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Compactibility and compressibility studies of Assam Bora rice starch
Powder Technology 224 (2012) 281–286
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Powder Technology journal homepage: www.elsevier.com/locate/powtec
Compactibility and compressibility studies of Assam Bora rice starch Mohammad Zaki Ahmad a, Sohail Akhter b, Mohammed Anwar b, Mahfoozur Rahman a, Mohammad Ahsan Siddiqui b, Farhan Jalees Ahmad b,⁎ a b
Dreamz College of Pharmacy, Khilra-Meramesit, Mandi-175036, India Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard University, New Delhi-62, India
a r t i c l e
i n f o
Article history: Received 4 November 2011 Received in revised form 2 March 2012 Accepted 3 March 2012 Available online 9 March 2012 Keywords: Assam Bora rice starch Tableting properties Direct compression Lubricant sensitivity Heckel analysis Kawakita plot
a b s t r a c t A comparison study was made on the powder flow characteristics, tableting properties of experimental Assam Bora rice starch, obtained from the variety Aghuni Bora of Oryza sativa and the mechanical properties of tablets made up of it with those of official Starch 1500®. The influences of physical and geometrical properties of both the starch were evaluated with regards to their compression properties. It has been found that Assam Bora rice starch reflects better physical characteristics such as higher bulk and tap densities, less porosity, better powder packing ability, minimum lubricant sensitivity, large surface area and improved flowability. Apart from that the mechanical properties, such as toughness and Young's modulus of Assam Bora rice starch were also compared with that of Starch 1500®. It has been also brought into result that compactibility of Assam Bora rice starch was not affected by the blending time. Further compaction properties of the experimental starch were evaluated by using Kawakita and Heckel equations and compared well with those of Starch 1500 ®. The result obtained shows that it mainly deforms by plastic deformation. Their onset of plastic deformation and strain rate sensitivity as compared to that of Starch 1500® demonstrates its potential use as a direct compression filler-binders. © 2012 Elsevier B.V. All rights reserved.
1. Introduction Tablet manufacturing is a tedious task, encompassing the wet and dry granulation methods especially due to the involvement of a series of unit operations as well as the potential cost consideration. A more possible attractive interest and option for manufacturing of tablets by direct compression (DC) by the pharmaceutical industry is due, to its cost effectiveness as it requires fewer processing steps, stability towards moisture and heat, faster dissolution, less wear and tear of punches and simplified validation to meet the requirement of current good manufacturing practices [1]. The availability of new excipients, newer grades of existing excipients and advanced mechanized technology such as positive die feeding and precompression stages has led to a perceptible shift of direct compression process towards the tablet manufacturing technology. Several directly compressible vehicles (DCVs) with free flow and better compaction properties have been developed in recent years [1–7] and still many others are under development for better performance. As a result, many excipients have been introduced for the last five decades to the pharmaceutical market as filler-binders for tablets, prepared by direct compression. Starches and their derivatives from several natural resources are
⁎ Corresponding author. Tel.: +91 9810720387. E-mail address: [email protected] (F.J. Ahmad). 0032-5910/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.powtec.2012.03.004
extensively investigated for their well known and safety application in formulation development of tablets for various purposes. On answering to this investigation towards several natural starches, rice starch have proved to be much better compaction properties as compared to potato, maize and tapioca starches for the manufacturing of tablets [8]. Assam Bora rice, locally known as Bora Chaval is widely distributed throughout upper Assam in North East region of India, characterized by its high amylopectin contents, and was first introduced in Assam from Thailand or Myanmar by Thai-Ahoms [9–13]. The potential use of Assam Bora rice starch in the formulation of matrix tablet and compression coated tablet for colon targeting has been previously reported by Ahmad and co-workers [10,11]. The current study focuses upon the performance and tableting properties of Assam Bora rice starch as a directly compressible vehicle in contrast to commercially available direct compression excipient, Starch 1500 ®.
2. Material and methods 2.1. Materials Assam Bora rice was procured from the local villagers of Dibrugarh district of upper Assam. Starch 1500 ® was kindly supplied by Anshul Agencies, Mumbai as a gift sample. All other chemicals were of analytical reagent grades.
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2.2. Methods 2.2.1. Isolation of starch from Assam Bora rice Starch was isolated from Assam Bora rice variety Aghuni Bora as per the process described by Ahmad et al. with slight modification [11–14]. About one part of broken rice (fruits of Oryza sativa, family Gramineae) was steeped in two parts of 0.01 M sodium hydroxide solution. The mass was stirred every 1 h and liquor changed every 2 to 3 h. The process was completed, when rice grain was crushable between the fingers. This treatment loosens and partially dissolves the glutinous matter, which holds the starch together. The steeped rice was milled in a mixer grinder with two parts of double distilled water to each part of steeped rice to get milky fluid; it was then diluted with distilled water until it contained about 2–3% of solid. Resulting starch suspension was passed through series of sieves # 20, #44, #80, and #120 respectively. The thick starch suspension was allowed to settle in a 1000 ml beaker. It was then repeatedly washed with 0.0125 M NaOH until the supernatant solution was clear and finally washed with freshly prepared double distilled water to remove the alkali completely. The starch was then concentrated by using a rotary evaporator and dried slowly in hot air oven at 40 °C for 36 h. It was then passed through sieves # 80 and stored in tightly closed container. Isolated starch was characterized by their particle size distribution, flow properties and compressibility analysis. 2.2.2. Particle size and size distribution The size distribution and shapes of the starch were determined by optical microscopy. On approximately 500 starch particles were picked randomly in the optical field of starch powders, from which values of mean projected diameter (dp) were calculated. Heywood diameter (de) was determined using an image processor (Image Hyper 700 II; Japan), by calculating the diameter of circle whose area was equivalent to the actual projected area A of a particle, as shown by Eq. (1) [15]
Diameter de
! rffiffiffi 4 AreaðAÞ π
ð1Þ
Geometric mean diameters (dg) were determined from the lognormal distribution plot of particles mean diameter versus cumulative percent frequency [16,17]. Surface areas of the particles were determined by Quantasorb surface area analyzer (Model QS-7). Helium gas was used as carrier and diluent gas, while nitrogen gas was used as adsorbate. Studies were conducted at relative pressure (P/Po) ranging from 0.05 to 0.30 and specific surface areas (SSABET) were obtained by BET equation [16]. 2.2.3. Powder properties The flow properties of the samples were investigated by the angle of repose, bulk density, and tapped density measurements [16]. The angle of repose was determined on 50 g of sample using a Borosilicate glass funnel (with an orifice diameter and a base diameter of 6.5 mm and 8 cm, respectively). Bulk and tapped densities were measured in 100 ml of a graduated cylinder. The sample contained in the cylinder was tapped mechanically by means of Auto-Tap Shaker (Quantachrome Instruments, USA). The tapped volume was noted down when it showed no change in its value. The data generated from bulk densities and tapped densities were used in computing the Carr's compressibility index and Hausner's ratio for the starches [16]. True density was obtained on a helium pycnometer (Ultrapyc 1200e Helium Pycnometer, Quantachrome Instruments, USA). The data generated from bulk density and true density were utilized for calculating the porosity of powder mass. Moisture content was determined by official method of USP32-NF27 in a mechanical convection oven (Remi Scientific, Bangalore) at 105 °C to the weight constants.
