Formulation and Characterization of Moringa oleifera Leaf Granules. I: Micromeritic Properties.

 

Ebere I. Okoye^1*, Titilope O. Awotunde², Tessy G. Morales²

¹Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Benin,

Benin City, Edo State, Nigeria.

²Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmacy, Madonna University,

Elele, Rivers State, Nigeria.

 

ABSTRACT:

Micromeritic properties of pharmaceutical powders are among the primary parameters given serious consideration prior to their formulation into various solid drug delivery systems. To study these, granules of M. oleifera leaf powder were formulated via wet granulation using gelatin (G), polyvinylpyrrolidone (P), and corn starch BP (CS) as binders at various concentrations (1.0 – 5.0% w/w for  G and P; 5.0 - 10.0% w/w for CS), and CS at 10.0% w/w and 12.5% w/w as disintegrant. The resulting granules and the ungranulated leaf powder were characterized by studying their particle sizes, particle densities, particle size distributions, flow rates, angles of repose, Hausner’s ratios, Carr’s indices, porosities and bulkiness using standard protocols. Results revealed that, the mean particle diameter for the non-granulated leave powder (MOP) was 192 µm, while those of the granules ranged between 194 µm and 275 µm. The particle densities were of values between 1.12 g/ml and 1.36 g/ml with significant difference between them (p < 0.05); while the flow indices were lowest for MOP. Among the granulated products, granules formulated with gelatin 1% w/w as binder and cornstarch BP 10% w/w as disintegrant displayed the least porosity and bulkiness which translates to the best packability and most economical for production and transportation of the finished product. Based on this study, these excipients are suggested to be given choice consideration in the formulation of M. oleifera granules with acceptable micromeritic properties. 

 

 

INTRODUCTION:

Moringa oleifera Lam. family Moringaceae, commonly referred to as horse - radish tree, drumstick tree or mother’s best friend, is a small fast-growing ornamental tree whose origin has been traced to India. The plant is a deciduous tree that usually grows up to 10 or 12 m in height. Different parts of the plant are consumed as food in many cultures and the nutritional contents of the plant have been reported^{1, 2}. The root, bark, pods and leaves of this tree are used in traditional medicine for the treatment of various human ailments such as headaches, worms, diarrhoea, stomach ulcers, skin conditions, anaemia, infections, fevers, urinary problems, liver and spleen problems, diabetes, hypertension, malignancy, arthritis and rheumatism^2-9.

 

Various parts of this plant have therefore been presented in different dosage forms (external and oral) for the treatment or management of both human and veterinary ailments^{10, 11, 12}. However, the presentations of most of these dosage forms may not enable easy scale up processes in the pharmaceutical industries and this entails obvious disadvantages for large scale production of this miracle product. All Moringa oleifera leaf dosage forms, except one (from Genius Nature Herbs Private Ltd)¹³ are presented as bulk powders or divided powers in capsules that are manually filled¹⁴.

 

Granulation may be defined as a size enlargement process which converts fine or coarse particles into physically stronger and larger agglomerates having good flow property, better compression characteristics and uniformity. There are many other reasons for granulation such as: increasing the bulk density of a product; facilitating metering or volumetric dispensing; controlling the rate of drug release; decreasing dust generation thereby reducing employee exposure to drug product; improving product appearance¹⁵. Granulation of powders improves their compressibility and compactibility, promotes a better handling as a consequence of a higher control over the product’s bulk density (even for high drug contents), narrows the size distribution of the particles produced and provides a better control of the drug’s content uniformity at low drug concentrations^{16, 17}.

