http://informahealthcare.com/phb ISSN 1388-0209 print/ISSN 1744-5116 online Editor-in-Chief: John M. Pezzuto Pharm Biol, 2014; 52(8): 935–943 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/13880209.2013.873812
ORIGINAL ARTICLE
Comparative binding and disintegrating property of Echinochloa colona starch (difra starch) against maize, sorghum, and cassava starch Daud Baraka Abdallah1, Naseem Ahmad Charoo2, and Abubakr Suliman Elgorashi1 Department of Pharmaceutics, Faculty of Pharmacy, Al Ribat University, Khartoum, Sudan and 2Innovation and Development, Xepa-Soul Pattinson (M) Sdn Bhd, Melaka, Malaysia
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Abstract
Keywords
Context: Starch obtained from different botanical sources exhibit different characteristics due to variation in amylase–amylopectin ratio, which results in different binder substrate interactions. Objective: The present study characterized Echinochloa colona (L.) Link (Poaceae) starch and evaluated its compressional characteristics for use as tablet excipient against commonly used maize, sorghum, and cassava starch. Materials and methods: Three experimental design studies were performed to determine the effects of the maize starch and povidone on physical properties of paracetamol (250 mg) tablets. The effect of superdisintegrants sodium starch glycolate and croscarmellose sodium on the optimized composition obtained in the preceding experiments was evaluated in two factorial experimental studies. The maize starch in the optimum formulations was replaced with difra, sorghum, and cassava starch, and tablets prepared from these starches were compared for their compressional characteristics, lubrication sensitivity, moisture uptake, and drug release. Results: Tablets prepared from maize starch and povidone (30:9, w/w) blend which was previously mixed for 8 min disintegrated (DT) in 10 min. Superdisintegrants decreased DT of tablets significantly (p50.05) to 2.2 min. The Hausner ratios of co-processed mixtures containing sorghum, maize, and difra starch were 1.19, 1.21, and 1.26, respectively, with equilibrium moisture content of 8–9%. The DT of sorghum and difra starch formulations which related directly to their higher hydration capacity (difra4sorghum4maize starch) and swelling property was 1.5 min and 2.5 min, respectively, with a friability of 0.32%. The effect of lubrication on the DT and friability of tablets containing maize and difra starch was significant (p50.05). However, more than 90% drug was released in vitro dissolution studies. Conclusion: Difra starch can replace maize and sorghum starch as tablet excipient.
Disintegration time, hydration capacity, lubrication sensitivity, swelling capacity, tablet compression, tensile strength, wet granulation
Introduction Active pharmaceutical ingredients should have optimum compressibility, flow properties, stability, and dissolution characteristics to be manufacturable and produce the intended pharmacological action. However, they do not possess these attributes per se and hence excipients are incorporated in the solid dosage formulations. An excipient when used alone cannot impart all these characteristics; therefore, multiple excipients are included in a formulation. Co-processed mixtures are now available commercially as mixtures of excipients that provide performance advantage which are otherwise not achieved by admixing the same composition (Block et al., 2009). For example, co-processed excipient mixture of microcrystalline cellulose, mannitol, and hydroxypropyl cellulose prepared by high shear mixing exhibited good or better pharmaceutical filler characteristics
Correspondence: Dr. Naseem Ahmad Charoo, Xepa-Soul Pattinson Sdn Bhd, 1-5 Cheng Industrial Estate, 75250 Melaka, Malaysia. Tel: +60 1 42361872. E-mail: [email protected]
History Received 18 June 2013 Revised 1 November 2013 Accepted 23 November 2013 Published online 19 February 2014
compared to lactose and calcium phosphate formulations (Jian-Xin et al., 2008; Sherwood et al., 1996; Westerhuis et al., 1996). Starch is a multipurpose excipient identified as one of the top 10 excipients in a joint conference on excipients (Shangraw, 1992). Corn starch is the most commonly used type of starch used in solid dosage formulations (Shangraw, 1992). Native starches obtained from breadfruit and cocoyam have also shown promise for their use in solid dosage forms (Adebayo & Itiola, 1998a,b). The binding and disintegrant properties of sorghum and plantain starches have been investigated (Adebayo & Itiola, 1998a,b; Kottke & Rhodes, 1991; Rowe, 1989). Corn starch is mainly used in the form of a paste in wet granulation process and its utility as a binding agent for hydrophobic drugs has been proven (Rowe, 1989). Adebayo and Itiola (1998b) reported superior hydration and moisture sorption capacities of breadfruit and cocoyam starches as compared to corn starch. These properties impart suitable characteristics to these starches making them useful mucilaginous binding agents. Various brands of corn starch were found to have insignificant effect on dissolution profiles of drugs (Kottke & Rhodes, 1991).
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However, starch from different botanical sources produced pastes with different characteristics due to variation in amylase–amylopectin ratio, which resulted in different binder substrate interactions (Alais & Linden, 1999). Moisture content of starch depends on its storage condition. Due to its effect on viscoelasticity, the compressibility of starch is determined by this residual moisture content (Rees & Tsardaka, 1994). At about 10% of moisture content, the tablets exhibit maximal binding characteristics (Bos et al., 1987). Even though native starches possess good compression properties but poor flow precludes their use as dry binders in direct compression formulations (Jivraj et al., 2000). Further, due to their plastic deformation, starches exhibit high lubricant sensitivity (Jarosz & Parrot, 1984). Povidone is a polymeric binder used mainly in the wet granulation process. On hydration, it produces viscous and tacky solution which binds the granules together. It is also added as a powder to the blend and then activated by solvent in situ. However, several technical problems such as over granulation problems, tablet hardening, and decrease in dissolution are associated with its use in granulation (Anonymous, 2009; Moore & Flanner, 1996). Povidone and starch in a dosage form may provide advantages of both good compaction and disintegration characteristics. The climate and fertile soil of Sudan are favorable for growing different types of starch such as wheat, corn, sorghum, and potato. Sudan rates among the leading producers of sorghum starch in Africa with annual production of 4 470 000 MT (21% of total production in Africa). Echinochloa colona (L.) Link (Poaceae) (syn. Panicum colonum) difra grass grows annually in small tufts to approximately 60 cm height mainly in the Kordofan and Darfur region (Dalziel, 1948). The seeds are harvested in the month of August, September, and October and ground to prepare flour for consumption as Asida and Kisra. The present study develops a formulation composition with locally grown difra starch having sufficient interparticle cohesive strength needed for commercial production of tablets with the desired attributes. The comparative binding, disintegrant efficacy, and lubricant sensitivity of difra starch versus other commonly used starch excipients in a tablet formulation containing povidone and prepared by wet granulation technique was also studied. Suitability of difra starch for use as a table excipient can obviate the need for local pharmaceutical and food industry to import expensive starch. In addition, it can open new avenues for exporting starch to the wider African region.