2.2.4. Preparation of tablets 500 mg of each powder (Assam Bora rice starch and Starch 1500 ®) was directly compressed by using 12 mm diameter flat-faced lubricated punch and die set installed in 16 station Cadmach tablet machine (Cadmach, Ahmadabad, India). Tablets were prepared under conditions where maximum compression pressure P ranged from 10 to 250 MPa and the rate of compression was kept constant at 0.03 cm/s. The compression pressure was released immediately after the pressure reached P. After ejection, the tablets were stored over silica gel for 48 h to allow elastic recovery and hardening and to prevent falsely low yield values [18]. 2.2.5. Compactibility analysis After 48 h, final thickness (Tt) and diameter (Dt) of the normal tablet and the tablets with hole (To, Do) were measured and the results obtained was used to determine tablet tensile strength (T) by diametric compression test (TBH30, Erweka, Heusenstamm, Germany) and by applying Eq. (2) [15] T¼
2H πDt Tt
ð2Þ
H = applied load needed to cause the fracture. Results were taken only from those tablets which showed no sign of lamination or capping and split cleanly into two halves. Packing fraction of the tablets (Pt) was obtained by applying Eq. (3) [15] Pt ¼
ρr ρs
ð3Þ
ρr is relative density of the tablets and ρs is true density of powders respectively. ρr was calculated by using Eq. (4) [15]. ρr ¼
Wt ðDt =2Þ2 πTt
ð4Þ
Wt = weight of the tablets. The results obtained from tensile strength versus the product of the solid fraction and the compression pressure was fitted according to the Leuenberger model [19,20] in Eq. (5) ð−γ Pρr Þ T ¼ TMax 1−e c
ð5Þ
Tmax is the theoretical tensile strength at infinite compression pressure; γc is the compression susceptibility parameter (MPa − 1). Data fitting was performed employing the Statgraphic® software (Stat Point Technologies). 2.2.6. Brittle fracture index, Young modulus and toughness 500 mg of each powder was directly compressed into the tablets with hole of 1.5 mm diameter at their center by using an upper punch with a hole through the center and a lower punch fitted with pin (12 mm diameter). After ejection, the tablets were stored over silica gel for 48 h and the resulting stress–strain curves were obtained on a universal stress–strain analyzer ( Q-test-I ®, Material testing system NC, USA). The Young's modulus was obtained from the slope of the stress–strain curves. It measures the stiffness of the material. The toughness of the material was obtained by measuring the area under curves of the resulting stress–strain curves. The brittle fracture index (BFI) was calculated from Eq. (6) [21] BFI ¼ 0:5
T −1 To
ð6Þ
where T is the tensile strength of normal tablet and To is the tensile strength of the tablet with hole.
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2.2.7. Lubricant sensitivity Lubricant sensitivity analysis was performed by the method described by Rojas et al. [19] with slight modification. Starch powders and magnesium stearate (1% w/w) were mixed using a double cone blender for 5 to 60 min. After mixing, the powder mass was passed through ASTM (American Society of Testing and Materials) 80 mesh sieves. Tablets of 500 mg were compressed at 75 Mpa compression pressure. In the similar fashion another batch of tablets were prepared without lubricants. Lubricant sensitivity (LS) was determined by Eq. (7) LS ¼
Fo −Flub Fo
ð7Þ
Flub and F0 are the hardness of the tablets prepared with and without lubricants. Hardness test was performed on the hardness tester (TBH30, Erweka, Heusenstamm, Germany). 2.2.8. Compressibility analysis The Kawakita equation is used to study the powder compression using the degree of volume reduction (C) and is written as [22] Vo −Vp ¼ abP=ð1 þ bPÞ Vo
C¼
and ρa can be calculated from Eq. (13) ð8aÞ A ¼ ln
or F F 1 ¼ þ C a ab
ð8bÞ
In the foregoing equation, V0 denotes the initial volume of powder bed and VP is the powder volume after compression. The terms a and b are constants, a is equal to minimum porosity of the material before compression representing the compressibility index and is related to the total volume reduction for the powder bed, while b represents the plasticity of material and is related to the resistant forces (Friction/ Cohesion) to compression [19] Compression behavior of powders was characterized by Heckel plots [23] by using Eq. (9) ln
1 1−ρr
¼ KP þ A; ε ¼ 1−ρr
ð9Þ
where ρr is the relative density of the compact at pressure P, ε is the porosity of powders, and K and A are constants. It represents the powder densification by die filling and particle rearrangement before deformation and bonding of discrete particles take place. The slope of the straight line, K is reciprocal of the mean yield force, PY of the material. ε is the porosity of powder bed. Densification of a powder by die filling is expressed by Eq. (10) [23–25]. ln
1 1−ρo
ð11Þ
Here B describes the volume reduction by particle rearrangement. Relative densities corresponding to the processes above are ρa, which includes both die filling and particle rearrangement and ρb, which describe the extent of particle rearrangement. The relative densities can be related by Eq. (12) ρ a ¼ ρo þ ρb
1 1−ρa
ð13Þ
2.2.9. Statistical analysis The student t test was used to find the statistical significance. A value of P b 0.05 was considered statistically significant. All tests were performed in the replicate of 10 independent samples. 3. Results 3.1. Particle size and size distribution The size distribution of the Assam Bora rice starch and Starch 1500 ® was 25–120 μm and 30–150 μm respectively (Fig. 1). The results of physical and geometric properties of the starches are presented in Table 1. The projected diameter of the Assam Bora rice starch is 12 ± 1.320 μm, whereas for Starch 1500 ® this value is 9 ± 1.061 μm. The result was found to be statistically significant (P b 0.001). 3.2. Powder properties The flow properties of the samples were investigated by the angle of repose, bulk density, and tapped density measurements, Carr's compressibility index, Hausner's ratio and porosity, are summarized in Table 1. The result was found to be statistically significant (P b 0.001).