 

The science and technology of small particles was given the name Micromeritics by Dalla Valle (1948)¹⁸. Information describing materials characterization, particle size, surface properties, porosity, and pore structure is essential to a great many technologies and industries. The potential for applications of these characterization techniques, derived from an immeasurable diversity of materials and their uses, may itself be unlimited. In the area of tablet and capsule manufacture, control of particle size is essential in achieving the necessary flow properties and proper mixing of granules and powders¹⁸. Excipients influence the micromeritics of herbal as well as synthetic active pharmaceutical ingredient powder mixtures or granules in diverse ways. In wet and dry granulation processes, binder type and concentration influence the micromeritic properties of granules and therefore the quality of tablets or capsules produced with the granules. In tablet production, press speed requires powders to be very fluid, a property commonly referred to as product flowability. Good flow characteristics are necessary because the mechanical action of the tablet press requires a volume of fill. The volume of fill represents the actual tablet weight. A tablet press does not weigh the precise amount of powder for each tablet. To achieve consistent tablet weights, the formula must be designed to flow consistently and to fill volumetrically. The powders in a formula must therefore possess a consistent particle-size distribution and density to attain proper flow and achieve volume of fill (i.e., tablet weight). In other words, the powders must flow consistently to attain consistent results¹⁷. Furthermore, in automated capsule filling processes, excellent flow properties are primary to ensuring uniformity of dose since the principle of volume of fill is also applicable. These requirements inform the current study to investigate the best binder and disintegrant combination for the formulation of Moringa oleifera granules whose qualities meet compendial standards.

 

MATERIALS AND METHODS:

Moringa oleifera leaves were collected in Oyo, Oyo State, Nigeria. The leaves were authenticated by Dr (Miss) R.A. Lawal of Lagos State University, Lagos. Excipients used included corn starch BP (Sigma – Aldrich, USA) – as binder and disintegrant, polyvinylpyrrolidone (PVP K15) (Fluka, USA) – binder, gelatin [gel strength (Bloom): 160] (Fluka Germany) – binder, xylene of specific gravity, 0.879 g/ml (Sigma – Aldrich, Germany). Other reagents are of analytical grade.

 

Preparation of Moringa oleifera leaves powder

The leaves were shade dried for two weeks in the month of March, and then pulverised using a blender. Thereafter, the powder was divided into two: the one for granulation was passed through sieve of aperture size 150 µm while the remainder was sieved using sieve of aperture size 600 µm. The resulting powders were stored in air tight containers.

 

Determination of average moisture loss on drying

The method described in BP 2009¹⁹, was adopted with slight modification. One gram of the Moringa oleifera leave powder was weighed in tarred petri dish. The petri dish with its content was placed in an oven (Lab. Oven Model No. DHG –9101. 1SA, Ceword Medical Equipment, England) and dried at 105^oC for 3 h. Thereafter, the petri dish with content was cooled in a desiccator over anhydrous silica gel and reweighed.  The moisture content was then determined as the ratio of weight of moisture loss to weight of sample expressed as a percentage. Triplicate determinations were made and the means of the values reported.

 

Preparation of granules

Eighteen (18) batches of a basic formulation of Moringa oleifera leaf powder (15 g), and corn starch BP. as disintegrant (10.0% or 12.5% w/w with respect to the weight of herbal drug powder and binder where applicable) were dry – mixed for 10 minutes in a planetary mixer (Model A120, Hobart Manufacturing CO, UK), moistened with the appropriate amount of binder solution (gelatin, PVP) or mucilage (corn starch BP) prepared according to the methods reported by previous researchers^{20, 21} except that the volume of the solutions or mucilage was maintained at 7.5 ml) equivalent to 1.0, 3.0, 5.0% w/w (gelatin, PVP) or 5.0, 7.5, 10.0% w/w (corn starch BP) in the final granules. Wet massing was carried out with mortar and pestle for 10 min. The homogeneous wet mass was then screened through a 1400μm sieve and the wet granules dried in a hot air oven (Lab. Oven Model No. DHG –9101. 1SA, Ceword Medical Equipment, England) at 50^oC for 2 h. Thereafter, the dried granules were screened through a 600 μm sieve in order to generate uniformly sized granules²² and stored in air tight containers over silica gel before subsequent tests were conducted on them.