Materials and methods A gift sample of paracetamol, polyvinyl pyrrolidone (PVP), maize starch, magnesium stearate, croscarmellose sodium, and sodium starch glycolate was received from Blue Nile Pharmaceutical Company, Khartoum, Sudan. Native starches were purchased from local market and extraction process was carried out by the authors in the laboratory. All other chemicals and solvents were of analytical grade. JMPÕ (SAS Campus Drive, Building T, Cary, NC) software was used to perform ANOVA (results with p values, 0.05 were considered significant) and generate graphs.
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Table 1. Experimental design for preliminary experiments with different binders. Factors Run
F1 (wet massing time)
F2 (povidone)
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12
þ1 (12) 1 (4) þ1 (12) 0 (8) þ1 (12) 0 (8) 1 (4) 1 (4) þ1 (12) 0 (8) 1 (4) 0 (8)
þ1 (15) þ1 (15) þ1 (15) 1 (9) 1 (9) þ1 (15) 1 (9) þ1 (15) 1 (9) 1 (9) 1 (9) þ1 (15)
F3 (starch) þ1 þ1 1 þ1 1 1 þ1 1 þ1 1 1 þ1
Tablet weight (mg)
(30) (30) (15) (30) (15) (15) (30) (15) (30) (15) (15) (30)
298 298 283 292 277 283 292 283 292 277 277 298
The figures in brackets show the actual quantities used.
Preliminary experiments with different binders Three factorial experimental design (2 2 3) was adopted to evaluate the effect of corn starch and PVP binders at two levels each and the wet massing time at three levels as shown in Table 1. The batch size in all the runs was 157 g. The specified amount of paracetamol and PVP was sifted through BSS (British Standard Sieve Series; Filterwel Test Sieves, Mumbai, India) # 30 and mixed in a planetary mixer (Cnum5ST, Bosch- Ljubljana, Solvenia) for 10 min at 47 rpm. Starch slurry was prepared by dispersing it in 15 mL of cold water. Approximately 40 mL hot water heated at 90–100 C for 30 min was added to the starch slurry while continuously stirring it to obtain a smooth starch paste. The cooled starch paste was added to the mixture of paracetamol (250 mg/tablet) and PVP. The starch paste vessel was rinsed further with 3 mL water and added to the mixture. The granulation process was performed at 47 rpm for the specified time with a stopover at one-third and two-third of time to scrape the blades and sides using spatula. The wet mass was then screened through BSS# 12 sieve and dried at 40–50 C for 1 h or more till loss on drying (LOD) (105 C for 10 min) was less than 5% w/w. The dried granules were passed through BSS # 20. The granules were lubricated with 1% w/w magnesium stearate for 2 min and then compressed into tablets using a single punch tableting machine (Erweka Type EP-1, Heusenstamm, Germany) with a punch diameter of 9 mm and a compression force of 4–8 KP. Similarly the effect of superdisintegrants sodium starch glycolate (7.5 and 15.0 mg/tablet) and croscarmellose sodium (7.5 and 15.0 mg/tablet) on the optimized tablet composition was evaluated in a two factorial experimental study using the same process as provided above except disintegrant was added in equal proportions in intra and extra granular portions. Compressional characteristics of tablets prepared with native starches grown in Sudan in comparison with tablets prepared with commonly used maize starch The effect of difra starch, grown in Sudan, on binding and disintegration properties of paracetamol tablets was evaluated against the commonly used maize and sorghum starch.
Comparative binding of difra
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Starch type was the only variable in tablet compositions, which were prepared with the same procedure as outlined above. The starches were extracted using the following procedures. (a) Extraction of starch from pearl millet (Ashana variet; Pennisetum glaucum (L.)R. Br., (Poaceae) and Sorghum bicolor (L.) Moench (Poaceae) The starch was extracted from the two grains according to a combination of methods (Abdalla et al., 2009; Beleia et al., 1980). To inhibit microbial growth, millet grains were soaked at 4 C for 24 h in distilled water containing 0.01% sodium azide. Grains were then washed several times with distilled water, wet-milled in a blender for 3 min and screened through 200 mesh sieve. The process of wet-milling was repeated until no more starch could be separated. The starch suspension was centrifuged (Labspin-TC450C, Eltek, Mumbai, India) at 626 g for 20 min and the upper nonstarch layer was removed with spatula and discarded. The starch (lower layer) was suspended in water, centrifuged, and the tailings were scraped with spatula. The last step was repeated until a white prime starch (free of tailings) was obtained which was air-dried. The same procedure was followed for sorghum bicolor. (b) Extraction of starch from E. colona (difra) The method described in section (a) was used with slight modifications. The grains were first dehulled using a wooden mortar and pestle and washed several times with distilled water. The non-dehulled grains and any other foreign materials were isolated manually. The pure grains were soaked in distilled water containing 0.01% of sodium azide at 4 C for 24 h. Grains were then washed and treated by the same procedure used for obtaining starch from pearl millet and sorghum bicolor (c) Extraction of starch from cassava tubers The starch was extracted from root tubers of cassava [Manihot esculenta Crantz, (Euphorbiaceae)] according to the method of Yamini et al. (2011). Fresh cassava tubers were peeled, washed, and chopped into small pieces. The tubers were milled to a pulp using mixer and more distilled water was added to give dilute slurry which was sieved using 200 mesh sieve. This process was repeated until no more starch was extracted. The starch was precipitated out, washed many times, and the prime white starch obtained was air-dried. The starch was then passed through a 200 mesh sieve and evaluated for swelling and hydration capacity. Swelling capacity The swelling capacity of the three types of starches was determined by using the method of Olayemi et al. (2008) by running experiments in triplicate. Each starch (5 g) was accurately weighed and the tapped volume occupied by this amount (Vi) was noted. The powder was then dispersed in 85 mL of distilled water and the volume was made to 100 mL with the distilled water. After 24 h, the volume occupied by the sediment (Vf) was estimated for calculating swelling capacity. Swelling capacity ¼ Vf =Vi
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Hydration capacity One gram of each of starch powder (Y) was placed in a centrifuge tube and 10 mL of distilled water were added (Olayemi et al., 2008). The tube was shaken intermittently for 2 h and allowed to stand for 30 min before centrifugation for 10 min at 1409g in a bench centrifuge. The supernatant was decanted and the weight (X) of the powder after centrifugation was determined. Measurements were done in triplicate. The hydration capacity was calculated as Hydration capacity ¼ X=Y Compression properties and moisture uptake comparison of co-processed mixture prepared from different types of starch The co-processed mixtures of the optimized formulations were prepared by direct mixing and wet granulation techniques. Mixtures prepared by dry granulation were found to have insufficient compressibility. A direct mixture of starch (30 mg/tablet) and povidone (9 mg/tablet) was prepared by sifting them through BSS# 20 followed by mixing for 5 min at 12 rpm in octagonal blender (Erweka, Heusenstamm, Germany). Co-processed mixture by wet granulation was prepared by sifting starch and povidone through BSS#20. The mixture was granulated with water. The wet mass was passed through BSS# 12 and dried at 50–60 C in an oven. The dried granules were sifted through BSS #20 to break any lumps. Moisture uptake, particle size distribution, and angle of repose of mixtures were recorded. Moisture uptake This was determined by spreading 5 g sample uniformly in a Petri-plate. The samples were stored at room temperature and in a desiccator maintained at 25 C and 75% RH by saturated sodium chloride salt solution. The samples were withdrawn at predefined time intervals and conditioned at room temperature before weight gain was recorded. Comparative study of tablets containing difra starch with tablets prepared from corn starch, sorghum starch and cassava starch Maize starch in the optimized formulation was replaced with different types of starch and the physical characteristics of granules prepared by wet granulation using the same procedure as mentioned above were recorded. Tablets were evaluated for hardness (Caleva, model THT 500, Sturminster Newton, UK), compressibility index (Schwartz et al., 1975; Stanley-Wood & Shubair, 1979), weight uniformity reported as % CV (Mettler, AE 260, Mettler-Toledo, Switzerland), disintegration time (Erweka ZT 321, Heusenstamm, Germany), friability (Erweka, TA 120, Heusenstamm, Germany), and dissolution (Erweka type DT 800 low head, Heusenstamm, Germany) (USP, 2013). Fourier transform infrared spectroscopy: About 1–2 mg of test sample was triturated with 100 mg of potassium bromide and placed in the sample cup and made uniform with sample prodding bar. Infrared absorption spectrum in the range 400– 4000 cm1 was recorded at room temperature in Shimadzu FTIR instrument at a resolution of 1 cm1.
