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Vol 4 - Cont. J. Pharm. Sci. 4.Pdfachor

Vol 4 - Cont. J. Pharm. Sci. 4.Pdfachor

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51
Continental J. Pharmaceutical Sciences 4: 51 - 55, 2010 ISSN: 2141 - 4149© Wilolud Journals, 2010 http://www.wiloludjournal.comTABLETING PROPERTIES OF ACID MODIFIED CASSAVA STARCH DEHYDRATED IN ALCOHOLAchor, M.
1
, Oyi, A.R
2
and Isah, A.B
2
 
1
Department of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, UsmanuDanfodiyo University, Sokoto, Nigeria,
2
Department of Pharmaceutics and Pharmaceutical Microbiology,Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria.ABSTRACTThe work was aimed to investigate the suitability of acid modified cassava starch (ACS) dehydrated inethanol for use as filler/binder in direct compression. ACS was obtained by acid hydrolysis usinghydrochloric acid at both 6.0 N and 8.0 N for 24 and 18 respectively. Powders retained on 150 µm sievewere used in tablet formulation. Tablets were made using metronidazole (200mg) in a ratio 1:1 usingthe direct compression method. The results obtained showed that there was a significant increase indissolution rate, crushing and tensile strength with reduced friability of ACS as compared to their nativeform. Generally, ACS showed increase dissolution rate profile and lower disintegration time ascompared to microcrystalline cellulose which showed a superior crushing and tensile strength.KEYWORDS: cassava starch, microcrystalline cellulose, acid hydrolysis, metronidazole, filler/binder.INTRODUCTIONCassava starch has many remarkable characteristics including high paste viscosity, high paste clarity and highfreeze-thaw stability, in particular, the native starch with high purity can be readily modified by physical,chemical and enzymatic process to many diversified products to improve the starch functionality andconsequently, encourage more industrial application. The simplest and most common starch modification is byacid hydrolysis which is widely used in food, paper, textile and pharmaceutical industries (Karntarat
et al
,2008). Acid modification changes the physicochemical properties of starch without destroying its granularstructure (Singh and Ali, 2000). It has been established that acid modified starch obtains improved properties asTableting excipient if the starch product obtained is first dehydrated by means of a water-miscible organicsolvent and the resulting starch product dried. The thus obtained starch powder has an increased specific surfacearea and, with respect to binding force and breaking strength, have improved properties as Tableting excipients(Buwalda and Willemina, 1997).Acid treatment can cause a breakdown of the polymeric structure in cassava powder to obtain a less elastic but amore plastic material which is amenable to direct compression (Florence and Roland, 2002). Recent advances informulation technologies have lead to a shift from traditional wet granulation to direct compressionmanufacturing process in the development of solid oral dosage forms due largely to process expedition, easyhandling, and time and cost savings (Nyström and Glazer, 1985). Tableting excipients are classified accordingto their functional properties such as binder, fillers, disintegrants, lubricants, flavors and coloring agents.Suitable starch products may also perform several functions, such as the combination of filler and binder (oftendesignated as filler/binder). In this study, acid modified cassava starch dehydrated in alcohol was evaluated forits suitability as a filler/binder in direct compression and subsequently compared with native cassava starch andmicrocrystalline cellulose (Avicel PH 101).MATERIALS AND METHODSMaterialsEthanol 96% (BDH Chemicals Ltd, Poole England), concentrated hydrochloric acid and sodium hydroxide(May and Baker Laboratory Chemical, Dagenham, England), metronidazole powder (Vingesh InternationalLimited, India), microcrystalline cellulose PH 101 (ATOZ Pharmaceuticals Limited, Ambaltur, India)Production of acid modified starchProduction of acid modified cassava starch was carried out as described by Buwalda and Willemina
 
(1997). 450grams of an aqueous suspension of starch (36% w/v wt starch) was poured into a stainless steel vessel. To thissuspension, 28ml, 6N and 8N HCL was added drop-wise with stirring. Subsequently the reaction was conductedfor 18 and 24 hours respectively at 50
o
C. After cooling, the modified starch product was separated from thereaction medium by filtration. On the filtrate, the separated starch product was washed 1:1 with water, then thestarch product was suspended again in 250ml water and brought to pH
 
