The disintegrant potential of native starches of five new cassava (
Starch and its derivatives (native starches and modified starches, e.g., sodium starch glycolate) are principally used as disintegrants in pharmaceutical tablet formulations. Starch and its derivatives are also used as diluents, binding agents, glidants, and thickeners. Disintegrants are pharmaceutical excipients that are included in tablet formulations with the aim of facilitating the break-up of the compressed tablets into small fragments in aqueous media. The enhanced splitting of the tablets in aqueous media enhances the dissolution, absorption, and bioavailability of orally administered drugs. Other substances employed as disintegrants in pharmaceutical formulations are cellulose and its derivatives (e.g., microcrystalline cellulose, croscarmellose sodium, and low-substituted hydroxypropyl cellulose), resin and its derivatives, and crospovidone [
Native starches derived from botanical sources are commonly employed as disintegrants in pharmaceutical tablet formulations usually in a concentration range of 2–10% w/w [
Various mechanisms of disintegration have been proposed for disintegrants. These mechanisms which have variable application to different types of disintegrants are swelling, capillary action or wicking, strain recovery, heat of interaction, and interruption of particle-particle bonds [
The first disintegrating agents to be used in tablet formulations were native starches of maize, potato, and wheat [
The Crop Research Institute of Ghana (CRIG), Fumesua, is using genetic techniques to develop new cassava varieties with high starch, fiber, nutrient content, and other functional properties. The aim of the current study was to evaluate the disintegrant properties of native starches of five improved cassava varieties developed by CRIG, Fumesua, in paracetamol tablet formulations. Paracetamol was used as a model drug because it has poor flow and compression properties and high capping and lamination tendencies and lacks any inherent disintegrant activity. The effects of the cassava starch disintegrants on the physicomechanical and drug release properties of the formulated paracetamol tablets were evaluated.
Five varieties of matured fresh root tubers of cassava (
Freshly harvested cassava tubers were washed, peeled, cut into small pieces, rewashed, and weighed. The cassava was milled into a pulpy slurry, passed through a nylon fiber, and left to stand for 12 h after which the supernatant was decanted. The cassava starch was collected, dried at 40°C for 30 min in an oven, reduced to fine powder by trituration, and passed through a 1.6 mm sieve. The percentage starch yield was calculated as follows:
Ten grams of cassava starch powder was weighed and added to 15 ml distilled water and mixed. Boiling distilled water was added to the mixture to make up to 100 ml. The slurry was allowed to cool and the pH was determined with a Eutech pH meter (pH 510, pH/mV/°C meter, Singapore). The total ash, acid insoluble ash, and water soluble ash of the cassava starches were determined using official methods [
The tapped volume occupied by 10 g of the powdered cassava starch in a 100 ml measuring cylinder was recorded (
The solubility of the cassava starch powders was determined in cold water, warm water, chloroform, and ethanol (96%) at 25°C. Five hundred milligrams of the starch powder was added to 50 ml of solvent and allowed to stand overnight. Twenty-five milliliters of the supernatant was placed in preweighed Petri dishes and evaporated to dryness over a water bath and further dried to constant weight in an oven at 100°C. The mass of the residues was determined with an analytical balance (Adam equipment, UK) and expressed as the percent solubility of the cassava starch in the respective solvents.
Thirty grams (
A funnel was clamped with its tip 2 cm above a hard horizontal surface. The starch powder was allowed to flow through the funnel until the apex of the powder formed just touched the funnel’s tip. The height (
The content of the toxic metal ions of cadmium (Cd), arsenic (As), lead (Pb), and mercury (Hg) in the cassava starches was determined with an atomic absorption spectrophotometer (Buck Scientific Model 210V GP) as previously reported [
A Fourier transform infrared spectrometer (FTIR) (PerkinElmer, UATR Spectrum 2, 941333, UK) was used to determine the compatibility between paracetamol and the cassava starches. The spectra of the individual starches, paracetamol, and the physical mixtures of the drug and starch were recorded by scanning in the wavelength region 4000–400 cm−1 using the FTIR spectrometer by placing the sample into a diffuse reflectance sampler. The spectra of the three samples were superimposed to assess whether or not the principal absorption bands present in the drug and starches are present in the physical mixtures.