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Lubrication sensitivity Effect of lubricant (0.5%, 1.0%) and lubrication time (5 min; 10 min) on tablets prepared from different types of starches (maize, difra, and sorghum) was evaluated in a three factorial (3 2 2) experimental design study. Tablets were prepared by the same procedure as provided above and evaluated for DT, dissolution, and friability %.
Results and discussion
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Preliminary experiments with different binders The binding properties of polyvinyl pyrrolidone and binding/ disintegrant properties of corn starch were tested in the wet granulation process. The effect of wet massing time was also evaluated. The physical characteristics of the formulations are presented in Figure 1. At 12 min wet massing time, increase in povidone concentration led to increase in DT from 13 min (formulation 9) to more than 30 min (formulation 1). The % CV of formulations 2, 3, and 4 was 1.4, 0.52, and 0.71, respectively. The povidone was found to be better binder than starch. This was further confirmed by low friability % values of 0.97, 0.79, and 0.42, respectively, for these formulations. The low % CV and % friability are indicators of uniformity, good flow, and compressibility properties of the formulation mixtures. These parameters are essential for scale-up consideration.
DT decreased to 10 min and friability to 0.42% when starch (30 mg) and povidone (9 mg) in their highest and lowest concentrations, respectively, were mixed for 8 min in formulation 4. Starch at higher concentration showed better disintegrating properties as is evident from the contour plot (Figure 1). A further increase in mixing time had a negative effect on DT as was noticed in formulation 9, which disintegrated in 13 min. This deleterious effect on DT was more evident in formulations containing starch and povidone at their maximum levels. The DT increased from 25 min in formulation 2 to 36 min in formulation 1 with increased mixing time. At the same time, mixing time of 4 min was insufficient for effecting suitable binding as is evident from high % CV values of 2.41, 5.10, and 4.60 for formulations 7, 8, and 11, respectively. Granules of optimum strength can be produced only when the binder solution is uniformly distributed and spread on the powder blend. However, at higher mixing time, the granules tend to become harder and may fail in dissolution or pose challenges in compression. The effects of superdisintegrants sodium starch glycolate and croscarmellose sodium on compressional properties were evaluated in an experimental designed study. Sodium starch glycolate and croscarmellose sodium are modified starch and cellulose molecules formed by cross-linking of the organic chains. They swell on coming in contact with water and exert pressure in radial direction leading to disintegration of tablets. Other mechanisms involved in their disintegrant activity are
Figure 1. Physical characteristics of preliminary formulations.
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Figure 2. Response surface plots depicting effect of disintegrants on DT and % friability.
wicking, deformation recovery, and particle repulsion (Abu-lazza et al., 2004; Zhao & Augsburger, 2005). The DT was significantly reduced from 10 min to 2.2 min in formulations containing lower concentration of disintegrants. However, further increase in their concentrations did not affect DT significantly (p40.05, ANOVA followed by Tukey’s test). The response surface plots (Figure 2) elucidate the relationship between variables. Both the disintegrants had negative effects on percentage friability as they reduced the bonding force between the particles in the granules. The % friability increased to 1.5% from 0.42% when they were used at their highest levels. The first-order model equation obtained for the DT and friability % was DT ¼ 3:1 þ 0:9 ðcroscarmellose sodium concentrationÞ Friability% ¼ 1:175 þ 0:275 ðsodium starch glycolateÞ þ 0:225 ðcroscarmellose sodium concentrationÞ
The coefficient of the interaction was zero and the effect of sodium starch glycolate on DT was not noticed. The results obtained are similar to those reported by Quadir and Kolter (2006) who noted higher swelling pressure exerted by croscarmellose sodium as compared to sodium starch glycolate. Compression properties and moisture uptake comparison The Hausner ratios of co-processed mixtures prepared by direct mixing were 1.45, 1.81, and 1.38, respectively, for maize starch, difra starch, and sorghum starch. Similarly the Hausner ratios of mixtures prepared by the wet mixing process were 1.21, 1.26, and 1.19, respectively, for maize, difra, and sorghum starches. Hausner ratio and compressibility values below 1.25 and 25% indicated good flow characteristics imparted by the wet granulation process. The moisture uptake
capability of all the mixtures obtained by wet granulation under high humidity conditions was almost similar. The equilibrium moisture uptake of 8–9% was observed after 4 d of storage at 75% RH. The LOD values determined at 105 C for 20 min were 8.9, 7.8, and 8.7%, respectively, for co-processed mixtures obtained with sorghum, difra, and maize starch. Comparative study of tablets containing difra starch with tablets prepared from corn, sorghum, and cassava starch The effect of different starch grades on the compressional characteristics of paracetamol tablets was evaluated by replacing maize starch in the optimized formulation obtained above with its other grades. The bulk and tap density of all the starches were in the range of 0.47–0.51 and 0.63–0.68, respectively. Similarly, Hausner ratio and angle of repose values were 1.3–1.45 and 33–35, respectively. Hausner ratio indicated moderate flow characteristics of starches due to low inter-particulate friction (Sherwood et al., 1996). The results were confirmed by the Carr index values of 23–30; also, all the starches showed the similar particle size distribution (Figure 3). The tablet characteristics are shown in Figure 4. Regardless of the starch type, the friability in all the formulations was 0.32%. The DT of sorghum and difra starch formulations was 1.5 min and 2.5 min, respectively. The hydration capacity of sorghum, difra, and maize starch was 1.81, 1.90, and 1.46, respectively. Similarly their swelling capacity was 1.21, 1.28, and 1.07, respectively. The hydration capacity of an excipient determines water penetration which precedes tablet disintegration (Caramella, 1984). Swelling capacity of starch depends on its amylopectin content and the two are inversely proportional (Tester et al., 2004). The higher hydration and swelling capacity of sorghum and difra starch
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impart them good disintegration properties. Absorption of large quantities of water due to the higher swelling capacity of sorghum and difra starch would generate a higher swelling force leading to faster disintegration of the tablet (GuyotHermann, 1992). Our results are in agreement with the findings of Garr and Bangudu (1991) who reported that sorghum starch was as an effective binder as maize starch and exhibited about twice the disintegrant activity as compared to maize starch. In another study, sorghum starch
was found to have better binding and disintegrant properties than maize starch and better binding properties than acacia (Deshpande & Panya, 1987). Cassava starch has been found to possess superior binding property as compared to cocoyam starch and maize starch due to higher gel strength of its mucilages (Uhumwangho et al., 2006). However, the DT of tablets tends to increase which explains the high DT (7 min) of tablets prepared from cassava starch (Figure 5). The FTIR spectra of the final dosage forms were almost a superposition of the spectra of starch, PVP, and paracetamol (figure not shown). The presence of the same bands suggests the absence of any chemical interaction.