 

Particle size analysis of granules

Each sieve was tarred to the nearest 0.001 g. Thereafter, 10 g of ungranulated Moringa oleifera leaf powder or the granules was carefully loaded on the coarsest sieve of the assembled stack (1000µm to 150µm) and the lid was replaced. The nest was subjected to mechanical vibration using the Shaker (AS 400 Retsch, Germany) for 25min at 5min interval per shaking session. Thereafter, the sieves were carefully separated and each sieve was carefully reweighed with its content. The weights of powder retained on each sieve and the collecting pan were determined by difference. The values were used to calculate the percent of sample retained on each sieve^{23, 24, 25, 26} and the average diameter of the particles (d_av) using the formula²⁷:

 

 

Determination of powder / granule particle density

Xylene was used as the displacement fluid. The pycnometer, very clean and dry, was weighed and its weight recorded. It was filled with xylene, the counterpoise replaced, and the excess fluid carefully and completely wiped off. The bottle with its content was weighed and the weight recorded. The pycnometer was then emptied, washed thoroughly with soapy water, rinsed with acetone, and dried very well in the hot air oven (Lab. Oven Model No. DHG –9101. 1SA, Ceword Medical Equipment, England) at 40^oC. The dry pycnometer was reweighed to check if there was difference between the new dry weight and the initial one. Thereafter, some quantity of leaf powder/granules being examined was introduced very carefully into the dry pycnometer, the counterpoise was replaced and the bottle with its content weighed. The weight of the powder/granules was therefore determined by difference. A little xylene was introduced into the pycnometer and the bottle shaken carefully to displace the air bubbles entrapped by the powder/granule particles. Finally, the bottle was filled with xylene, its counterpoise replaced, and the excess fluid wiped off thoroughly. The bottle with its contents was again weighed and the reading recorded. This procedure was carried out thrice for each batch of powder/granules and the mean value used in calculating the particle density (r_s) using the equation below:

 

 

Where w is powder/granule weight; S_g is the specific gravity of xylene; a is the weight of pycnometer + xylene, and b is the weight of pycnometer + xylene + granules²⁸.

 

Determination of bulk, tapped and relative densities, bulkiness and porosity of powder / granule bed

The bulk density of each powder / granule sample was determined by pouring 10 g (M) of the powder into a 50 ml glass measuring cylinder and the bulk volume (V_o) determined. The bulk density (D_b) was then calculated from the relationship:

 

Triplicate determinations were made and the mean values reported²⁸.

 

The tapped density of each powder was determined using Stampf Volumeter (model STAV 2003, JEF Germany). The ten grams (M) of each powder/granules sample after the bulk density determination was subjected to 250 taps mechanically and the volume V₂₅₀ of the powder column determined and applied to evaluate tapped density (D_t) using the relationship:

 

Triplicate determinations were made and the mean values reported²⁸.

Relative density and porosity of powder / granules bed after 250 taps were determined using the equations 5 and 6 respectively:

 

Where RD = relative density, ρ_{s =} particle density, ε = porosity.

Determination of Angle of repose

The static angle of repose, θ, was measured according to the fixed funnel and free standing cone method. A glass funnel was clamped with its tip of diameter 1 cm at a given height (h = 1.5 cm) above a graph paper placed on a flat surface. Ten gram of powder/granules sample was carefully poured through the funnel until the apex of the cone thus formed just reached the tip of the funnel. The diameter (d) of the base of the cone was measured. This procedure was repeated three times for each powder/granules batch and the means were used to calculate the angle of repose for each powder/granule sample using the formula:

 

Hausner’s ratio (HR)

This was calculated using the formula:

 

Where D_t = Tapped density; D_b = Bulk density

 

Carr’s Index (compressibility Index – CI)

This was calculated using the formula:

 

Statistical analysis

One way ANOVA (Excel 2007) was applied, and p < 0.05 indicated statistically significant difference.

