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IJRPC 2013, 3(1) Chowdary et al ISSN: 22312781

20

INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY

Available online at www.ijrpc.com

PREPARATION AND EVALUATION OF STARCH - PEG

1500 CO-PROCESSED EXCIPIENT AS A NEW DIRECTLY

COMPRESSIBLE VEHICLE IN

TABLET FORMULATIONS

KPR. Chowdary*, P. Ravi Sankar and Syed Mahaboob Ali

Vikas Institute of Pharmaceutical Sciences, Rajahmundry, Andhra Pradesh, India.

INTRODUCTIONAn efficient platform for the manipulation ofexcipient functionality is provided by co-processing two or more existing excipients.Co-processing is based on the novel conceptof two or more excipients interacting at the sub

particle level, the objective of which is toprovide a synergy of functionalityimprovements as well as masking theundesirable properties of individualexcipients

1. The availability of a large number

Research Art i cle

ABSTRACT

An efficient platform for the manipulation of excipient functionality is provided by co-processing two or more existing excipients. Co-processing is based on the novel concept of

two or more excipients interacting at the sub particle level, the objective of which is toprovide a synergy of functionality improvements as well as masking the undesirableproperties of individual excipients. The objective of the present study is to prepare and

characterize starch - polyethylene glycol 1500 (Starch-PEG) co-processed excipient and toevaluate its application as directly compressible vehicle in tablet formulations. Starch-PEG

co-processed excipient was prepared by gelatinizing potato starch in the presence of PEG1500 and drying the resulting mass and was characterized by determining melting point,solubility, swelling index in water, pH, and micromeritic characters namely particle size,

bulk density, tapped density, angle of repose and compressibility index and evaluated for itsapplication as directly compressible vehicle in tablet formulations.

Starch-PEG co-processed excipient prepared was found to be granular, discrete and free

flowing. It is insoluble in water and aqueous fluids of pH 1.2, 4.5 and 7.4. It exhibited high

swelling (445%) in water. Starch-PEG co-processed excipient has excellent flow propertiesalone and as blends with selected drugs it exhibited excellent to good flow properties.

Tablets of (i) aceclofenac and (ii) ibuprofen prepared by direct compression methodemploying Starch-PEG co-processed excipient as DCV were of good quality with regard todrug content, hardness, friability and disintegration time. All the tablets formulatedemploying Starch-PEG co-processed excipient disintegrated rapidly within 15 seconds. Withboth the two drugs, the tablets prepared gave rapid dissolution of the contained drug.

Dissolution was complete with in 15-20 min in all the cases and fulfilled the official (I.P2010) dissolution rate test specification prescribed in each case. Thus Starch-PEG co-

processed excipient developed in this study was found to be a promising directlycompressible vehicle for the preparation of compressed tablets with fast dissolutioncharacteristics.

Keywords:Co- processed Excipient, , Directly compressible vehicle, Aceclofenac, Ibuprofen.

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of excipients for co-processing ensuresnumerous possibilities to produce tailor-madedesigner excipients to address specificfunctionality requirements. Co-processedexcipients are prepared by incorporating oneexcipient into the particle structure of anotherexcipient using processes such as co-drying.

Co-processing of excipients in thepharmaceutical industry can be dated back tothe late 1980s with the introduction of co-processed microcrystalline cellulose andcalcium carbonate

2, followed by Cellactose

(Meggle Corp.,Wasserburg, Germany) in1990, which is a co-processed combination ofcellulose and lactose. A similar principle wasapplied in developing silicified microcrystallinecellulose (Prosolve), which is the most widelyused co-processed excipient

3. The objective of

the present study is to prepare andcharacterize Starch Polyethyleneglycol(Starch-PEG) co-processed excipient and toevaluate its application as directlycompressible vehicle in tablet formulations.Starch-PEG co- processed excipient wasprepared by gelatinizing potato starch in thepresence of polyethylene glycol 1500 anddrying the resulting mass.

EXPERIMENTALMaterialsAceclofenac and ibuprofen were gift samplesfrom M/s Natco Laboratories Ltd., Hyderabad.Potato starch, PEG 1500, Crospovidone, talcand magnesium stearate were procured fromcommercial sources. All other materials usedwere of Pharmacopoeial grade.Afenak100 tablets of Ranbaxy LaboratoriesLtd., New Delhi ; Batch No. 9743788; Mfg.Date: April/2011; Exp. Date: March/2013 andBrufen 400 tablets of Abbott India Ltd., Goa;Batch No. 96809D7; Mfg. Date: 11/2010; Exp.Date: 10/2013 were procured from localmarket.