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Lubrication sensitivity
Figure 3. Particle size distribution of blends prepared by suing starch from different sources.
Starch undergoes plastic deformation and may be sensitive to high lubricant concentration. As shown in Figure 4, the effect of magnesium stearate concentration and lubrication time on DT and the % friability of sorghum starch was insignificant (p40.05). With the increase in magnesium stearate concentration and mixing time from 0.5% and 5 min to 1% and 10 min, respectively, the DT of formulations containing difra starch increased from 3.55 to 7 min, respectively (p50.05). Friability % values also increased to 1.6% from 1% indicating the synergistic effect of lubrication time and magnesium stearate concentration. However, no effect on dissolution was observed as 490% drug release was observed after 10 min (Figure 6). The effects of boundary lubricants like magnesium stearate are more pronounced in excipients exhibiting plastic
Figure 4. Effect of lubrication on tablet DT and % friability.
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Figure 5. Effect of different types of starch on DT and weight variation.
deformation (Hussain, 1990). The higher plasticity of difra starch may contribute in its sensitivity to magnesium stearate concentration and lubrication time. As deduced from Figures 4 and 6, the lubricants can be used at lower concentrations and lubrication time should be maintained below 5 min, similar results were obtained with maize starch formulations. The DT almost doubled to 10.24 min with an increase in magnesium stearate concentration and lubrication time; however, more than 88% drug was released after 10 min. The tensile strength of tablets increased with the increase in compression force. The tensile strength of tablets prepared from maize, difra, and sorghum starch containing 0.5% lubricant, lubricated for 5 min, and compressed at 3 KN was 0.91, 0.92, and 0.74, respectively (Figure 7). Tablets of higher
strength were obtained from blends containing difra and maize starch.
Conclusion Difra starch has many suitable attributes as tablet excipient and can replace conventional maize and other types of starch excipients. It exhibited good compressibility and fast dissolution behavior. The powder properties were similar to maize and sorghum starch. Moisture uptake capabilities at higher humidity conditions were also similar. The tabletting behavior of starches was also comparable. Tablets prepared from sorghum and difra starch demonstrated lower DT values. The advantage of fast disintegration will translate into fast drug
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Figure 6. Effect of lubrication on drug release. Key: formulations: 1 ¼ 1 þ þ; 2 ¼ 1 þ; 3 ¼ 1 þ ; 4 ¼ 1 ; 5 ¼ 2 þ þ; 6 ¼ 2 þ; 7 ¼ 2 þ ; 8 ¼ 2 ; 9 ¼ 3 þ þ; 10 ¼ 3 þ ; 11 ¼ 3 þ ; 12 ¼ 3 ; ‘‘1’’, sorghum starch; ‘‘2’’, difra starch; ‘‘3’’, maize starch; ‘‘þ’’, high lubricant concentration; ‘‘’’, low lubricant concentration; ‘‘þ’’, high lubrication time; ‘‘’’, low lubrication time.
Figure 7. Effect of lubrication on tensile strength of tablets prepared from different starch types.
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dissolution as seen in drug release studies. No interaction with drug or excipients was observed. Tensile strength of tablets prepared with difra starch was better than sorghum starch and comparable to maize starch tablets. The results of these studies have established that difra starch has excellent binding and disintegrant properties.
Declaration of interest The authors report no declaration of interest.
