfor 12 hours at room temperature in an orbitalflask shaker (Khera Instrument Pvt. Ltd., India).The vial was kept undisturbed for 24 hours.Then, the filtration was carried out usingWhatmann filter paper # 41. The filtrate wasappropriately diluted with distilled water and theabsorbance was noted at 358 nm. The result ofsolubility was computed using the calibrationcurve.

Then, the approximate solubility of drug wasdetermined in the eutectic liquid. For this, 1 ml ofPMHCl 41 was taken in a 10 ml volumetric flaskand the weight of this flask was noted. About 5mg of drug was added in the volumetric flask andthe flask was shaken to solubilize the drug. Assoon as a clear solution was obtained, againabout 5 mg of drug was transferred to the flaskand the flask was shaken to solubilize the drug.Same procedure was repeated till the eutecticliquid was nearly saturated with the drug (at thisstage, slight turbidity was observed). Then, thefinal weight of the flask was noted. Difference in




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these two weights provided the approximateamount of drug solubilized by 1 ml of PMHCl 41.In this way, the approximate solubility of drug inPMHCl 41was determined.Proposed method of analysisIn order to determine the drug content, twentytablets of tablet formulation I were weighedaccurately. With the help of pestle and mortar,the tablets were crushed to get a fine powder.The powder of tablets equivalent to 50 mgpiroxicam was transferred to a 500 ml volumetricflask. Ten ml of PMHCl 41 liquid was added inthe flask and the flask was shaken continuouslyfor 10 minutes manually. This step ensured thecomplete dissolution of piroxicam drug (presentin the tablet powder taken) in the 10 ml of PMHCl

41 liquid. Then, about 400 ml of distilled waterwas added in the flask and the flask was shakenfor 5 minutes. This step helps to retain the drug(piroxicam), phenol and metformin hydrochloridein the solution form. Then, the volume was madeup to 500 ml with distilled water. After filtrationthrough Whatmann filter paper # 41 (discardingthe first few ml of the filtrate), 10 ml of the filtratewas diluted with distilled water up to 50 ml andthe absorbance was noted at 358 nm against thereagent blank.This procedure was applied thrice (n=3). Exactlythe same procedure was used for assay of tabletformulation II. The drug contents weredetermined using the calibration curve and theresults of analysis were recorded in Table 1.

Table I: Analysis data of piroxicam tablet formulations with statistical evaluation (n=3)Tabletformulation

Label claim(mg/tablet)

Percent drug estimated(mean ± SD)

Percent coefficientof variation

Standard error

I 20 101.39 ± 1.419 1.399 0.819

II 20 99.57±1.914 1.922 1.105

Table 2: Results of recovery studies with statistical evaluation (n=3)Tabletformulation

Drug in pre-analyzed tabletpowder (mg)

Amount ofstandard drugadded (mg)

% Recoveryestimated(mean ± SD)

Percent coefficientof variation

Standarderror

I 50 15 100.41±0.992 0.988 0.573

I 50 30 101.74±1.290 1.268 0.745

II 50 15 99.81 ±1.082 1.084 0.625

II 50 30 101.31±1.012 0.999 0.584




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Results and DiscussionThe solubility of piroxicam in distilled water atroom temperature was found to be 0.4 mg/ml.The approximate solubility of piroxicam in PMHCl41 was more than 125 mg per ml (of PMHCl 41).It is evident from table 1, that the percent drugestimated in tablet formulation I and II were101.39±1.419 and 99.57±1.914, respectively.The values are very close to 100.0, indicating theaccuracy of the proposed analytical method.Small values of statistical parameters viz.standard deviation, percent coefficient ofvariation and standard error (table 1) furthervalidated the method. Further, table 2 shows thatthe range of percent recoveries varied from99.81±1.082 to 101.74±1.290 which are againvery close to 100.0, indicating the accuracy of theproposed method. Proposed analytical techniqueis further supported by significantly low values ofstatistical parameters viz. standard deviation,percent coefficient of variation and standard error(table 2).ConclusionIn the present study, a eutectic liquid obtained bytriturating phenol crystals and metforminhydrochloride in 4:1 ratio on weight basis wasemployed to extract (dissolve) piroxicam drugfrom fine powder of its tablets. Dilution was madewith distilled water to carry outspectrophotometric estimation at 358 nm without