ð10Þ
where ρo is the relative density of a powder and usually derived from the bulk density. The combined effect of die filling and particle rearrangement at low pressure can be described by Eq. (11) 1 A ¼ ln þB 1−ρo
Fig. 1. Particle size distribution of Assam Bora rice starch and Starch 1500® (n = 500).
ð12Þ
Table 1 Powder characteristics and flow properties of Assam Bora rice starch and Starch 1500®. Properties
Assam Bora rice starch
Starch 1500®
dp (μm) de ((μm) dg (μm) SSABET (m2/g) Angle of repose (degree) Compressibility index (%CI) Hausner's ratio (H) Bulk density (ρb) Tapped density (ρt) True density (ρp) % Porosity (ε) %Moisture content
12 ± 1.320 15.67 ± 0.46 58.7 ± 2.050 10.5 ± 0.670 23.02 ± 1.01 15.92 ± 1.23 1.18 ± 0.001 0.586 ± 0.01 0.697 ± 0.03 1.57 ± 0.23 62.67 ± 2.34 4.31 ± 0.78
9 ± 1.061 13.12 ± 0.02 69.9 ± 5.09 6.8 ± 1.43 27.09 ± 0.08 17.16 ± .045 1.20 ± 0.002 0.579 ± 0.001 0.689 ± 0.002 1.53 ± 0.067 63.15 ± 4.67 9.87 ± 1.09
All values are expressed as mean ± s.d., n = 10.
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Table 2 Results obtained from compactibility analysis, brittle fracture index, young modulus and toughness. Sample
AUCT (MPa2)⁎
Tmax (Mpa)⁎
γc (Mpa- 1)
BFI⁎
Young modulus⁎
Maximum stress (MPa)⁎
Maximum strain (%)⁎
Toughness (MPa)⁎
Lubricant sensitivity⁎
Assam Bora rice starch Starch 1500®
2438.7 ± 50.32 1663.4 ± 25.56
43.98 ± 2.54 21.78 ± 3.56
0.004 0.006
0.962 ± 0.006 1.234 ± 0.034
0.31 ± 0.005 0.26 ± 0.001
5.13 ± 0.236 3.73 ± 0.372
1.89 ± 0.31 1.67 ± 0.03
892 ± 19.09 786 ± 13.67
0.31 ± 0.01 0.53 ± 0.03
⁎All values are expressed as mean ± s.d, n = 10.
Fig. 2. Tensile strength of compact prepared from Assam Bora rice starch and Starch 1500® at different compression pressures.
3.3. Compactibility analysis The results from Leuenberger model for tensile strength are presented in Table 2. The compactibility expressed as the area under the tensile strength (AUCT) of Assam Bora rice starch was about 1.5 times greater than that of Starch 1500 ®. Tmax for the Assam Bora rice starch is higher than Starch 1500 ®. The compression susceptibility value for Assam Bora rice starch is smaller than Starch 1500 ®. Effect of compression pressure on the tensile strength of compact is presented in Fig. 2. 3.4. Brittle fracture index, Young modulus and toughness BFI obtained from Eq. (6) is presented in Table 2. The lowest BFI was observed for Assam Bora rice starch (0.962 ± 0.006) than Starch 1500 ® (1.234 ± 0.034). The value of Young's modulus for Assam Bora rice starch and Starch 1500® varies from 0.31 ± 0.005 to 0.26 ± 0.001 respectively. The toughness of the materials was obtained by measuring the area under curves of the resulting stress–strain curves. Toughness value for the tablet from Assam Bora rice starch and Starch 1500® varies from 892 ± 19.09 to 786 ± 13.67 Mpa respectively.
for the Assam Bora rice starch and Starch 1500 ® varies from 0.63 to 0.58 respectively. The “b” parameter obtained from Kawakita analysis is lower for the Assam Bora rice starch. The value of yield pressure (Py) of Assam Bora rice starch is comparable to Starch 1500®.
4. Discussion 4.1. Particle size and size distribution Particle size and surface area always play a vital role for the release of drug from its dosage form. Greater surface area brings about intimate contact of the drug with dissolution fluid in-vivo and enhances the drug solubility and dissolution. Assam Bora rice starch shows uniform particle size distribution. The specific surface area is used to describe the area of contact between the particles. The specific surface area obtained by the BET analysis showed that Assam Bora rice starch had larger surface areas than Starch 1500®. The larger the specific surface area and smaller is the particle size, the larger the area of contact between the particles. This observation is true for Assam Bora rice starch.
3.5. Lubricant sensitivity Lubricant sensitivity was tested against Magnesium stearate at 1% w/w level. The trend for lubricant sensitivity was observed as Starch 1500 ® > Assam Bora rice starch. Lubricant sensitivity and blending time of the Assam Bora rice starch and Starch 1500 ® are presented in Figs. 3 and 4 respectively. 3.6. Compressibility analysis Table 3 shows the parameters resulting from the different compression models employed. The compressibility index i.e. “a” for the Assam Bora rice starch is close to the values of its porosity. The value of “a”
Fig. 3. Lubricant sensitivity of Assam Bora rice starch and Starch 1500®.