 

RESULTS AND DISCUSSION:

Table 1: Some micromeritic properties of M. oleifera leaf powder and granules

Batch	Mean particle size (µm)	Particle density (g/ml)	Bulk density (g/ml)	Tapped  density (g/ml)
MOP	192	1.12±0.007	0.32	0.45
G1CS10	265	1.28±0.061	0.53	0.68
G3CS10	239	1.29±0.060	0.45	0.58
G5CS10	269	1.29±0.046	0.48	0.58
G1CS12.5	235	1.32±0.069	0.43	0.55
G3CS12.5	228	1.32±0.079	0.42	0.55
G5CS12.5	202	1.33±0.089	0.42	0.55
P1CS10	198	1.16±0.038	0.43	0.53
P3CS10	275	1.29±0.329	0.43	0.53
P5CS10	218	1.14±0.046	0.41	0.53
P1CS12.5	200	1.21±0.138	0.45	0.53
P3CS12.5	245	1.25±0.089	0.33	0.42
P5CS12.5	217	1.31±0.057	0.40	0.53
CS5CS10	255	1.36±0.046	0.36	0.48
CS7.5CS10	261	1.36±0.077	0.34	0.45
CS10CS10	240	1.34±0.033	0.33	0.46
CS5CS12.5	230	1.30±0.055	0.37	0.48
CS7.5CS12.5	232	1.33±0.060	0.36	0.48
CS10CS12.5	194	1.33±0.070	0.38	0.49

MOP- M. oleifera leaf powder; G1CS10, G3CS10, G5CS10- granules containing gelatin 1.0 – 5.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; G1CS12.5, G3CS12.5, G5CS12.5-  granules containing gelatin 1.0 – 5.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively; P1CS10, P3CS10, P5CS10-  granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch  10% w/w  as binder and disintegrant respectively; P1CS12.5, P3CS12.5, P5CS12.5-granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch 12.5% w/w  as binder and disintegrant respectively; CS5CS10, CS7.5CS10, CS10CS10- granules containing corn starch 5.0 – 10.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; CS5CS12.5, CS7.5CS12.5, CS10CS12.5-  granules containing corn starch 5.0 – 10.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively.

MOP- M. oleifera leaf powder; G1CS10, G3CS10, G5CS10- granules containing gelatin 1.0 – 5.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; G1CS12.5, G3CS12.5, G5CS12.5-  granules containing gelatin 1.0 – 5.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively; P1CS10, P3CS10, P5CS10-  granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch  10% w/w  as binder and disintegrant respectively; P1CS12.5, P3CS12.5, P5CS12.5-granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch 12.5% w/w  as binder and disintegrant respectively; CS5CS10, CS7.5CS10, CS10CS10- granules containing corn starch 5.0 – 10.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; CS5CS12.5, CS7.5CS12.5, CS10CS12.5-  granules containing corn starch 5.0 – 10.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively.

 

The average moisture loss on drying for the powdered Moringa oleifera leaves was 7.93± 0.142%. This value is less than the officially allowed maximum ^[19] and the low value of moisture content could prevent bacterial, fungal or yeast growth. Table 1, shows some of the micromeritic properties of the granules and powdered leaf. The mean particle diameter for the ungranulated leave powder (MOP) was 192 µm, while those of the granules ranged between 194 µm (CS10CS12.5 – granules containing starch mucilage 10% w/w and starch powder 12.5% w/w as binder and disintegrant respectively) and 275 µm (P3CS10 – granules containing polyvinylpyrrolidone 3% w/w and starch powder 10% w/w as binder and disintegrant respectively).

                  

MOP- M. oleifera leaf powder; G1CS10, G3CS10, G5CS10- granules containing gelatin 1.0 – 5.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; G1CS12.5, G3CS12.5, G5CS12.5-  granules containing gelatin 1.0 – 5.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively; P1CS10, P3CS10, P5CS10-  granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch  10% w/w  as binder and disintegrant respectively; P1CS12.5, P3CS12.5, P5CS12.5-granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch 12.5% w/w  as binder and disintegrant respectively; CS5CS10, CS7.5CS10, CS10CS10- granules containing corn starch 5.0 – 10.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; CS5CS12.5, CS7.5CS12.5, CS10CS12.5-  granules containing corn starch 5.0 – 10.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively.