the help of organic solvent. Proposed method isnovel, rapid, free from toxicity of organic solvent,accurate and reproducible. Recovery studies andstatistical data proved the accuracy,reproducibility and precision of the proposedmethod. The presence of phenol, metforminhydrochloride and the tablet excipients did notinterfere in the spectrophotometric estimation at358 nm. Phenol and metformin hydrochloride donot interfere above 300 nm.AcknowledgementWe are thankful to M/S Shree Pharmaceuticals,Indore (India) and M/S IPCA LaboratoriesLimited, Ratlam (India) for gift samples ofpiroxicam bulk drug and metformin hydrochloridebulk drug, respectively.

REFERENCES1. Maheshwari RK. “Mixed-solvency approach”-Boon for solubilization of poorly soluble drugs.Asian Journal of Pharmaceutics 2010; Jan-March: 60-63.2. Maheshwari RK. Solubilization of ibuprofenby mixed solvency approach. The IndianPharmacist 2009; 8(87): 81-84.3. Maheshwari RK. “Mixed- solvency” – A novelconcept for solubilization of poorly water-solubledrugs. Delving J. Tech. Eng. Sci. 2009;1(1): 39-43.4. Rajesh Kumar Maheshwari, “Solid as




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solvent”, Novel spectrophotometric analysis ofsatranidazole tablets using phenol as solvent.The Indian Pharmacist 2014, vol. XII, 37-40.5. Maheshwari RK. “Solid as solvent”-Novelspectrophotometric analysis of tinidazole tabletsusing melted phenol as solvent. Asian Journal ofPharmaceutical Research 2015;5(1):21-24.6. Maheshwari RK. Potentiation of solventcharacter by mixed solvency concept: A novelconcept of solubilization. Journal of PharmacyResearch 2010; 3(2): 411-413.7. Maheshwari RK, Shilpkar R. Formulationdevelopment and evaluation of injection of poorlysoluble drug using mixed solvency concept.International Journal of Pharma and Biosciences2012; Vol. 3 / Issue I/ Jan-Mar: 179-189.8. Maheshwari RK, Rajagopalan R. Formulationand evaluation of paracetamol syrup made bymixed-solvency concept. Der Pharmacia Lettre2012; 4(1): 170-174.9. Soni LK, Solanki SS, Maheshwari RK.Solubilization of poorly water soluble drug usingmixed solvency approach for aqueous injection.British Journal of Pharmaceutical Research2014; 4(5): 549-56810. R. K. Maheshwari, Naveen Chaklan,Sugandha Singh, Novel pharmaceuticalapplication of mixed solvency concept fordevelopment of solid dispersions of piroxicam,European Journal of Biomedical and

Pharmaceutical Sciences 2015;1(3):578-591.11. Maheshwari RK, Karawande VU, Applicationof novel concept of mixed solvency in the designand development of floating microspheres offurosemide. International journal of Pharmacyand Pharmaceutical Sciences 2013, vol.15: 167-195.12. Agrawal A, Maheshwari RK. Formulationdevelopment and evaluation of in situ nasal gel ofpoorly water soluble drug using mixed solvencyconcept. Asian Journal of Pharmaceutics 2011;5(3); 131-140.13. Prashant B, Rawat S, Mahajan YY, GalgatteUC, Maheshwari RK. Formulation developmentand evaluation of aqueous injection of poorlysoluble drug made by novel application of mixedsolvency concept. International Journal of DrugDelivery 2013; vol: No. 2: 152-166.14. Maheshwari Y, Mishra DK, Mahajan SC,Maheshwari P, Maheshwari RK, Jain J. Novelpharmaceutical application of mixed solvency inthe formulation development of syrups (liquid oralsolutions) of poorly water-soluble drugs.International Journal of Pharmacy 2013; 3(4):753-758.15. Chandna C, Maheshwari RK. Mixed solvencyconcept in reducing surfactant concentration ofself emulsifying drug delivery systems ofcandesartan cilexetil using D-optimal mixturedesign. Asian Journal of Pharmaceutics 2013,