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Fig. 4. Effect of blending time and lubricant sensitivity of Assam Bora rice starch and Starch 1500®.
4.2. Powder properties Angle of repose, compressibility index and Hausner's ratio collectively constitute the simple, fast and popular mean of predicting flow properties, were chosen for flow characterization. Corresponding values indicate good flow property (USP34-NF29). It may be due to its high densification, more regular morphology and reduced porosity. Assam Bora rice starch presented higher bulk and tap densities than Starch 1500 ®. This phenomenon is due to its lower particle size and higher consolidation achieved during process. Thus, Assam Bora rice starch exhibits a more regular, smooth and almost spherical particles, which were more compactable than Starch 1500 ®. Porosity of Assam Bora rice starch and Starch 1500® varies from 62.67 ± 2.34 to 63.15 ± 4.67 respectively. In this case, regular, smooth and almost spherical shape of the Assam Bora rice starch made packing more convenient and hence its porosity was reduced. Moisture content of Assam Bora rice starch is significantly less as compared Starch 1500®. This is due to fact that pregelatinized starch i.e. Starch 1500® is hygroscopic. 4.3. Compactibility analysis The compression susceptibility (γc) was lower for Assam Bora rice starch than Starch 1500 ®. Further compactibility expressed as the area under the tensile strength of Assam Bora rice starch and Starch 1500 ® varies from 2438.7 ± 50.32 to 1663.4 ± 25.56 respectively. The predicted maximum tensile strength value (Tmax) for the Assam Bora rice starch is about two fold greater than that of Starch 1500 ®, thus better compactibility than Starch 1500 ®. 4.4. Brittle fracture index, Young modulus and toughness The brittle fracture index is a measure of the ability of a tablet to relieve stress that is caused by the presence of defective region (hole) [19]. Since a low value of BFI is desirable for minimizing the lamination and capping of tablet, therefore, in this regard Assam Bora rice starch would be more useful. Young's modulus measures the stiffness of the material i.e. the resistant of the material to elastic deformation when it is compressed. Assam Bora rice starch had a higher Young modulus than Starch 1500®, indicating a high resistance to elastic deformation. Table 3 Parameter derived from Kawakita and Heckel analyses of Assam Bora rice starch and Starch 1500®. Sample
Assam Bora rice starch Starch 1500®
Kawakita parameters
Heckel parameters
a
B
Py
ρa
ρb
ρo
0.63 0.58
0.14 0.20
81 78
0.61 0.59
0.58 0.57
0.15 0.18
The toughness of the material represents the resistance when compressed until breaking [19,26]. Tablets prepared from Assam Bora rice starch can withstand a minimum of 6 Mpa compression force before breaking, while the value for the tablets prepared from Starch 1500® was 2.5 Mpa. The large toughness value indicates the increased ability of Assam Bora rice starch to absorb and withstand applied force. 4.5. Lubricant sensitivity Magnesium stearate is commonly used in tablet formulations to reduce friction between the material and tooling used. Starch 1500 ® is known for having high sensitivity to lubricants [27]. These results suggest that materials with low Py value are more sensitive to magnesium stearate, and thus sensitivity decreases as the ductility of the material decreases. As seen in Fig. 3, the trend for lubricant sensitivity ranged as: Starch 1500 ® > Assam Bora rice starch. Fig. 4 shows the relationship between blending time and lubricant sensitivity. In case of Assam Bora rice starch, a plateau in sensitivity is achieved within 25–30 minutes of blending. This suggest that covering effect of Magnesium Stearate reaches a limit between 25and 30 min and new available sites for particle binding are formed afterwards. Long mixing time with lubricant had a major effect on the lubricant sensitivity of Starch 1500 ®. 4.6. Compressibility analysis To clarify the change in the tableting properties of the Assam Bora rice starch and Starch 1500 ®, the compression behavior was analyzed by developing the Kawakita equation and Heckel analysis. Kawakita analysis showed comparable total compressibility “a” values from Assam Bora rice starch and Starch 1500 ®. Furthermore “b” parameter showed that Assam Bora rice starch is the material with lowest cohesive forces to compression. Thus compressibility range follow the order Assam Bora rice starch > Starch 1500 ®. Since Assam Bora rice starch has the high volume reduction, it also had highest compactibility and theoretical tensile strength. Yield pressure (Py) of the Assam Bora rice starch and Starch 1500 ® are comparable indicating a similar onset of Plastic deformation under compression. Since in both sample ρb is larger than ρo, thus densification through particle rearrangement was more widespread than die filling at lower compression pressures. 5. Conclusion This study demonstrated the promising use of Assam Bora rice starch as direct compression agent/excipients. Assam Bora rice starch exhibited good flow properties. Results connote that Assam Bora rice starch would be more useful in minimizing the problems of lamination and capping especially on high speed tableting machine with short dwell time for the plastic deformation of material while on the other hand,
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Fig. 5. Tablet prepared from Assam Bora rice starch by direct compression.