 

The flowability of a powder is an important property influencing several drug manufacturing steps. Flowability is affected by the physical properties of the powder, such as particle size and shape, the loading experienced by particles (gravity, interaction with air flow and container etc.), the current state of the powder (i.e. tap, free flowing etc.) and the processing environment (e.g. humidity). Particles larger than 250 μm usually flow freely while particles below 100 μm are generally cohesive and prone to flowability problems²⁹.

                   

MOP- M. oleifera leaf powder; G1CS10, G3CS10, G5CS10- granules containing gelatin 1.0 – 5.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; G1CS12.5, G3CS12.5, G5CS12.5-  granules containing gelatin 1.0 – 5.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively; P1CS10, P3CS10, P5CS10-  granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch  10% w/w  as binder and disintegrant respectively; P1CS12.5, P3CS12.5, P5CS12.5-granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch 12.5% w/w  as binder and disintegrant respectively; CS5CS10, CS7.5CS10, CS10CS10- granules containing corn starch 5.0 – 10.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; CS5CS12.5, CS7.5CS12.5, CS10CS12.5-  granules containing corn starch 5.0 – 10.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively.

 

The particle size distribution (PSD) of a powder defines the relative amounts of particles present, sorted according to size. The flow properties of particulate solids are also known to depend on the size distribution of particles^{30, 31}. The PSD of MOP is bimodal with the higher mode appearing below particle size of less than 500 µm. The second mode was at about 500 µm size and the proportion of particles whose sizes are greater than 500 µm is much lesser than those with sizes ≤ 500 µm (Fig. 1). The granules of G1CS10, CS5CS10, G3CS10, P3CS10, P5CS10, G1CS12.5, CS5CS12.5, P3CS12.5, CS7.5CS12.5, and G5CS12.5, all displayed bimodal PSD (Figs. 2, 3, 5, 6, 9, 11, 13, 15, 16 and 17). Among all these, CS5CS10 possessed the greatest percentage of granules with particle sizes > 500 µm. Although P3CS10 granules possessed the highest mean particle size (275 µm), the proportion of its granules with particle sizes < 500 µm is higher than those of CS5CS10 whose mean particle size is 255 µm (Table 1). All the granules with unimodal PSDs, P1CS10, CS7.5CS10, G5CS10, CS10CS10, P1CS12.5, G3CS12.5, P5CS12.5, (Figs. 4, 7, 8, 10, 12, 14 and 18), had larger proportions of granules with particle sizes less than 500 µm.

 

  MOP- M. oleifera leaf powder; G1CS10, G3CS10, G5CS10- granules containing gelatin 1.0 – 5.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; G1CS12.5, G3CS12.5, G5CS12.5-  granules containing gelatin 1.0 – 5.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively; P1CS10, P3CS10, P5CS10-  granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch  10% w/w  as binder and disintegrant respectively; P1CS12.5, P3CS12.5, P5CS12.5-granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch 12.5% w/w  as binder and disintegrant respectively; CS5CS10, CS7.5CS10, CS10CS10- granules containing corn starch 5.0 – 10.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; CS5CS12.5, CS7.5CS12.5, CS10CS12.5-granules containing corn starch 5.0 – 10.0% w/w and corn starch  12.5% w/w  as binder and disintegrant  respectively.

 

MOP- M. oleifera leaf powder; G1CS10, G3CS10, G5CS10- granules containing gelatin 1.0 – 5.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; G1CS12.5, G3CS12.5, G5CS12.5-  granules containing gelatin 1.0 – 5.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively; P1CS10, P3CS10, P5CS10-  granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch  10% w/w  as binder and disintegrant respectively; P1CS12.5, P3CS12.5, P5CS12.5-granules containing polyvinylpyrrolidone 1.0 – 5.0% w/w and corn starch 12.5% w/w  as binder and disintegrant respectively; CS5CS10, CS7.5CS10, CS10CS10- granules containing corn starch 5.0 – 10.0% w/w and corn starch  10%w/w  as binder and disintegrant respectively; CS5CS12.5, CS7.5CS12.5, CS10CS12.5-  granules containing corn starch 5.0 – 10.0% w/w and corn starch  12.5% w/w  as binder and disintegrant respectively.