METHODSPreparation of Starch-PEG Co-processedExcipientPotato starch (9 g) was dispersed in 20 ml ofwater to form smooth slurry. PEG 1500 (1 g)was dissolved in purified water (40 ml) and thesolution was taken in a separate beaker and

heated to boiling. Starch slurry was added toboiling solution while stirring. Stirring whileheating was continued for 15 to 20 minutes toform a thick mass. The mass was dehydratedby the addition of acetone (20 ml) and mixing.The product formed was collected bydecantation and dried at 80

oC for 4 hours. The

dried product was grinded and sized to obtain -20+100 mesh sized particles.

Characterization of Starch-PEG Co-processed ExcipientStarch-PEG co-processed excipient preparedwas characterized by determining meltingpoint, solubility, swelling index in water, pH,and micromeritic characters namely particlesize, bulk density, tapped density, angle ofrepose and compressibility index.

SolubilitySolubility of Starch-PEGwas tested in water,aqueous buffers of pH 1.2, 4.5, and 7.4.

pHThe pH of a 1% w/v slurry was measured.

Melting po intMelting point was determined by using meltingpoint apparatus.

Swelling Index4

Starch-PEG (0.5 g) was added to 10 ml ofwater and petroleum ether taken in twodifferent graduated test tubes and mixed. Thedispersion in the tubes was allowed to standfor 24 hrs. The volumes of the sediment in thetubes were recorded. The swelling index of thematerial was calculated as follows.

S.I (%) = (Volume of sediment in water Volume of sedi ment in p etroleum ether)/(Volume of sediment in petroleum ether)

Particle sizeParticle size analysis was done by sievingusing standard sieves.

Bulk density5

Bulk density (g/cc) was determined by threetap method in graduated cylinder.

Angle of repose6Angle of repose was measured by fixed funnelmethod.

Compressibility index7

Compressibility index (CI) was determined bymeasuring the initial volume (V0) and finalvolume (V) after hundred tappings of a sampleof the product in a measuring cylinder.

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CI was calculated using equation,Compressibility index (CI) = [(V0-V)/V0] 100

Estimation of AceclofenacAn UV Spectrophotometric method based onthe measurement of absorbance at 275 nm inphosphate buffer of pH 6.8 was used for the

estimation of aceclofenac. The method wasvalidated for linearity, accuracy, precision andinterference. The method obeyed Beers law inthe concentration range of 1 10 g/ ml.When a standard drug solution was repeatedlyassayed (n=6), the relative error andcoefficient of variance were found to be 0.65 %and 1.45 % respectively. No interference bythe excipients used in the study was observed.

Estimation of IbuprofenAn UV Spectrophotometric method based onthe measurement of absorbance at 221 nm inphosphate buffer of pH 7.2 was used for theestimation of ibuprofen. The method wasvalidated for linearity, accuracy, precision andinterference. The method obeyed Beers law inthe concentration range of 1 10 g/ ml.When a standard drug solution was repeatedlyassayed (n=6), the relative error andcoefficient of variance were found to be 0.85 %and 1.15 % respectively. No interference bythe excipients used in the study was observed.

Preparation of Tablets by DirectCompression MethodTablets of (i) aceclofenac (50 mg) and (ii)ibuprofen (50 mg) were prepared by directcompression method as per the formulaegiven in the Table 2 employing Starch-PEGco- processed excipient as directlycompressible vehicle. All the materialsrequired as per the formula were blended in aclosed polyethylene bag. The blends werecompressed into tablets on a 10 station tabletpunching machine (Rimek) to a hardness of 6kg/cm

2using 9 mm flat punches.

Evaluation of TabletsAll the tablets prepared were evaluated forcontent of active ingredient, hardness,friability, disintegration time and dissolutionrate. Hardness of tablets was tested using

Monsanto hardness tester. Friability of thetablets was determined in a Roche Friabilator.Disintegration time was determined in a LabIndia tablet disintegration test machine (model:DT 1000) using water as test fluid.

Estimation of Drug Content in the TabletsFrom each batch of tablets prepared 10 tabletswere accurately weighed and powdered.Tablet powder equivalent to 50 mg of drug was

taken for assay into a 100 ml conical flask andextracted with 320 ml quantities of methanol.The methanolic extracts were filtered andcollected into a 100 ml volumetric flask and thevolume was then made upto 100 ml withmethanol. The solution was then suitablydiluted with phosphate buffer of pH 6.8 in the

case of aceclofenac; with phosphate buffer ofpH 7.2 in the case of ibuprofen. Theabsorbance of the solutions was measured at275 nm in the case of aceclofenac and at 221nm in the case of ibuprofen. Drug content ofthe tablets was calculated using the standardcalibration curve in each case.