it would be more useful when high tensile strength of the tablet is desirable (Fig. 5). Assam Bora rice starch can be used in the formulation of Amine drugs; this is due to the fact that very low moisture content of Assam Bora rice starch will reduce the chance of Maillard reaction. Thus, Assam Bora rice could be worthful in the formulation development of tablets with desirable compaction and mechanical properties for particular, specialized and/or versatile purposes. Acknowledgement The authors thank H Dubey, General Manager, R & D, Oil India Ltd, Duliajan, Assam, India for providing the instrument facility. They also thank HC Das, R Bordoloi and PK Borah of Oil India for cooperation in the laboratory and for providing the facilities to carry out parts of this investigation. References [1] A.H. Nada, E. Graf, Evaluation of Vitacel M80K as a new direct compressible vehicle, European Journal of Pharmaceutics and Biopharmaceutics 46 (1998) 347–353. [2] A.B. Bangudu, N. Pilpel, Tensile strength of paracetamol and avicel powders and their mixtures, Journal of Pharmacy and Pharmacology 36 (1984) 717–722. [3] L.J. Tasic, A. Galetin, J. Marjanovic, The influence of diluents on the physical characteristics of paracetamol tablets, Pharmazie 48 (1993) 865–866. [4] P. Gupta, S.K. Nachaegari, A.K. Bansal, Improved excipient by coprocessing functionality, in: A. Ashok Katdare, M.V. Chaubal (Eds.), Excipient Development for Pharmaceutical, Biotechnology, and Drug Delivery Systems, Informa Healthcare, New York, 2006, pp. 109–126. [5] E.J. Mendell, Direct compression methods of producing solid dosage forms, Manufacturing Chemist and Aerosol News 43 (1997) 43–46. [6] E. Wambolt, C. McKnight, M. Torkoglu, A. Sakr, Compression of two microcrystalline cellulose brands for the direct compression of hydrochlorothiazide tablets, La Pharmacie Industrielle 55 (1993) 1046–1051. [7] J.B. Schwartz, J.F. Bavitz, Direct compression vehicles/effect of common diluents on compression, Drug and Cosmetic Industry 116 (1976) 60–64. [8] C.E. Bos, G.K. Bolhuis, D.H. Van, C.F. Lerk, Native starch in tablet formulations: properties on compaction, Pharmaceutisch Weekblad. Scientific edition 9 (1987) 274–282.
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Powder Technology journal homepage: www.elsevier.com/locate/powtec
Compactibility and compressibility studies of Assam Bora rice starch Mohammad Zaki Ahmad a, Sohail Akhter b, Mohammed Anwar b, Mahfoozur Rahman a, Mohammad Ahsan Siddiqui b, Farhan Jalees Ahmad b,⁎ a b
Dreamz College of Pharmacy, Khilra-Meramesit, Mandi-175036, India Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard University, New Delhi-62, India
a r t i c l e
i n f o
Article history: Received 4 November 2011 Received in revised form 2 March 2012 Accepted 3 March 2012 Available online 9 March 2012 Keywords: Assam Bora rice starch Tableting properties Direct compression Lubricant sensitivity Heckel analysis Kawakita plot
a b s t r a c t A comparison study was made on the powder flow characteristics, tableting properties of experimental Assam Bora rice starch, obtained from the variety Aghuni Bora of Oryza sativa and the mechanical properties of tablets made up of it with those of official Starch 1500®. The influences of physical and geometrical properties of both the starch were evaluated with regards to their compression properties. It has been found that Assam Bora rice starch reflects better physical characteristics such as higher bulk and tap densities, less porosity, better powder packing ability, minimum lubricant sensitivity, large surface area and improved flowability. Apart from that the mechanical properties, such as toughness and Young's modulus of Assam Bora rice starch were also compared with that of Starch 1500®. It has been also brought into result that compactibility of Assam Bora rice starch was not affected by the blending time. Further compaction properties of the experimental starch were evaluated by using Kawakita and Heckel equations and compared well with those of Starch 1500 ®. The result obtained shows that it mainly deforms by plastic deformation. Their onset of plastic deformation and strain rate sensitivity as compared to that of Starch 1500® demonstrates its potential use as a direct compression filler-binders. © 2012 Elsevier B.V. All rights reserved.
1. Introduction Tablet manufacturing is a tedious task, encompassing the wet and dry granulation methods especially due to the involvement of a series of unit operations as well as the potential cost consideration. A more possible attractive interest and option for manufacturing of tablets by direct compression (DC) by the pharmaceutical industry is due, to its cost effectiveness as it requires fewer processing steps, stability towards moisture and heat, faster dissolution, less wear and tear of punches and simplified validation to meet the requirement of current good manufacturing practices [1]. The availability of new excipients, newer grades of existing excipients and advanced mechanized technology such as positive die feeding and precompression stages has led to a perceptible shift of direct compression process towards the tablet manufacturing technology. Several directly compressible vehicles (DCVs) with free flow and better compaction properties have been developed in recent years [1–7] and still many others are under development for better performance. As a result, many excipients have been introduced for the last five decades to the pharmaceutical market as filler-binders for tablets, prepared by direct compression. Starches and their derivatives from several natural resources are
⁎ Corresponding author. Tel.: +91 9810720387. E-mail address: [email protected] (F.J. Ahmad). 0032-5910/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.powtec.2012.03.004
extensively investigated for their well known and safety application in formulation development of tablets for various purposes. On answering to this investigation towards several natural starches, rice starch have proved to be much better compaction properties as compared to potato, maize and tapioca starches for the manufacturing of tablets [8]. Assam Bora rice, locally known as Bora Chaval is widely distributed throughout upper Assam in North East region of India, characterized by its high amylopectin contents, and was first introduced in Assam from Thailand or Myanmar by Thai-Ahoms [9–13]. The potential use of Assam Bora rice starch in the formulation of matrix tablet and compression coated tablet for colon targeting has been previously reported by Ahmad and co-workers [10,11]. The current study focuses upon the performance and tableting properties of Assam Bora rice starch as a directly compressible vehicle in contrast to commercially available direct compression excipient, Starch 1500 ®.
2. Material and methods 2.1. Materials Assam Bora rice was procured from the local villagers of Dibrugarh district of upper Assam. Starch 1500 ® was kindly supplied by Anshul Agencies, Mumbai as a gift sample. All other chemicals were of analytical reagent grades.