 

These PSDs influenced the flow properties of the various granule batches and is evident in figures 19 and 22. MOP particles displayed the lowest flowability in comparison to all the granule batches as expected. Flowability is actually dependent on the attraction between particles, including friction and adhesion. Inter-particle friction mostly depends on the characteristics of outer surface of particles, which is in turn determined by the ingredient of the wall material and the preparation method to form the particles. Generally speaking, smoother surface results in smaller friction, while inter-particle adhesion is caused by intermolecular forces, such as van der Waals forces, local chemical bonds, electrostatic charges, and bridging forces. Apart from chemical compositions, particle size and size distribution are other two very important factors to determine particle flow property. Particle size influences contact area greatly. For bigger particles, gravity is generally greater than inter-particle adhesive force, making the flow easier. The relation between particle gravity and inter-particle adhesive forces and its influence on the particle flowability have been elucidated^{32, 33}. Small quantity of fine particles in larger particles would lead to good powder flowability because of the lubricating ability. Too many small granules would however increase the contact area, just as a broad particle size span will make the contact area larger and the flow more difficult. Wide particle distribution, including broad bimodal pattern, has been shown to do harm to the flow properties of pharmaceutical powders³⁴.

 

Tapping experiments usually give results that differ from those of free fall. This is traceable to the denser packing resulting from reorientation of particles during tapping and the filling of the spaces between larger particles by smaller ones. This is obvious in the values of Carr’s index and Hausner’s ratio (Figs. 20 and 21). Although MOP consistently possessed the highest values for both indices, except for G5CS10 and P1CS12.5, there is no significant difference (p > 0.05) between MOP Carr’s and Hausner’s indices and those of other granule batches. It therefore implies that for the granules resulting from this study, flow rate and angle of repose determinations gave a more reliable indication of their flow properties.

 

The particle densities of MOP and the granules ranged from 1.12 g/ml to 1.36 g/ml. These values ordinarily may seem  not to vary greatly, but on the application of one way ANOVA,  significant differences  were found to exist between the particle densities of MOP and those of granules formulated with either gelatin or corn starch BP (p < 0.05);  but none existed between the values for MOP and granules formulated with polyvinylpyrrolidone ( p > 0.05). This implies that gelatin and corn starch BP imparted better densification on the M. oleifera powder during the granulation process than did polyvinylpyrrolidone. Previous workers³⁵ had shown that  majority of APIs must be densified before manufacturing the final dosage form so that sufficiently high doses can be administered in a reasonably sized dosage form. This finding suggests that gelatin and corn starch BP are better binders for the densification of M. oleifera powder than polyvinylpyrrolidone. The relative densities of powdered pharmaceutical materials generally increase as the materials are processed into solid dosage forms. The higher the relative density of a powder bed, the lower its porosity and the better its packability. Furthermore, bulkiness, which is the inverse of bulk density, is a very important characterization property of powders, because it makes direct impression on the packaging and shipping cost of powders³⁵. MOP has high porosity and bulkiness in comparison to some of the granulated products especially G1CS10 (Figs. 23 and 24). The latter possessed the least porosity (best packability) and bulkiness (most economic packaging and shipping cost) among all the granulated products. These two properties suggest that G1CS10 granules will require a smaller sized capsule shell for encapsulation purpose, or give smaller sized tablets when compacted (these will enhance patients’ compliance) and cost less during shipping in comparison to the other granulated products or MOP.