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Jarosz PJ, Parrot EL. (1984). Effect of lubricants on tensile strength of tablets. Drug Dev Ind Pharm 10:259–73. Jian-Xin LI, Brian C, Thomas R. (2008). Co-processed microcrystalline cellulose and sugar alcohol as an excipient for tablet formulations. Applicant: FMC Corp. (US), European Patent Office, Patent No. US20080131505. Jivraj M, Martini LG, Thomson MC. (2000). An overview of the different excipients useful for the direct compression of tablets. Pharm Sci Technol Today 3:58–63. Kottke MK, Rhodes CT. (1991). Limitations of presently available in vitro release data for the prediction of in vivo performance. Drug Dev Ind Pharm 17:1157–76. Moore JW, Flanner HH. (1996). Mathematical comparison of dissolution profile. Pharm Tech 20:64–74. Olayemi OJ, Oyi AR, Allagh TS. (2008). Comparative evaluation of maize, rice and wheat starch powders as pharmaceutical excipients. Nig J Pharm Sci 7:154–61. Quadir A, Kolter K. (2006). A comparative study of current superdisintegrants. Pharm Tech 30:PS38–42. Rees JE, Tsardaka KD. (1994). Some effects of moisture on the viscoelastic behaviour of modified starch during powder compaction. Eur J Pharm Biopharm 40:193–7. Rowe RC. (1989). Surface free energy and polarity effects in the granulation of a model system. Int J Pharm 53:75–8. Schwartz JB, Martin ET, Deliner EJ. (1975). Intragranular starch: Comparison of starch U.S.P and modified corn starch. J Pharm Sci 64: 328–32. Shangraw RF. (1992). International Harmonization of Compendia Standards for pharmaceutical excipients. In: Crommelin DJA, Midha K, eds. Topics in Pharmaceutical Science. Germany, Stuttgart: Medpharm Scientific Publishers, 205–23. Sherwood BE, Hunter EA, Staniforth JH. (1996). Pharmaceutical excipient having improved compressibility. Applicant: Edward H Mendell Co. Inc. (US), United States Patent Office, Patent No. 5,585,115. Stanley-Wood NG, Shubair MS. (1979). The influence of binder concentration on the bond formation of pharmaceutical granules. J Pharm Pharmacol 31:429–33. Tester RF, Karkalas J, Qi X. (2004). Starch composition, fine structure and architecture (review). J Cereal Sci 39:151–65. USP 36-NF 31. 2013. The United States Pharmacopoeia – The National Formulary. Rockville (MD): The United States Pharmacopoeial Convention, Inc. Uhumwangho MU, Okor RS, Eichie FE, Abbah CM. (2006). Influence of some starch binders on the brittle fracture tendency of paracetamol tablets. Afr J Biotech 5:1950–3. Westerhuis JA, De Haan P, Zwinkels J, et al. (1996). Optimisation of the composition and production of mannitol/microcrystalline cellulose tablets. Int J Pharm 143:151–62. Yamini K, Chalapathi V, Reddy NL, et al. (2011). Formulation of diclofenac sodium tablets using tapioca starch powder – A promising binder. J Appl Pharm Sci 1:125–7. Zhao N, Augsburger LL. (2005). The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide form directly compressed tablets. AAPS Pharm Sci Tech 6:E120–6.
ORIGINAL ARTICLE
Comparative binding and disintegrating property of Echinochloa colona starch (difra starch) against maize, sorghum, and cassava starch Daud Baraka Abdallah1, Naseem Ahmad Charoo2, and Abubakr Suliman Elgorashi1 Department of Pharmaceutics, Faculty of Pharmacy, Al Ribat University, Khartoum, Sudan and 2Innovation and Development, Xepa-Soul Pattinson (M) Sdn Bhd, Melaka, Malaysia
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Abstract
Keywords
Context: Starch obtained from different botanical sources exhibit different characteristics due to variation in amylase–amylopectin ratio, which results in different binder substrate interactions. Objective: The present study characterized Echinochloa colona (L.) Link (Poaceae) starch and evaluated its compressional characteristics for use as tablet excipient against commonly used maize, sorghum, and cassava starch. Materials and methods: Three experimental design studies were performed to determine the effects of the maize starch and povidone on physical properties of paracetamol (250 mg) tablets. The effect of superdisintegrants sodium starch glycolate and croscarmellose sodium on the optimized composition obtained in the preceding experiments was evaluated in two factorial experimental studies. The maize starch in the optimum formulations was replaced with difra, sorghum, and cassava starch, and tablets prepared from these starches were compared for their compressional characteristics, lubrication sensitivity, moisture uptake, and drug release. Results: Tablets prepared from maize starch and povidone (30:9, w/w) blend which was previously mixed for 8 min disintegrated (DT) in 10 min. Superdisintegrants decreased DT of tablets significantly (p50.05) to 2.2 min. The Hausner ratios of co-processed mixtures containing sorghum, maize, and difra starch were 1.19, 1.21, and 1.26, respectively, with equilibrium moisture content of 8–9%. The DT of sorghum and difra starch formulations which related directly to their higher hydration capacity (difra4sorghum4maize starch) and swelling property was 1.5 min and 2.5 min, respectively, with a friability of 0.32%. The effect of lubrication on the DT and friability of tablets containing maize and difra starch was significant (p50.05). However, more than 90% drug was released in vitro dissolution studies. Conclusion: Difra starch can replace maize and sorghum starch as tablet excipient.
Disintegration time, hydration capacity, lubrication sensitivity, swelling capacity, tablet compression, tensile strength, wet granulation
Introduction Active pharmaceutical ingredients should have optimum compressibility, flow properties, stability, and dissolution characteristics to be manufacturable and produce the intended pharmacological action. However, they do not possess these attributes per se and hence excipients are incorporated in the solid dosage formulations. An excipient when used alone cannot impart all these characteristics; therefore, multiple excipients are included in a formulation. Co-processed mixtures are now available commercially as mixtures of excipients that provide performance advantage which are otherwise not achieved by admixing the same composition (Block et al., 2009). For example, co-processed excipient mixture of microcrystalline cellulose, mannitol, and hydroxypropyl cellulose prepared by high shear mixing exhibited good or better pharmaceutical filler characteristics
Correspondence: Dr. Naseem Ahmad Charoo, Xepa-Soul Pattinson Sdn Bhd, 1-5 Cheng Industrial Estate, 75250 Melaka, Malaysia. Tel: +60 1 42361872. E-mail: [email protected]
History Received 18 June 2013 Revised 1 November 2013 Accepted 23 November 2013 Published online 19 February 2014
compared to lactose and calcium phosphate formulations (Jian-Xin et al., 2008; Sherwood et al., 1996; Westerhuis et al., 1996). Starch is a multipurpose excipient identified as one of the top 10 excipients in a joint conference on excipients (Shangraw, 1992). Corn starch is the most commonly used type of starch used in solid dosage formulations (Shangraw, 1992). Native starches obtained from breadfruit and cocoyam have also shown promise for their use in solid dosage forms (Adebayo & Itiola, 1998a,b). The binding and disintegrant properties of sorghum and plantain starches have been investigated (Adebayo & Itiola, 1998a,b; Kottke & Rhodes, 1991; Rowe, 1989). Corn starch is mainly used in the form of a paste in wet granulation process and its utility as a binding agent for hydrophobic drugs has been proven (Rowe, 1989). Adebayo and Itiola (1998b) reported superior hydration and moisture sorption capacities of breadfruit and cocoyam starches as compared to corn starch. These properties impart suitable characteristics to these starches making them useful mucilaginous binding agents. Various brands of corn starch were found to have insignificant effect on dissolution profiles of drugs (Kottke & Rhodes, 1991).