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2.2. Methods 2.2.1. Isolation of starch from Assam Bora rice Starch was isolated from Assam Bora rice variety Aghuni Bora as per the process described by Ahmad et al. with slight modification [11–14]. About one part of broken rice (fruits of Oryza sativa, family Gramineae) was steeped in two parts of 0.01 M sodium hydroxide solution. The mass was stirred every 1 h and liquor changed every 2 to 3 h. The process was completed, when rice grain was crushable between the fingers. This treatment loosens and partially dissolves the glutinous matter, which holds the starch together. The steeped rice was milled in a mixer grinder with two parts of double distilled water to each part of steeped rice to get milky fluid; it was then diluted with distilled water until it contained about 2–3% of solid. Resulting starch suspension was passed through series of sieves # 20, #44, #80, and #120 respectively. The thick starch suspension was allowed to settle in a 1000 ml beaker. It was then repeatedly washed with 0.0125 M NaOH until the supernatant solution was clear and finally washed with freshly prepared double distilled water to remove the alkali completely. The starch was then concentrated by using a rotary evaporator and dried slowly in hot air oven at 40 °C for 36 h. It was then passed through sieves # 80 and stored in tightly closed container. Isolated starch was characterized by their particle size distribution, flow properties and compressibility analysis. 2.2.2. Particle size and size distribution The size distribution and shapes of the starch were determined by optical microscopy. On approximately 500 starch particles were picked randomly in the optical field of starch powders, from which values of mean projected diameter (dp) were calculated. Heywood diameter (de) was determined using an image processor (Image Hyper 700 II; Japan), by calculating the diameter of circle whose area was equivalent to the actual projected area A of a particle, as shown by Eq. (1) [15]
Diameter de
! rffiffiffi 4 AreaðAÞ π
ð1Þ
Geometric mean diameters (dg) were determined from the lognormal distribution plot of particles mean diameter versus cumulative percent frequency [16,17]. Surface areas of the particles were determined by Quantasorb surface area analyzer (Model QS-7). Helium gas was used as carrier and diluent gas, while nitrogen gas was used as adsorbate. Studies were conducted at relative pressure (P/Po) ranging from 0.05 to 0.30 and specific surface areas (SSABET) were obtained by BET equation [16]. 2.2.3. Powder properties The flow properties of the samples were investigated by the angle of repose, bulk density, and tapped density measurements [16]. The angle of repose was determined on 50 g of sample using a Borosilicate glass funnel (with an orifice diameter and a base diameter of 6.5 mm and 8 cm, respectively). Bulk and tapped densities were measured in 100 ml of a graduated cylinder. The sample contained in the cylinder was tapped mechanically by means of Auto-Tap Shaker (Quantachrome Instruments, USA). The tapped volume was noted down when it showed no change in its value. The data generated from bulk densities and tapped densities were used in computing the Carr's compressibility index and Hausner's ratio for the starches [16]. True density was obtained on a helium pycnometer (Ultrapyc 1200e Helium Pycnometer, Quantachrome Instruments, USA). The data generated from bulk density and true density were utilized for calculating the porosity of powder mass. Moisture content was determined by official method of USP32-NF27 in a mechanical convection oven (Remi Scientific, Bangalore) at 105 °C to the weight constants.
2.2.4. Preparation of tablets 500 mg of each powder (Assam Bora rice starch and Starch 1500 ®) was directly compressed by using 12 mm diameter flat-faced lubricated punch and die set installed in 16 station Cadmach tablet machine (Cadmach, Ahmadabad, India). Tablets were prepared under conditions where maximum compression pressure P ranged from 10 to 250 MPa and the rate of compression was kept constant at 0.03 cm/s. The compression pressure was released immediately after the pressure reached P. After ejection, the tablets were stored over silica gel for 48 h to allow elastic recovery and hardening and to prevent falsely low yield values [18]. 2.2.5. Compactibility analysis After 48 h, final thickness (Tt) and diameter (Dt) of the normal tablet and the tablets with hole (To, Do) were measured and the results obtained was used to determine tablet tensile strength (T) by diametric compression test (TBH30, Erweka, Heusenstamm, Germany) and by applying Eq. (2) [15] T¼
2H πDt Tt
ð2Þ
H = applied load needed to cause the fracture. Results were taken only from those tablets which showed no sign of lamination or capping and split cleanly into two halves. Packing fraction of the tablets (Pt) was obtained by applying Eq. (3) [15] Pt ¼
ρr ρs
ð3Þ
ρr is relative density of the tablets and ρs is true density of powders respectively. ρr was calculated by using Eq. (4) [15]. ρr ¼
Wt ðDt =2Þ2 πTt
ð4Þ
Wt = weight of the tablets. The results obtained from tensile strength versus the product of the solid fraction and the compression pressure was fitted according to the Leuenberger model [19,20] in Eq. (5) ð−γ Pρr Þ T ¼ TMax 1−e c
ð5Þ
Tmax is the theoretical tensile strength at infinite compression pressure; γc is the compression susceptibility parameter (MPa − 1). Data fitting was performed employing the Statgraphic® software (Stat Point Technologies). 2.2.6. Brittle fracture index, Young modulus and toughness 500 mg of each powder was directly compressed into the tablets with hole of 1.5 mm diameter at their center by using an upper punch with a hole through the center and a lower punch fitted with pin (12 mm diameter). After ejection, the tablets were stored over silica gel for 48 h and the resulting stress–strain curves were obtained on a universal stress–strain analyzer ( Q-test-I ®, Material testing system NC, USA). The Young's modulus was obtained from the slope of the stress–strain curves. It measures the stiffness of the material. The toughness of the material was obtained by measuring the area under curves of the resulting stress–strain curves. The brittle fracture index (BFI) was calculated from Eq. (6) [21] BFI ¼ 0:5
T −1 To
ð6Þ
where T is the tensile strength of normal tablet and To is the tensile strength of the tablet with hole.