 

CONCLUSION:

Micromeritic properties of pharmaceutical powders are among the primary parameters given serious consideration prior to their formulation into various solid drug delivery systems. Recent developments show that herbal products are becoming highly preferred to synthetic drugs, hence the obvious popularity of M. oleifera products. This study reveals from tapping experiments, which simulate the production process, that granulated M. oleifera products possessed much better micromeritic properties than ungranulated ones. In addition, albeit all the granulated products have similar flow properties, granules formulated with gelatin at 1% w/w and corn starch BP at 10% w/w as binder and disintegrant respectively, displayed the best packability and bulkiness and therefore is suggested to be the excipients of choice for the formulation of M. oleifera granules. 

 

REFERENCES

1.       Shanker K, Gupta MM, Srivastava SK, Bawankule DU,   Pal A, Khanuja SPS. Determination of  bioactive nitrile glycoside(s) in drumstick (Moringa oleifera) by reverse phase HPLC. Food Chemistry. 105; 2007: 376–382.

2.       Mishra G, Singh P, Verma R, Kumar S, Srivastav S,  Jha KK,  Khosa RL. Traditional uses, phytochemistry and pharmacological properties of Moringa oleifera plant: An overview. Der Pharmacia Lettre. 3(2); 2011: 141-164.

3.       Caceres A, Saravia A, Rizzo S, Zabala L, Leon ED, Nave F. Pharmacologic properties of Moringa oleifera: screening for antispasmodic, anti-inflammatory and diuretic activity. Journal of  Ethnopharmacology. 36; 1992: 233–237.

4.       Faizi S, Siddiqui BS, Saleem R, Siddiqui S, Aftab K, Gilani AH. Fully acetylated carbonate and hypotensive thiocarbamate glycosides from Moringa oleifera. Phytochemistry. 38; 1995: 957–963.

5.       Guevara  AP, Vargas C, Sakurai H, Fujiwara Y, Hashimoto K,  Maoka T. An antitumor promoter from Moringa oleifera Lam. Mutation Research. 440; 1999: 181–188.

6.        Marugandan S, Srinivasan K, Tandon SK, Hasan HA. Anti-inflammatory and analgesic activity of some medicinal plants and analgesic activity of some medicinal plants. Journal of Medical Aromatic Plants Science. 22; 2001: 56–58.

7.       Dangi SY, Jolly CI, Narayanan S. Anti-hypertensive activity of the total alkaloids from the leaves of Moringa oleifera. Journal of Pharmaceutical Biology. 40; 2002: 144–148.

8.       Kar A, Choudhary BK, Bandyopadhyay NG. Comparative evaluation ofhypoglycaemic activity of some Indian medicinal plants in alloxan diabetic rats. Journal of Ethnopharmacology. 84; 2003: 105–108.

9.       Mehta K, Balaraman R, Amin AH, Bafna PA, Gulati OD. Effect of fruits of Moringa oleifera on the lipid profile of normal and hypercholesterolaemic rabbits. Journal of  Ethnopharmacology. 86; 2003: 191–195.

10.     Sahoo AK. Plants used as ophthalmic drugs in Phulbani Orisa. Glimp Ind Pharmacology. 1995.

11.     Ezeamuzie IC, Ambakedermo AW,  Shode FO. Antiinflammatory effect of Moringa oleifera root extract. International Journal of Pharmacognosy. 34(3); 1996: 207 - 212.

12.     Rathi BS, Bodhankar SL  Baheti AM. Evaluation of aqueous leaves extract of Moringa oleifera Linn for wound healing in albino rats. Indian Journal of  Experimental  Biology.44; 2006: 898 - 902.

13.     http://geniusherbs.trustpass.alibaba.com/productshowimg/124121632-103175773/Moringa_oleifera_Granules_for_Sales.html. Accessed on June 6th 2012.

14.     www.alibaba.com/showroom/moringa-powder.html. Accessed on June 6th 2012.

15.     Rajesh A, Yadav N. Pharmaceutical Processing – A Review on Wet Granulation Technology. International Journal of Pharmaceutical Frontier Research.1 (1); 2011: 65-83.

16.     Boerefijn R, Hounslow MJ.  Studies of fluid bed granulation in an industrial R&D context. Chemical Engineering Science. 60; 2005: 3879-3890.