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However, starch from different botanical sources produced pastes with different characteristics due to variation in amylase–amylopectin ratio, which resulted in different binder substrate interactions (Alais & Linden, 1999). Moisture content of starch depends on its storage condition. Due to its effect on viscoelasticity, the compressibility of starch is determined by this residual moisture content (Rees & Tsardaka, 1994). At about 10% of moisture content, the tablets exhibit maximal binding characteristics (Bos et al., 1987). Even though native starches possess good compression properties but poor flow precludes their use as dry binders in direct compression formulations (Jivraj et al., 2000). Further, due to their plastic deformation, starches exhibit high lubricant sensitivity (Jarosz & Parrot, 1984). Povidone is a polymeric binder used mainly in the wet granulation process. On hydration, it produces viscous and tacky solution which binds the granules together. It is also added as a powder to the blend and then activated by solvent in situ. However, several technical problems such as over granulation problems, tablet hardening, and decrease in dissolution are associated with its use in granulation (Anonymous, 2009; Moore & Flanner, 1996). Povidone and starch in a dosage form may provide advantages of both good compaction and disintegration characteristics. The climate and fertile soil of Sudan are favorable for growing different types of starch such as wheat, corn, sorghum, and potato. Sudan rates among the leading producers of sorghum starch in Africa with annual production of 4 470 000 MT (21% of total production in Africa). Echinochloa colona (L.) Link (Poaceae) (syn. Panicum colonum) difra grass grows annually in small tufts to approximately 60 cm height mainly in the Kordofan and Darfur region (Dalziel, 1948). The seeds are harvested in the month of August, September, and October and ground to prepare flour for consumption as Asida and Kisra. The present study develops a formulation composition with locally grown difra starch having sufficient interparticle cohesive strength needed for commercial production of tablets with the desired attributes. The comparative binding, disintegrant efficacy, and lubricant sensitivity of difra starch versus other commonly used starch excipients in a tablet formulation containing povidone and prepared by wet granulation technique was also studied. Suitability of difra starch for use as a table excipient can obviate the need for local pharmaceutical and food industry to import expensive starch. In addition, it can open new avenues for exporting starch to the wider African region.
Materials and methods A gift sample of paracetamol, polyvinyl pyrrolidone (PVP), maize starch, magnesium stearate, croscarmellose sodium, and sodium starch glycolate was received from Blue Nile Pharmaceutical Company, Khartoum, Sudan. Native starches were purchased from local market and extraction process was carried out by the authors in the laboratory. All other chemicals and solvents were of analytical grade. JMPÕ (SAS Campus Drive, Building T, Cary, NC) software was used to perform ANOVA (results with p values, 0.05 were considered significant) and generate graphs.
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Table 1. Experimental design for preliminary experiments with different binders. Factors Run
F1 (wet massing time)
F2 (povidone)
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12
þ1 (12) 1 (4) þ1 (12) 0 (8) þ1 (12) 0 (8) 1 (4) 1 (4) þ1 (12) 0 (8) 1 (4) 0 (8)
þ1 (15) þ1 (15) þ1 (15) 1 (9) 1 (9) þ1 (15) 1 (9) þ1 (15) 1 (9) 1 (9) 1 (9) þ1 (15)
F3 (starch) þ1 þ1 1 þ1 1 1 þ1 1 þ1 1 1 þ1
Tablet weight (mg)
(30) (30) (15) (30) (15) (15) (30) (15) (30) (15) (15) (30)
298 298 283 292 277 283 292 283 292 277 277 298
The figures in brackets show the actual quantities used.
Preliminary experiments with different binders Three factorial experimental design (2 2 3) was adopted to evaluate the effect of corn starch and PVP binders at two levels each and the wet massing time at three levels as shown in Table 1. The batch size in all the runs was 157 g. The specified amount of paracetamol and PVP was sifted through BSS (British Standard Sieve Series; Filterwel Test Sieves, Mumbai, India) # 30 and mixed in a planetary mixer (Cnum5ST, Bosch- Ljubljana, Solvenia) for 10 min at 47 rpm. Starch slurry was prepared by dispersing it in 15 mL of cold water. Approximately 40 mL hot water heated at 90–100 C for 30 min was added to the starch slurry while continuously stirring it to obtain a smooth starch paste. The cooled starch paste was added to the mixture of paracetamol (250 mg/tablet) and PVP. The starch paste vessel was rinsed further with 3 mL water and added to the mixture. The granulation process was performed at 47 rpm for the specified time with a stopover at one-third and two-third of time to scrape the blades and sides using spatula. The wet mass was then screened through BSS# 12 sieve and dried at 40–50 C for 1 h or more till loss on drying (LOD) (105 C for 10 min) was less than 5% w/w. The dried granules were passed through BSS # 20. The granules were lubricated with 1% w/w magnesium stearate for 2 min and then compressed into tablets using a single punch tableting machine (Erweka Type EP-1, Heusenstamm, Germany) with a punch diameter of 9 mm and a compression force of 4–8 KP. Similarly the effect of superdisintegrants sodium starch glycolate (7.5 and 15.0 mg/tablet) and croscarmellose sodium (7.5 and 15.0 mg/tablet) on the optimized tablet composition was evaluated in a two factorial experimental study using the same process as provided above except disintegrant was added in equal proportions in intra and extra granular portions. Compressional characteristics of tablets prepared with native starches grown in Sudan in comparison with tablets prepared with commonly used maize starch The effect of difra starch, grown in Sudan, on binding and disintegration properties of paracetamol tablets was evaluated against the commonly used maize and sorghum starch.