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April-June issue: 83-91.16. Maheshwari RK, Rajagopalan R. Formulationand evaluation of tinidazole syrup made bymixed-solvency concept. Der Pharmacia Lettre2011; 3(6): 266-271.17. Love Kumar Soni, Shailendra Singh Solanki,Rajesh Kumar Maheshwari. Studies on mixedsolvency concept in formulation development oforal solution (syrup) of poorly water soluble drug,Journal of Harmonized Research in Pharmacy2015;4(4):305-315.18. R. K. Maheshwari, A. Fouzdar, “Solid assolvent” - Novel approach for spectrophotometricestimation of solid dosage form of nalidixic acidusing solids (eutectic liquid of phenol andniacinamide) as solubilizing agents (mixedsolvency concept), European Journal ofBiomedical and Pharmaceutical Sciences 2014;1(3):424-430.19. Rajesh Kumar Maheshwari, Ravish Jain,Priya George. Formulation development andevaluation of controlled release tablets oflamotrigine using mixed solvency concept,Bulletin of Pharmaceutical Research2015;5(1):14-19.20. Maheshwari RK. “Solid as solvent”- Novelspectophotometric analysis of norfloxacin tabletsusing phenol as solvent”. International Journal ofCurrent Pharmaceutical Research 2014;6:76-78.

21. Maheshwari RK, Upadhyay N, Jain J, PataniM, Mathuria KC. New spectrophotometricestimation of naproxen tablet formulationemploying mixed solvency concept (at 331 nm).International Journal of Pharmacy andTechnology 2011; Vol. 3/ Issue No. 4/ 3618-3623.22. Maheshwari RK, Gupta S, Gharia A, GargSK, Shilpkar R. Simple eco-friendlyspectrophotometric estimation of tinidazoletablets by application of mixed-solvencytechnique. Bulletin of Pharmaceutical Research2011; 1(1): 22-25.23. Bhawsar N, Maheshwari RK, Ansari A,Saktawat Y. New spectrophotometric estimationof gatifloxacin in the tablets using mixed solvencyapproach. International Journal ofPharmaceutical Science 2011; Vol. 2/ Issue 2/Apr-Jun: 270-274.24. Vijayranga G, Deveswaran R, Bharath S,Basavraj BV, Madhavan V. Development of ananalytical method for spectrophotometricestimation of ketoprofen using mixed solvencyapproach. International Journal ofPharmaceutical Sciences and Research 2012;4:1053-1056.25. Maheshwari RK, Upadhyay N, Jain J, PataniM, Pandey R. New spectrophotometric analysisof gatifloxacin tablets utilizing mixed solvency




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concept (at 288 nm). Der Pharmacia Lettre 2012;4(1): 1-4.26. Maheshwari RK, Putliwala M, Padiyar A.Novel approach for spectrophotometricestimation of naproxen in tablet dosage formusing solids (eutectic liquid of phenol andniacinamide) as solubilizing agent (mixedsolvency concept). Asian Journal ofPharmaceutical Research, 2015;5(1):25-28.27. Maheshwari, R. K., Padiyar,A, Putliwala, M.,Utilization of mixed solvency technique inspectrophotometric analysis of cefixime trihydratetablets, International Journal of Pharmaceutical

Research and Analysis 2015;5(1):01-03.28. Rajesh Kumar Maheshwari, Masheer AhmedKhan, Nupur Maheshwari, Neelesh Maheshwari,“Solid as solvent”-Novel spectrophotometricanalytical method for metronidazole tablets usingsolids (eutectic liquid of phenol and niacinamide)as solubilizing agents (mixed solvency concept).Research Journal of Pharmacy and Technology2016;9(6):705-708.29. Maheshwari RK. “Solid as solvent”-Novelspectrophotometric analysis of frusemide tabletsusing phenol as solvent. Bulletin ofPharmaceutical Research 2014;4(2):104-107..

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