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2.2.7. Lubricant sensitivity Lubricant sensitivity analysis was performed by the method described by Rojas et al. [19] with slight modification. Starch powders and magnesium stearate (1% w/w) were mixed using a double cone blender for 5 to 60 min. After mixing, the powder mass was passed through ASTM (American Society of Testing and Materials) 80 mesh sieves. Tablets of 500 mg were compressed at 75 Mpa compression pressure. In the similar fashion another batch of tablets were prepared without lubricants. Lubricant sensitivity (LS) was determined by Eq. (7) LS ¼
Fo −Flub Fo
ð7Þ
Flub and F0 are the hardness of the tablets prepared with and without lubricants. Hardness test was performed on the hardness tester (TBH30, Erweka, Heusenstamm, Germany). 2.2.8. Compressibility analysis The Kawakita equation is used to study the powder compression using the degree of volume reduction (C) and is written as [22] Vo −Vp ¼ abP=ð1 þ bPÞ Vo
C¼
and ρa can be calculated from Eq. (13) ð8aÞ A ¼ ln
or F F 1 ¼ þ C a ab
ð8bÞ
In the foregoing equation, V0 denotes the initial volume of powder bed and VP is the powder volume after compression. The terms a and b are constants, a is equal to minimum porosity of the material before compression representing the compressibility index and is related to the total volume reduction for the powder bed, while b represents the plasticity of material and is related to the resistant forces (Friction/ Cohesion) to compression [19] Compression behavior of powders was characterized by Heckel plots [23] by using Eq. (9) ln
1 1−ρr
¼ KP þ A; ε ¼ 1−ρr
ð9Þ
where ρr is the relative density of the compact at pressure P, ε is the porosity of powders, and K and A are constants. It represents the powder densification by die filling and particle rearrangement before deformation and bonding of discrete particles take place. The slope of the straight line, K is reciprocal of the mean yield force, PY of the material. ε is the porosity of powder bed. Densification of a powder by die filling is expressed by Eq. (10) [23–25]. ln
1 1−ρo
ð11Þ
Here B describes the volume reduction by particle rearrangement. Relative densities corresponding to the processes above are ρa, which includes both die filling and particle rearrangement and ρb, which describe the extent of particle rearrangement. The relative densities can be related by Eq. (12) ρ a ¼ ρo þ ρb
1 1−ρa
ð13Þ
2.2.9. Statistical analysis The student t test was used to find the statistical significance. A value of P b 0.05 was considered statistically significant. All tests were performed in the replicate of 10 independent samples. 3. Results 3.1. Particle size and size distribution The size distribution of the Assam Bora rice starch and Starch 1500 ® was 25–120 μm and 30–150 μm respectively (Fig. 1). The results of physical and geometric properties of the starches are presented in Table 1. The projected diameter of the Assam Bora rice starch is 12 ± 1.320 μm, whereas for Starch 1500 ® this value is 9 ± 1.061 μm. The result was found to be statistically significant (P b 0.001). 3.2. Powder properties The flow properties of the samples were investigated by the angle of repose, bulk density, and tapped density measurements, Carr's compressibility index, Hausner's ratio and porosity, are summarized in Table 1. The result was found to be statistically significant (P b 0.001).
ð10Þ
where ρo is the relative density of a powder and usually derived from the bulk density. The combined effect of die filling and particle rearrangement at low pressure can be described by Eq. (11) 1 A ¼ ln þB 1−ρo
Fig. 1. Particle size distribution of Assam Bora rice starch and Starch 1500® (n = 500).
ð12Þ
Table 1 Powder characteristics and flow properties of Assam Bora rice starch and Starch 1500®. Properties
Assam Bora rice starch
Starch 1500®
dp (μm) de ((μm) dg (μm) SSABET (m2/g) Angle of repose (degree) Compressibility index (%CI) Hausner's ratio (H) Bulk density (ρb) Tapped density (ρt) True density (ρp) % Porosity (ε) %Moisture content
12 ± 1.320 15.67 ± 0.46 58.7 ± 2.050 10.5 ± 0.670 23.02 ± 1.01 15.92 ± 1.23 1.18 ± 0.001 0.586 ± 0.01 0.697 ± 0.03 1.57 ± 0.23 62.67 ± 2.34 4.31 ± 0.78
9 ± 1.061 13.12 ± 0.02 69.9 ± 5.09 6.8 ± 1.43 27.09 ± 0.08 17.16 ± .045 1.20 ± 0.002 0.579 ± 0.001 0.689 ± 0.002 1.53 ± 0.067 63.15 ± 4.67 9.87 ± 1.09
All values are expressed as mean ± s.d., n = 10.
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Table 2 Results obtained from compactibility analysis, brittle fracture index, young modulus and toughness. Sample
AUCT (MPa2)⁎
Tmax (Mpa)⁎
γc (Mpa- 1)
BFI⁎
Young modulus⁎
Maximum stress (MPa)⁎
Maximum strain (%)⁎
Toughness (MPa)⁎
Lubricant sensitivity⁎
Assam Bora rice starch Starch 1500®
2438.7 ± 50.32 1663.4 ± 25.56
43.98 ± 2.54 21.78 ± 3.56
0.004 0.006
0.962 ± 0.006 1.234 ± 0.034
0.31 ± 0.005 0.26 ± 0.001
5.13 ± 0.236 3.73 ± 0.372
1.89 ± 0.31 1.67 ± 0.03
892 ± 19.09 786 ± 13.67
0.31 ± 0.01 0.53 ± 0.03
⁎All values are expressed as mean ± s.d, n = 10.
Fig. 2. Tensile strength of compact prepared from Assam Bora rice starch and Starch 1500® at different compression pressures.
3.3. Compactibility analysis The results from Leuenberger model for tensile strength are presented in Table 2. The compactibility expressed as the area under the tensile strength (AUCT) of Assam Bora rice starch was about 1.5 times greater than that of Starch 1500 ®. Tmax for the Assam Bora rice starch is higher than Starch 1500 ®. The compression susceptibility value for Assam Bora rice starch is smaller than Starch 1500 ®. Effect of compression pressure on the tensile strength of compact is presented in Fig. 2. 3.4. Brittle fracture index, Young modulus and toughness BFI obtained from Eq. (6) is presented in Table 2. The lowest BFI was observed for Assam Bora rice starch (0.962 ± 0.006) than Starch 1500 ® (1.234 ± 0.034). The value of Young's modulus for Assam Bora rice starch and Starch 1500® varies from 0.31 ± 0.005 to 0.26 ± 0.001 respectively. The toughness of the materials was obtained by measuring the area under curves of the resulting stress–strain curves. Toughness value for the tablet from Assam Bora rice starch and Starch 1500® varies from 892 ± 19.09 to 786 ± 13.67 Mpa respectively.
for the Assam Bora rice starch and Starch 1500 ® varies from 0.63 to 0.58 respectively. The “b” parameter obtained from Kawakita analysis is lower for the Assam Bora rice starch. The value of yield pressure (Py) of Assam Bora rice starch is comparable to Starch 1500®.