Comparative binding of difra
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Starch type was the only variable in tablet compositions, which were prepared with the same procedure as outlined above. The starches were extracted using the following procedures. (a) Extraction of starch from pearl millet (Ashana variet; Pennisetum glaucum (L.)R. Br., (Poaceae) and Sorghum bicolor (L.) Moench (Poaceae) The starch was extracted from the two grains according to a combination of methods (Abdalla et al., 2009; Beleia et al., 1980). To inhibit microbial growth, millet grains were soaked at 4 C for 24 h in distilled water containing 0.01% sodium azide. Grains were then washed several times with distilled water, wet-milled in a blender for 3 min and screened through 200 mesh sieve. The process of wet-milling was repeated until no more starch could be separated. The starch suspension was centrifuged (Labspin-TC450C, Eltek, Mumbai, India) at 626 g for 20 min and the upper nonstarch layer was removed with spatula and discarded. The starch (lower layer) was suspended in water, centrifuged, and the tailings were scraped with spatula. The last step was repeated until a white prime starch (free of tailings) was obtained which was air-dried. The same procedure was followed for sorghum bicolor. (b) Extraction of starch from E. colona (difra) The method described in section (a) was used with slight modifications. The grains were first dehulled using a wooden mortar and pestle and washed several times with distilled water. The non-dehulled grains and any other foreign materials were isolated manually. The pure grains were soaked in distilled water containing 0.01% of sodium azide at 4 C for 24 h. Grains were then washed and treated by the same procedure used for obtaining starch from pearl millet and sorghum bicolor (c) Extraction of starch from cassava tubers The starch was extracted from root tubers of cassava [Manihot esculenta Crantz, (Euphorbiaceae)] according to the method of Yamini et al. (2011). Fresh cassava tubers were peeled, washed, and chopped into small pieces. The tubers were milled to a pulp using mixer and more distilled water was added to give dilute slurry which was sieved using 200 mesh sieve. This process was repeated until no more starch was extracted. The starch was precipitated out, washed many times, and the prime white starch obtained was air-dried. The starch was then passed through a 200 mesh sieve and evaluated for swelling and hydration capacity. Swelling capacity The swelling capacity of the three types of starches was determined by using the method of Olayemi et al. (2008) by running experiments in triplicate. Each starch (5 g) was accurately weighed and the tapped volume occupied by this amount (Vi) was noted. The powder was then dispersed in 85 mL of distilled water and the volume was made to 100 mL with the distilled water. After 24 h, the volume occupied by the sediment (Vf) was estimated for calculating swelling capacity. Swelling capacity ¼ Vf =Vi
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Hydration capacity One gram of each of starch powder (Y) was placed in a centrifuge tube and 10 mL of distilled water were added (Olayemi et al., 2008). The tube was shaken intermittently for 2 h and allowed to stand for 30 min before centrifugation for 10 min at 1409g in a bench centrifuge. The supernatant was decanted and the weight (X) of the powder after centrifugation was determined. Measurements were done in triplicate. The hydration capacity was calculated as Hydration capacity ¼ X=Y Compression properties and moisture uptake comparison of co-processed mixture prepared from different types of starch The co-processed mixtures of the optimized formulations were prepared by direct mixing and wet granulation techniques. Mixtures prepared by dry granulation were found to have insufficient compressibility. A direct mixture of starch (30 mg/tablet) and povidone (9 mg/tablet) was prepared by sifting them through BSS# 20 followed by mixing for 5 min at 12 rpm in octagonal blender (Erweka, Heusenstamm, Germany). Co-processed mixture by wet granulation was prepared by sifting starch and povidone through BSS#20. The mixture was granulated with water. The wet mass was passed through BSS# 12 and dried at 50–60 C in an oven. The dried granules were sifted through BSS #20 to break any lumps. Moisture uptake, particle size distribution, and angle of repose of mixtures were recorded. Moisture uptake This was determined by spreading 5 g sample uniformly in a Petri-plate. The samples were stored at room temperature and in a desiccator maintained at 25 C and 75% RH by saturated sodium chloride salt solution. The samples were withdrawn at predefined time intervals and conditioned at room temperature before weight gain was recorded. Comparative study of tablets containing difra starch with tablets prepared from corn starch, sorghum starch and cassava starch Maize starch in the optimized formulation was replaced with different types of starch and the physical characteristics of granules prepared by wet granulation using the same procedure as mentioned above were recorded. Tablets were evaluated for hardness (Caleva, model THT 500, Sturminster Newton, UK), compressibility index (Schwartz et al., 1975; Stanley-Wood & Shubair, 1979), weight uniformity reported as % CV (Mettler, AE 260, Mettler-Toledo, Switzerland), disintegration time (Erweka ZT 321, Heusenstamm, Germany), friability (Erweka, TA 120, Heusenstamm, Germany), and dissolution (Erweka type DT 800 low head, Heusenstamm, Germany) (USP, 2013). Fourier transform infrared spectroscopy: About 1–2 mg of test sample was triturated with 100 mg of potassium bromide and placed in the sample cup and made uniform with sample prodding bar. Infrared absorption spectrum in the range 400– 4000 cm1 was recorded at room temperature in Shimadzu FTIR instrument at a resolution of 1 cm1.
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Lubrication sensitivity Effect of lubricant (0.5%, 1.0%) and lubrication time (5 min; 10 min) on tablets prepared from different types of starches (maize, difra, and sorghum) was evaluated in a three factorial (3 2 2) experimental design study. Tablets were prepared by the same procedure as provided above and evaluated for DT, dissolution, and friability %.
Results and discussion
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Preliminary experiments with different binders The binding properties of polyvinyl pyrrolidone and binding/ disintegrant properties of corn starch were tested in the wet granulation process. The effect of wet massing time was also evaluated. The physical characteristics of the formulations are presented in Figure 1. At 12 min wet massing time, increase in povidone concentration led to increase in DT from 13 min (formulation 9) to more than 30 min (formulation 1). The % CV of formulations 2, 3, and 4 was 1.4, 0.52, and 0.71, respectively. The povidone was found to be better binder than starch. This was further confirmed by low friability % values of 0.97, 0.79, and 0.42, respectively, for these formulations. The low % CV and % friability are indicators of uniformity, good flow, and compressibility properties of the formulation mixtures. These parameters are essential for scale-up consideration.
DT decreased to 10 min and friability to 0.42% when starch (30 mg) and povidone (9 mg) in their highest and lowest concentrations, respectively, were mixed for 8 min in formulation 4. Starch at higher concentration showed better disintegrating properties as is evident from the contour plot (Figure 1). A further increase in mixing time had a negative effect on DT as was noticed in formulation 9, which disintegrated in 13 min. This deleterious effect on DT was more evident in formulations containing starch and povidone at their maximum levels. The DT increased from 25 min in formulation 2 to 36 min in formulation 1 with increased mixing time. At the same time, mixing time of 4 min was insufficient for effecting suitable binding as is evident from high % CV values of 2.41, 5.10, and 4.60 for formulations 7, 8, and 11, respectively. Granules of optimum strength can be produced only when the binder solution is uniformly distributed and spread on the powder blend. However, at higher mixing time, the granules tend to become harder and may fail in dissolution or pose challenges in compression. The effects of superdisintegrants sodium starch glycolate and croscarmellose sodium on compressional properties were evaluated in an experimental designed study. Sodium starch glycolate and croscarmellose sodium are modified starch and cellulose molecules formed by cross-linking of the organic chains. They swell on coming in contact with water and exert pressure in radial direction leading to disintegration of tablets. Other mechanisms involved in their disintegrant activity are
Figure 1. Physical characteristics of preliminary formulations.