6 with sodium hydroxide solution. The
 
52
Achor, M
et al
.,: Continental J. Pharmaceutical Sciences 4: 51 - 55, 2010starch product was separated by means of filtration with 750ml water. A sample of 100g of the wet starchproduct separated by filtration was suspended in 800ml ethanol and stirred for 30 minutes. Subsequently, thestarch product was separated by filtration and dried in Gallenkamp hot air oven (Philips Harris Ltd, England) at40
o
C. The dried starch was ground to fine powder and those fraction retained on 150
µ
m sieve were used forfurther studies.Preparation of tabletsAn Erweka tableting press (Erweka apparatebau GmbH, Germany) fitted with a 10.0 mm punch tip diameterwas used. Metronidazole tablets were formulated using the direct compression method at a ratio 1:1 withcassava starch, acid modified starches and microcrystalline cellulose (MCC PH101) as excipients with 0.5 %magnesium stearate as lubricant at a pressure setting of 9 metric tones using the following formulaTable 1: Formula for metronidazole tabletsFormulation Metronidazole(mg)Mag. St.(mg)CS(mg)ACS6(mg)ACS8(mg)MCC(mg)F1 200 2.0 200 _ _ _F2 200 2.0 _ 200 _ _F3 200 2.0 _ _ 200 _F4 200 2.0 _ _ _ 200KEYCS = cassava starch, ACS6 = acid modified cassava starch using 6N HCl for 24 hrs, ACS8 = acid modified vcassava starch using 8N HCl for 18 hrsEVALUATION OF TABLETSUniformity of weightTen tablets were weighed individually and collectively from each batch using Metler P163 balance (Zurich,Switzerland) and the mean weights computed. The percent coefficient of tablet weight variation (% CV) wascalculated according to the formula (Bolhuis, 1988)% CV = standard deviation/mean weight……………. (1).Density of tabletsDensities of tablets at corresponding pressure loads were used to evaluate compressibility. Tablet density wasobtained from the weight of compact and its volume as follows:Relative density (g/ml) = weight of tablet (g) / tablet volume (ml)………. (2)The volume of tablet was calculated from the relationship:Volume of tablet =
Π
r
2
t
ρ
……………….. (3)Where r = radius of tablet, andt = tablet thickness
ρ
= particle density of the granulesCrushing strengthThe Monsanto hardness tester was used to determine the crushing strength of five tablets from each batchtwenty-four hours to allow enough time for elastic recovery to occur after the tablets had been compressed.Tensile strengthThe radial tensile strength Ts of tablets was calculated from the equation:Ts = 2F / 
Π
dt ……………………….. (4)Where, F = load needed to break the tablet,d = diameter of tabletst = tablet thickness
 
53
Achor, M
et al
.,: Continental J. Pharmaceutical Sciences 4: 51 - 55, 2010Friability testTen tablets were dusted, weighed together and subjected to abrasion test in the Erweka TA3R friabilator(Erweka apparatebau GmbH, Germany) operated at 25 rpm for 4 minutes. The tablets were then dusted properlyand weighed again collectively. The difference in weight was then determined and expressed as percentagefriability value.Disintegration time studiesThe disintegration time of tablets was determined with Erweka disintegration apparatus (ZT3), (Erwekaapparatebau GmbH, Germany) using the BP (2004) method. Water thermostatically maintained at 37
o
 
±
0.5
o
Cwas the medium. The time taken for all of the six tablets, one placed in each of the six tubes of the apparatus todisintegrate and pass through the mesh was recorded using a stop clock.Dissolution testsErweka disintegration apparatus ZT3 (Erweka apparatebau GmbH, Germany) was utilized using the basketmethod. One tablet was placed in the dry basket and lowered into the dissolution medium (0.1 N HCl) half waybefore the rotation began at a speed of 100 rpm. 10 ml of the sample was withdrawn from half way between thesurface of the dissolution medium and the top of the rotating basket at 10 minutes interval for one hour. Afterevery withdrawal, 10 ml of the medium was replaced. A one in ten dilution with the dissolution media was madebefore the absorbance of the sample was taken at 277 nm with Genesys 20 spectrophotometer (Madison,Wisconsin, USA).Statistical analysisStatistical analysis was done to compare the crushing and tensile strength of the formulation between MCCPH101, cassava starch and acid modified starches using the t-test. At 95% confidence interval,
ρ
value lower orequal to 0.05 was considered the limit of significance.RESULTS AND DISCUSSIONSWight uniformity of metronidazole tablets can be attributed to the flow characteristics of the excipients withMCC PH101 known to have a poor flow properties as compared to acid modified cassava starch (Achor
et al
,2010). The density of the tablets also reflects the densities of the excipients as reported by Achor
et al
(2010).The results of friability test for metronidazole tablets as shown in Table 2 shows that MCC PH 101 had betterfriability value (F
4
) as compared to cassava starch and its modified products (F
1
,F
2
and F
3
). This can beattributed to the crushing strength of the tablets. Disintegration of tablets can be considered as the result of twoprocesses; water uptake and the separation of the particles due to elastic expansion of the compressed particlesand annihilation of the interparticulate hydrogen bonds followed by penetration of water between the particles(Michael, 2006). The more compact a tablet is, the less the porosity and hence less penetration of water into thetablet and as a result, longer disintegration time. All starch types for metronidazole tablets passed the BP (2004)specification for disintegration of uncoated tablets (within 15 min) except MCC PH 101. This can be attributedto the stronger bonds coupled with the impairment of swelling ability by better compressibility of MCC PH 101.This retards water penetration and cause tablet rupture less readily.Table 2: Properties of metronidazole tabletsParameters F1 F2 F3 F4Wt. uniformity(%coefficient)1.48 1.89 1.96 2.80Density (g/cm3) 1.19 (1.12) 1.17 (0.35) 1.20 (0.84) 0.96 (1.20)Disintegration (min.) 8.00 (0.08) 11.00 (0.12) 16.00 (0.10) 40.00 (0.45)Friability (%) 3.61 (0.05) 2.98 (0.03) 2.21 (0.02) 2.12 (0.02)*value is mean and standard deviation is in parenthesis, number of replicate = 3KEY: F1, F2, F3 and F4 represents metronidazole tablets formulated using CS, ACS6, ACS8 and MCC PH101respectively as excipients.Metronidazole tablets formulated using acid modified cassava starch showed tablets with higher crushing andtensile strengths as compared to its native from (Fig. 1) The crushing strength of a tablet, like its thickness, is afunction of the die fill and compression force. In an ideal situation, at a constant die fill, the crushing strengthvalues increase and thickness decreases as additional compression force is applied. Metronidazole tablets

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