4. Discussion 4.1. Particle size and size distribution Particle size and surface area always play a vital role for the release of drug from its dosage form. Greater surface area brings about intimate contact of the drug with dissolution fluid in-vivo and enhances the drug solubility and dissolution. Assam Bora rice starch shows uniform particle size distribution. The specific surface area is used to describe the area of contact between the particles. The specific surface area obtained by the BET analysis showed that Assam Bora rice starch had larger surface areas than Starch 1500®. The larger the specific surface area and smaller is the particle size, the larger the area of contact between the particles. This observation is true for Assam Bora rice starch.
3.5. Lubricant sensitivity Lubricant sensitivity was tested against Magnesium stearate at 1% w/w level. The trend for lubricant sensitivity was observed as Starch 1500 ® > Assam Bora rice starch. Lubricant sensitivity and blending time of the Assam Bora rice starch and Starch 1500 ® are presented in Figs. 3 and 4 respectively. 3.6. Compressibility analysis Table 3 shows the parameters resulting from the different compression models employed. The compressibility index i.e. “a” for the Assam Bora rice starch is close to the values of its porosity. The value of “a”
Fig. 3. Lubricant sensitivity of Assam Bora rice starch and Starch 1500®.
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Fig. 4. Effect of blending time and lubricant sensitivity of Assam Bora rice starch and Starch 1500®.
4.2. Powder properties Angle of repose, compressibility index and Hausner's ratio collectively constitute the simple, fast and popular mean of predicting flow properties, were chosen for flow characterization. Corresponding values indicate good flow property (USP34-NF29). It may be due to its high densification, more regular morphology and reduced porosity. Assam Bora rice starch presented higher bulk and tap densities than Starch 1500 ®. This phenomenon is due to its lower particle size and higher consolidation achieved during process. Thus, Assam Bora rice starch exhibits a more regular, smooth and almost spherical particles, which were more compactable than Starch 1500 ®. Porosity of Assam Bora rice starch and Starch 1500® varies from 62.67 ± 2.34 to 63.15 ± 4.67 respectively. In this case, regular, smooth and almost spherical shape of the Assam Bora rice starch made packing more convenient and hence its porosity was reduced. Moisture content of Assam Bora rice starch is significantly less as compared Starch 1500®. This is due to fact that pregelatinized starch i.e. Starch 1500® is hygroscopic. 4.3. Compactibility analysis The compression susceptibility (γc) was lower for Assam Bora rice starch than Starch 1500 ®. Further compactibility expressed as the area under the tensile strength of Assam Bora rice starch and Starch 1500 ® varies from 2438.7 ± 50.32 to 1663.4 ± 25.56 respectively. The predicted maximum tensile strength value (Tmax) for the Assam Bora rice starch is about two fold greater than that of Starch 1500 ®, thus better compactibility than Starch 1500 ®. 4.4. Brittle fracture index, Young modulus and toughness The brittle fracture index is a measure of the ability of a tablet to relieve stress that is caused by the presence of defective region (hole) [19]. Since a low value of BFI is desirable for minimizing the lamination and capping of tablet, therefore, in this regard Assam Bora rice starch would be more useful. Young's modulus measures the stiffness of the material i.e. the resistant of the material to elastic deformation when it is compressed. Assam Bora rice starch had a higher Young modulus than Starch 1500®, indicating a high resistance to elastic deformation. Table 3 Parameter derived from Kawakita and Heckel analyses of Assam Bora rice starch and Starch 1500®. Sample
Assam Bora rice starch Starch 1500®
Kawakita parameters
Heckel parameters
a
B
Py
ρa
ρb
ρo
0.63 0.58
0.14 0.20
81 78
0.61 0.59
0.58 0.57
0.15 0.18
The toughness of the material represents the resistance when compressed until breaking [19,26]. Tablets prepared from Assam Bora rice starch can withstand a minimum of 6 Mpa compression force before breaking, while the value for the tablets prepared from Starch 1500® was 2.5 Mpa. The large toughness value indicates the increased ability of Assam Bora rice starch to absorb and withstand applied force. 4.5. Lubricant sensitivity Magnesium stearate is commonly used in tablet formulations to reduce friction between the material and tooling used. Starch 1500 ® is known for having high sensitivity to lubricants [27]. These results suggest that materials with low Py value are more sensitive to magnesium stearate, and thus sensitivity decreases as the ductility of the material decreases. As seen in Fig. 3, the trend for lubricant sensitivity ranged as: Starch 1500 ® > Assam Bora rice starch. Fig. 4 shows the relationship between blending time and lubricant sensitivity. In case of Assam Bora rice starch, a plateau in sensitivity is achieved within 25–30 minutes of blending. This suggest that covering effect of Magnesium Stearate reaches a limit between 25and 30 min and new available sites for particle binding are formed afterwards. Long mixing time with lubricant had a major effect on the lubricant sensitivity of Starch 1500 ®. 4.6. Compressibility analysis To clarify the change in the tableting properties of the Assam Bora rice starch and Starch 1500 ®, the compression behavior was analyzed by developing the Kawakita equation and Heckel analysis. Kawakita analysis showed comparable total compressibility “a” values from Assam Bora rice starch and Starch 1500 ®. Furthermore “b” parameter showed that Assam Bora rice starch is the material with lowest cohesive forces to compression. Thus compressibility range follow the order Assam Bora rice starch > Starch 1500 ®. Since Assam Bora rice starch has the high volume reduction, it also had highest compactibility and theoretical tensile strength. Yield pressure (Py) of the Assam Bora rice starch and Starch 1500 ® are comparable indicating a similar onset of Plastic deformation under compression. Since in both sample ρb is larger than ρo, thus densification through particle rearrangement was more widespread than die filling at lower compression pressures. 5. Conclusion This study demonstrated the promising use of Assam Bora rice starch as direct compression agent/excipients. Assam Bora rice starch exhibited good flow properties. Results connote that Assam Bora rice starch would be more useful in minimizing the problems of lamination and capping especially on high speed tableting machine with short dwell time for the plastic deformation of material while on the other hand,
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Fig. 5. Tablet prepared from Assam Bora rice starch by direct compression.
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