Dissolution Rate StudyDissolution rate of the tablets prepared wasstudied employing USP 8 station DissolutionRate Test Apparatus (M/s Labindia Disso8000) with a paddle stirrer at 50 rpm.Phosphate buffer of pH 6.8 (900 ml) andphosphate buffer of pH 7.2 (900 ml) were usedas dissolution fluids for aceclofenac andibuprofen respectively. One tablet was used ineach test. A temperature 371

0C was

maintained throughout. Samples of dissolutionmedium (5 ml) were withdrawn through a filter(0.45 ) at different time intervals and assayedfor aceclofenac at 275 nm and for ibuprofen at221 nm. All the dissolution experiments wereconducted in triplicate (n=3).

RESULTS AND DISCUSSIONDirectly compressible vehicles can beprepared by various methods

[8 10]. Co-

processing is the one of the most widelyexplored and commercially utilized method forthe preparation of directly compressiblevehicles. Co-processing of excipients couldlead to the formation of excipients withsuperior properties compared to the simplephysical mixtures of their components. Theobjective of the present study is to prepare andcharacterize Starch-PEG co-processedexcipient and to evaluate its application asdirectly compressible vehicle in tabletformulations. Starch-PEG co-processedexcipient was prepared by gelatinizing potatostarch in the presence of PEG 1500 and dryingthe resulting mass. The prepared Starch-PEG

co-processed excipient was characterized bydetermining various physical and micromeriticproperties. The Starch-PEG co-processedexcipient prepared was granular, discrete andfree flowing. The physical and micromeriticproperties of Starch-PEG co-processedexcipient prepared are summarized in Table 1.The Starch-PEG co-processed excipientprepared was charred at 210

0C. It is insoluble

in water and aqueous fluids of pH 1.2, 4.5 and

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7.4. It exhibited high swelling in water and theswelling index was found to be 445 %. Theflow properties of the Starch-PEG co-processed excipient prepared weredetermined by measuring bulk density, angleof repose and compressibility index. Theresults given in Table 1 indicated that the

excipient prepared has excellent flowproperties. As the Starch-PEG co-processedexcipient possesses excellent flow propertiesand swelling character, it is considered as apromising directly compressible vehicle withgood disintegration characters for directcompression of tablets.

Table 1:Physical and Micro meriti c Properties of Starch-PEG 1500

Co-processed Excipient

S.No.Property/Test

Result

1. Melting point Charred at 2100c

2. SolubilityInsoluble in water and aqueous fluids of

acidic and alkaline pHs.

3. Swelling Index (%)High Swelling in Water.Swelling Index is 445%

4. pH (1% aqueous dispersion) 6.5

5. Particle size (m) 20/100 mesh

6. Bulk density (g/cc) 0.833

7. Tapped density (g/cc) 0.984

8. Angle of repose (o) 16.17

9. Compressibility index (%) 15.38

Blends of Starch-PEG co-processed excipientand selected drugs (aceclofenac andibuprofen) also exhibited excellent to good flowproperties. The estimated bulk density valuesof Starch-PEG co-processed excipient wouldalso contribute to its good flow.To evaluate the Starch-PEG co-processedexcipient as directly compressible vehicle(DCV), tablets (i) aceclofenac (50 mg) and (ii)ibuprofen (50 mg) were prepared by directcompression method employing Starch-PEG

co-processed excipient as DCV. The tabletswere prepared as per the formulae given Table2. All the tablets prepared were evaluated for

content of active ingredient, hardness,friability, and disintegration time anddissolution rate. The results are given in Table3. Hardness of the tablets was in the range 5.0- 5.5 Kg/sq.cm. Weight loss in the friability testwas in the range 0.87 1.12 %.The drugcontent of the tablets was within 100 3% ofthe labeled claim. All the tablets formulateddisintegrating rapidly within 15 seconds. Assuch all the tablets prepared employing theStarch-PEG co-processed excipient were of

good quality with regard to drug content,hardness, friability and disintegration time.

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Table 3: Physical Properties of Various TabletsPrepared By Direct Compression Method

Employing Starch-PEGCo-processed Excipient

FormulationHardness(kg/sq.cm)

Friability(% weight

loss)

Disintegrationtime(sec)

Drug content(mg/tablet)

Aceclofenac tablets 5.5 1.12 05-10 49.50

Ibuprofen tablets 5.0 0.87 10-15 49.25

Dissolution rate of formulated and commercialtablets was studied in each case. The resultsof the dissolution rate study are given in Table4. With both the two drugs, the tabletsformulated employing Starch-PEG co

processed excipient gave rapid dissolution ofthe contained drug. Dissolution was very rapidand complete with in 15-20 min in all the casesand fulfilled the official (I.P 2010) dissolution

rate test specification prescribed in each case.