Paracetamol granules (420 g) comprising of paracetamol (83.3%) as active pharmaceutical ingredient, lactose (0.2, 2.7, 5.2%) as diluent, polyvinylpyrrolidone, PVP (4.5%), as binder, talc (1.2%) as glidant, magnesium stearate (0.2%) as lubricant, and cassava starch or maize starch BP (5, 7.5, 10%) as disintegrant were prepared by the wet granulation method. The required amount of paracetamol was dry-mixed with lactose and starch and moistened with PVP solution and massed for 10 min in a V-blender (Cadmach Machinery Co. Pvt. Ltd., India). The damp mass was manually screened through a number 12 mesh sieve (1680
The uniformity of weight of twenty randomly selected tablets from each batch was determined according to the British Pharmacopoeia method [
The thickness and diameter of ten randomly selected tablets from each batch were determined using a digital vernier caliper (4Cr13 stainless steel digital caliper, China).
The paracetamol content of the tablets produced was determined using the procedure described in the British Pharmacopoeia [
The crushing strength
The friability of the tablets was determined with an Erweka Friabilator (TA 20, GmbH, Heusenstamm, Germany). Ten tablets weighing ~6.0 g from each batch were placed in the friabilator and it was operated for 4 min at 100 rpm. The tablets were dedusted and reweighed and the difference in tablet weight was determined. The friability was calculated as follows:
The disintegration time of the tablets of each batch was determined using an Erweka disintegration apparatus (ZT-4, Erweka, Heusenstamm, Germany) as described in the British Pharmacopoeia [
The disintegration efficiency ratio (DER) was determined using the relationship
In vitro tablet dissolution tests were undertaken with an Erweka dissolution apparatus (Type DT6, GmbH, Heusenstamm, Germany) under sink conditions. Dissolution was determined in 900 ml phosphate buffer pH 5.8 at a paddle speed of 50 rpm and temperature of
Differences among mean values were determined using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc multiple comparison test with GraphPad Prism version 5.00 for Windows (GraphPad Software, San Diego California, USA). At 95% confidence interval,
All the five varieties of cassava (
Some physicochemical properties of starches extracted from the five varieties of cassava.
Parameter | Type of cassava starch | ||||
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V10 | V20 | V30 | V40 | V50 | |
Starch yield (%) | |
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Moisture content (%) |
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Ph |
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Swelling index (%) |
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Ash values | |||||
Total ash (%) |
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WSA (%) |
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AIA (%) |
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Solubility (mg/ml) | |||||
Cold water |
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Warm water |
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Ethanol |
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Chloroform |
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Bulk properties (g/cm3) | |||||
Particle density |
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Fluff density |
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Tapped density |
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Flow properties | |||||
Hausner ratio |
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Carr’s index (%) |
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Angle of repose (°) |
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Particle diameter ( |
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Toxic metals (mg/100 g) | |||||
Cadmium | 1.650 |
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Arsenic | 0.013 |
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Lead | 0.010 |
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0.000 |
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0.000 |
(a)
The bulk properties describe the density, consolidation, and flow of a powder mass. It also denotes how well the starch powders can be compressed since smaller particle sizes resist free flow because of adhesion between the powders [
The cassava starches had poor solubility in cold water, 96% ethanol, and chloroform. There was, however, marked increase in the solubility of the cassava starches in warm water. The swelling power of starches is employed to predict the swelling of tablets during disintegration test in order to release the drug for dissolution [
Carr’s index and Hausner ratio both describe the compressibility of the starch powder while the angle of repose characterizes the flow properties of powders and is dependent on the interparticulate resistance to movement between particles [
The toxic metal ion analysis showed the absence of mercury and an insignificant amount of the toxic heavy metals of arsenic, lead, and cadmium. This suggests the possible nontoxicity of the cassava starches and could therefore be used as pharmaceutical excipients. The total ash, water-insoluble ash, and acid insoluble ash values of the cassava starches were low which suggests that the amounts of earthly materials or adulterants present in the cassava starches are insignificant. The physicochemical properties investigated are important in determining the functional properties of the cassava starches.
Figure
FTIR spectra of pure paracetamol (active), cassava starch (V30), and the physical mixture of paracetamol and cassava starch (V30 active).