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Figure 2. Response surface plots depicting effect of disintegrants on DT and % friability.
wicking, deformation recovery, and particle repulsion (Abu-lazza et al., 2004; Zhao & Augsburger, 2005). The DT was significantly reduced from 10 min to 2.2 min in formulations containing lower concentration of disintegrants. However, further increase in their concentrations did not affect DT significantly (p40.05, ANOVA followed by Tukey’s test). The response surface plots (Figure 2) elucidate the relationship between variables. Both the disintegrants had negative effects on percentage friability as they reduced the bonding force between the particles in the granules. The % friability increased to 1.5% from 0.42% when they were used at their highest levels. The first-order model equation obtained for the DT and friability % was DT ¼ 3:1 þ 0:9 ðcroscarmellose sodium concentrationÞ Friability% ¼ 1:175 þ 0:275 ðsodium starch glycolateÞ þ 0:225 ðcroscarmellose sodium concentrationÞ
The coefficient of the interaction was zero and the effect of sodium starch glycolate on DT was not noticed. The results obtained are similar to those reported by Quadir and Kolter (2006) who noted higher swelling pressure exerted by croscarmellose sodium as compared to sodium starch glycolate. Compression properties and moisture uptake comparison The Hausner ratios of co-processed mixtures prepared by direct mixing were 1.45, 1.81, and 1.38, respectively, for maize starch, difra starch, and sorghum starch. Similarly the Hausner ratios of mixtures prepared by the wet mixing process were 1.21, 1.26, and 1.19, respectively, for maize, difra, and sorghum starches. Hausner ratio and compressibility values below 1.25 and 25% indicated good flow characteristics imparted by the wet granulation process. The moisture uptake
capability of all the mixtures obtained by wet granulation under high humidity conditions was almost similar. The equilibrium moisture uptake of 8–9% was observed after 4 d of storage at 75% RH. The LOD values determined at 105 C for 20 min were 8.9, 7.8, and 8.7%, respectively, for co-processed mixtures obtained with sorghum, difra, and maize starch. Comparative study of tablets containing difra starch with tablets prepared from corn, sorghum, and cassava starch The effect of different starch grades on the compressional characteristics of paracetamol tablets was evaluated by replacing maize starch in the optimized formulation obtained above with its other grades. The bulk and tap density of all the starches were in the range of 0.47–0.51 and 0.63–0.68, respectively. Similarly, Hausner ratio and angle of repose values were 1.3–1.45 and 33–35, respectively. Hausner ratio indicated moderate flow characteristics of starches due to low inter-particulate friction (Sherwood et al., 1996). The results were confirmed by the Carr index values of 23–30; also, all the starches showed the similar particle size distribution (Figure 3). The tablet characteristics are shown in Figure 4. Regardless of the starch type, the friability in all the formulations was 0.32%. The DT of sorghum and difra starch formulations was 1.5 min and 2.5 min, respectively. The hydration capacity of sorghum, difra, and maize starch was 1.81, 1.90, and 1.46, respectively. Similarly their swelling capacity was 1.21, 1.28, and 1.07, respectively. The hydration capacity of an excipient determines water penetration which precedes tablet disintegration (Caramella, 1984). Swelling capacity of starch depends on its amylopectin content and the two are inversely proportional (Tester et al., 2004). The higher hydration and swelling capacity of sorghum and difra starch
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impart them good disintegration properties. Absorption of large quantities of water due to the higher swelling capacity of sorghum and difra starch would generate a higher swelling force leading to faster disintegration of the tablet (GuyotHermann, 1992). Our results are in agreement with the findings of Garr and Bangudu (1991) who reported that sorghum starch was as an effective binder as maize starch and exhibited about twice the disintegrant activity as compared to maize starch. In another study, sorghum starch
was found to have better binding and disintegrant properties than maize starch and better binding properties than acacia (Deshpande & Panya, 1987). Cassava starch has been found to possess superior binding property as compared to cocoyam starch and maize starch due to higher gel strength of its mucilages (Uhumwangho et al., 2006). However, the DT of tablets tends to increase which explains the high DT (7 min) of tablets prepared from cassava starch (Figure 5). The FTIR spectra of the final dosage forms were almost a superposition of the spectra of starch, PVP, and paracetamol (figure not shown). The presence of the same bands suggests the absence of any chemical interaction.
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Lubrication sensitivity
Figure 3. Particle size distribution of blends prepared by suing starch from different sources.
Starch undergoes plastic deformation and may be sensitive to high lubricant concentration. As shown in Figure 4, the effect of magnesium stearate concentration and lubrication time on DT and the % friability of sorghum starch was insignificant (p40.05). With the increase in magnesium stearate concentration and mixing time from 0.5% and 5 min to 1% and 10 min, respectively, the DT of formulations containing difra starch increased from 3.55 to 7 min, respectively (p50.05). Friability % values also increased to 1.6% from 1% indicating the synergistic effect of lubrication time and magnesium stearate concentration. However, no effect on dissolution was observed as 490% drug release was observed after 10 min (Figure 6). The effects of boundary lubricants like magnesium stearate are more pronounced in excipients exhibiting plastic
Figure 4. Effect of lubrication on tablet DT and % friability.
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Figure 5. Effect of different types of starch on DT and weight variation.
deformation (Hussain, 1990). The higher plasticity of difra starch may contribute in its sensitivity to magnesium stearate concentration and lubrication time. As deduced from Figures 4 and 6, the lubricants can be used at lower concentrations and lubrication time should be maintained below 5 min, similar results were obtained with maize starch formulations. The DT almost doubled to 10.24 min with an increase in magnesium stearate concentration and lubrication time; however, more than 88% drug was released after 10 min. The tensile strength of tablets increased with the increase in compression force. The tensile strength of tablets prepared from maize, difra, and sorghum starch containing 0.5% lubricant, lubricated for 5 min, and compressed at 3 KN was 0.91, 0.92, and 0.74, respectively (Figure 7). Tablets of higher
strength were obtained from blends containing difra and maize starch.
Conclusion Difra starch has many suitable attributes as tablet excipient and can replace conventional maize and other types of starch excipients. It exhibited good compressibility and fast dissolution behavior. The powder properties were similar to maize and sorghum starch. Moisture uptake capabilities at higher humidity conditions were also similar. The tabletting behavior of starches was also comparable. Tablets prepared from sorghum and difra starch demonstrated lower DT values. The advantage of fast disintegration will translate into fast drug
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Figure 6. Effect of lubrication on drug release. Key: formulations: 1 ¼ 1 þ þ; 2 ¼ 1 þ; 3 ¼ 1 þ ; 4 ¼ 1 ; 5 ¼ 2 þ þ; 6 ¼ 2 þ; 7 ¼ 2 þ ; 8 ¼ 2 ; 9 ¼ 3 þ þ; 10 ¼ 3 þ ; 11 ¼ 3 þ ; 12 ¼ 3 ; ‘‘1’’, sorghum starch; ‘‘2’’, difra starch; ‘‘3’’, maize starch; ‘‘þ’’, high lubricant concentration; ‘‘’’, low lubricant concentration; ‘‘þ’’, high lubrication time; ‘‘’’, low lubrication time.
Figure 7. Effect of lubrication on tensile strength of tablets prepared from different starch types.
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dissolution as seen in drug release studies. No interaction with drug or excipients was observed. Tensile strength of tablets prepared with difra starch was better than sorghum starch and comparable to maize starch tablets. The results of these studies have established that difra starch has excellent binding and disintegrant properties.
Declaration of interest The authors report no declaration of interest.
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