Table 4:Dissolution Parameters of Tablets Prepared by Direct Compression Method

Employing Starch PEG Co-processed Excipient and Commercial Tablets

Formulation Dissoluti on Parameter Official Dissoluti on Rate

Specification

Dissolution

Observed

PD10(%) DE 20( %)

K1(min

-1)

Aceclofenac TabletsFormulated

88.05 78.90 0.187 NLT 70 % in 45 min in phosphatebuffer of pH 6.8 (I.P, 2010)

70 % in 5 min

Aceclofenac TabletsCommercial

81.36 69.96 0.055 NLT 70 % in 45 min in phosphatebuffer of pH 6.8 (I.P, 2010)

94 % in 45 min

Ibuprofen Tablets Formulated 81.79 74.30 0.118 NLT 50 % in 30 min in phosphatebuffer of pH 7.2 (I.P, 2010)

50 % in 4 min

Ibuprofen Tablets Commercial 98.5 82.83 0.420 NLT 50 % in 30 min in phosphate

buffer of pH 7.2 (I.P, 2010)

98.5% in 10 min

Dissolution data were analyzed as per zeroorder and first order kinetics. Drug dissolution

from the tablets followed first order kineticswith correlation coefficient (r) values > 0.985.The corresponding first order releasedissolution rates (K1) are calculated from theslope of the first order linear dissolution plots.The dissolution efficiency (DE20) values werecalculated as suggested by Khan

11. The

dissolution parameters are summarized inTable 4. Drug dissolution from the formulatedtablets was rapid and higher than that fromcommercial tablets in the case of aceclofenac.In the case of ibuprofen commercial tabletsgave relatively higher dissolution rates thanthe formulated tablets, but both gave 100 %

dissolution in 15 min.Thus Starch-PEG co-processed excipientcould be used as directly compressible vehiclein the formulation development of compressedtablets. Tablets of aceclofenac and ibuprofenformulated employing Starch-PEG co-processed excipient exhibited rapiddisintegration and dissolution ratecharacteristics and fulfilled the official (I.P)specifications with regard to various physicalproperties and dissolution characteristics.

CONCLUSIONStarch-PEG co-processed excipient prepared

was found to be granular, discrete and freeflowing. It is insoluble in water and aqueousfluids of pH 1.2, 4.5 and 7.4. It exhibited highswelling (445%) in water. Starch-PEG co-processed excipient has excellent flowproperties alone and as blends with selecteddrugs it exhibited excellent to good flowproperties. Tablets of (i) aceclofenac and (ii)ibuprofen prepared by direct compressionmethod employing Starch-PEG co-processedexcipient as DCV were of good quality withregard to drug content, hardness, friability anddisintegration time. All the tablets formulatedemploying Starch-PEG co-processed excipient

disintegrated rapidly within 15 seconds. Withboth the two drugs, the tablets prepared gaverapid dissolution of the contained drug.Dissolution was complete with in 15-20 min inall the cases and fulfilled the official (I.P 2010)dissolution rate test specification prescribed ineach case. Thus Starch-PEG co-processedexcipient developed in this study was found tobe a promising directly compressible vehiclefor the preparation of compressed tablets withfast dissolution characteristics.

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Tablet Excipients. ManufacturingChemist. 1993; 64(7):14-15.

2. Dev KM. Coprocessed MicrocrystallineCellulose and Calcium Carbonate andIts Preparation. US Patent No.4, 744,

987 to FMC Corporation(Philadelphia,PA) 1988.3. Bolhius GK and Chowhan ZT.

Materials for Direct Compaction.Pharmaceutical Powder CompactionTechnology. G.Alderborn andC.Nystron, Eds. Marcel Dekker Inc.,New York, NY, 1996:419-500.

4. Chowdary KPR and Sunil Kumar.Formulation development of selecteddrugs by direct compression method.IJPRD. 2011;3(6): 273-279

5. Martin A. Physical Pharmacy.Lippincott Williams &Wilkins Baltimore.2001:423-454.

6. Cooper J and Gunn C: Powder flowand compaction. Tutorial Pharmacy.CBS Publications, New Delhi,India,1986:211-233.

7. Aulton ME, Wells TI: Pharmaceutics;The Science of dosage form design.Churchill Livingstone, London,England, Edition 2,1988: 89-90.

8. Reimedes D. The Near Future ofTablet Excipients. Manuf Chem.1993; 64:14-15.

9. Shangraw RF, Wallace JW and BowesFM. Morphology and functionality inTablet Excipients for DirectCompression. Pharm Technol.1987;11:136-143.

10. Bolhuis GK and Chowhan ZT.Materials for Direct Compression.Pharmaceutical Powder CompactionTechnology. Marcel Dekker, USA.1996:7:419-499.

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