17.     Tousey MD. The Granulation Process 101 Basic Technologies for Tablet Making. Pharmaceutical Technology (Tableting and Granulation). 26; 2002: 8 – 13.

18.     Sinko PJ. Martin’s physical pharmacy and pharmaceutical sciences; 6^th edition, Lippincott Williams and Wilkins: Philadelphia, 2011.

19.     British Pharmacopoeia Vol IV Her Majesty Stationery Office: London, 2009.

20.     Odeku OA, Itiola OA. Characterization of khaya gum as a binder in a paracetamol tablet formulation. Drug Development and Industrial Pharmacy. 28(3); 2002: 329 – 337.

21.     Rudnic EM, Schwartz JB. Oral solid dosage forms. In R. Hendrickson (Ed.), Remington: The Science and Practice of Pharmacy, 21st ed., Lippincott William and Wilkins: Philadelphia, 2006: 889 – 928.

22.     Armstrong NA. Tablet Manufacture. In James Swarbrick and James C. Boylan (Eds), Encyclopedia of Pharmaceutical Technology, 2^nd ed., Vol 3; Marcel Dekker Inc.: New York, 2002: 2713 – 2732.

23.     Brittain HG. What is the “correct” method to use for particle size determination? Pharmaceutical Technology. July; 2001: 96-98.

24.     Brittain HG. Particle size distribution, part I: Representation of particle shape, size, and distribution. Pharmaceutical Technology. December; 2001: 38-45.

25.     Brittain HG. Particle size distribution II: The problem of sampling powdered solids. Pharmaceutical Technology. July; 2002: 67-73.

26.     Brittain HG. Particle size distribution III: Determination by analytical sieving. Pharmaceutical Technology. December; 2002: 56-64.

27.     Ansel HC, Allen LV, Poporich NG. Powders and granules. In Ansel’s Pharmaceutical dosage forms and drug delivery systems, 8^th ed. Lippincott Willians and Wilkins: New Delhi, 2007.

28.     Ohwoavworhua FO, Adelakun TA, Kunle OO. A comparative evaluation of the Flow and Compaction characteristics of a-cellulose obtained from Waste Paper. Tropical Journal of Pharmaceutical Research. 6(1); 2007: 645 – 651.

29.     Soppelaa I, Airaksinenb S, Murtomaac M, Tenhoc M, Hataraa J, Raikkonena H, Yliruusia J, Sandlerb N. Investigation of the powder flow behaviour of binary mixtures of microcrystalline celluloses and paracetamol. Journal of Excipients and Food Chemistry. 1(1); 2010: 55 – 67.

30.     Xinde XU,  Shanjing YAO, Ning HAN,  Bin SHAO.Measurement and Influence Factors of the Flowability of Microcapsules with High-content β-Carotene. Chinese Journal of Chemical Engineering. 15(4); 2007: 579 - 585.

31.     Vinita K, Shrikant G, Mahesh P. Manipulation of physical functionality of bulk drug powder: agglomerate size approach. International Journal of Drug Development and Research. 3(2); 2011: 344 – 351.

32.     Santomaso A, Lazzaro P. Transition to movement in granular chute flows. Chemical Engineering Science. 56; 2003:3563 – 3573.

33.     Li Q, Rudolph V, Weigl B, Earl A. Interparticle van der Waals force in powder flowability and compactibility. International Journal Pharmaceutics. 280; 2004:77 – 93.

34.     Hancock BC, Joshua TC, Mullarney MP, Andrey VZ. The Relative Densities of Pharmaceutical Powders, Blends, Dry Granulations, and Immediate-Release Tablets. Pharmaceutical  Technology. April; 2003:64 -80.

35.     www.calpoly.edu/~DPTC .Dairy ingredients fax Vol. 3 No. 1. Accessed on July 17th 2012.

 

 

 

Received on 20.11.2012       Modified on 24.11.2012

Accepted on 28.11.2012      © RJPT All right reserved