Paracetamol tablets containing different concentrations of the cassava starches as disintegrants were produced by the wet granulation technique. The starch disintegrants were added to the tablet formulations intragranularly. Table
Some physical properties of paracetamol tablets produced using different concentrations of the cassava starch disintegrants.
Type of cassava starch | Starch concentration (% w/w) | Tablet weight (g) |
Tablet thickness (mm) |
Tablet diameter (mm) |
Drug content (%) |
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V10 | 5.0 |
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7.5 |
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10.0 |
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V20 | 5.0 |
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7.5 |
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10.0 |
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V30 | 5.0 |
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7.5 |
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10.0 |
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V40 | 5.0 |
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7.5 |
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10.0 |
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V50 | 5.0 |
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7.5 |
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10.0 |
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5.0 |
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7.5 |
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10.0 |
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(a)
Tablets should have strong tensile strength to withstand pressure due to handling, film-coating, and packaging but must be weak enough to allow drug release after administration. In general, the tensile strength of the tablets reduced with increase in cassava starch concentration. There were no significant differences (
The crushing strength-friability ratio (
Tensile strength (
Type of cassava |
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V10 | 5.0 | 75.8 | 63.2 | 0.74 | 12.58 | 6.79 | 0.45 |
7.5 | 74.6 | 55.7 | 0.90 | 13.10 | 4.72 | 0.35 | |
10.0 | 82.6 | 66.0 | ND | 3.20 | — | — | |
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V20 | 5.0 | 91.2 | 77.4 | 0.88 | 14.00 | 6.28 | 0.42 |
7.5 | 112.4 | 97.4 | 0.46 | 12.00 | 17.64 | 1.32 | |
10.0 | 67.7 | 50.7 | 0.43 | 5.00 | 23.58 | 2.49 | |
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V30 | 5.0 | 96.4 | 74.3 | 0.92 | 14.10 | 5.73 | 0.38 |
7.5 | 78.0 | 65.8 | 0.89 | 13.06 | 5.66 | 0.42 | |
10.0 | 73.1 | 61.3 | 0.71 | 9.10 | 9.49 | 1.00 | |
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V40 | 5.0 | 87.2 | 76.1 | 0.28 | 13.40 | 20.28 | 1.35 |
7.5 | 94.7 | 94.3 | 0.71 | 10.00 | 13.28 | 0.99 | |
10.0 | 69.8 | 55.7 | 0.27 | 4.45 | 46.36 | 4.90 | |
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V50 | 5.0 | 117.6 | 98.4 | 0.29 | 14.30 | 23.73 | 1.58 |
7.5 | 84.4 | 69.7 | 0.91 | 11.36 | 6.74 | 0.50 | |
10.0 | 82.6 | 62.8 | 0.43 | 7.55 | 19.34 | 2.04 | |
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5.0 | 126.0 | 96.1 | 0.45 | 14.20 | 15.04 | — |
7.5 | 102.5 | 79.0 | 0.45 | 13.15 | 13.35 | — | |
10.0 | 87.7 | 64.0 | 0.59 | 11.46 | 9.46 | — |
(a) ND: not determined due to the break-up of the tablets; (b)
The dissolution profiles of the paracetamol tablets containing different concentrations of the cassava starches in phosphate buffer pH 5.8 are shown in Figure
Dissolution profiles of paracetamol tablets containing (a) 5% w/w cassava starch, (b) 7.5% w/w cassava starch, and (c) 10% w/w cassava starch in phosphate buffer pH 5.8 (mean ± SD,
The results showed that the five cassava varieties have low starch yields. The starches contained negligible amounts of toxic metal ions and generally exhibited good physicochemical properties required for use as pharmaceutical excipients. The five cassava starches employed as intragranular disintegrants in concentrations of 5–10% w/w produced paracetamol tablets with satisfactory physical properties comparable with maize starch BP. There were no interactions between the starches and the active pharmaceutical ingredient and excipients used in producing the tablets. Generally, the tensile strength (
The authors declare that there are no conflicts of interest regarding the publication of this paper
The authors gratefully acknowledge the technical assistance provided by the technical staff of the Central Laboratory and the Department of Pharmaceutics, both of the Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.