Formulation and evaluation of flow properties of co-processed Caesalpinia gum and annealed maize starch

Ibukun O. Adeleke¹*, Ignatius S. Okafor²

¹Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Igbinedion University Okada, Nigeria.

²Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, University of Jos, Jos, Nigeria.

*Corresponding Author E-mail: ibukun.adeleke@iuokada.edu.ng

ABSTRACT:

The shortcomings of existing excipients such as low dilution potential and poor die filling as a result of poor flow properties have been a problem in direct compression tableting. The objective of this study was to formulate and evaluate the flow properties of co-processed Caesalpinia gum and annealed maize starch at various ratios as a potential direct compression excipient. Caesalpinia gum was extracted from the fresh seeds of Caesalpinia pulcherrima plant (Family Caesalpiniaceae). The gum was co-processed with the annealed maize starch at varying ratios in a co-solvent system consisting of acetone and distilled water (2:1). The flow properties of the co-processed excipients were determined using standard methods such as bulk density, tapped density, particle density, angle of repose, Hausner ratio, and Carr’s index. Cellactose was used as a standard for comparison. It was found out that Batch III (15:85) Caesalpinia gum: annealed maize starch gave the best flow among the batches of the co-processed excipients containing Caesalpinia gum and annealed maize with angle of repose of 31.48⁰±0.74, bulk, tapped, particle density of 0.42±0.06 g/cm³, 0.49±0.12 g/cm³, and 1.56±0.07 g/cm³ respectively, Carr’s index of 15.79 %, and Hausner ratio of 1.19. The study confirmed that the co-processed excipient flowed well in comparison with Cellactose^® 80 in flowability properties which was used as a standard for comparison, and can be used as a substitute for the commercially available co-processed excipient Cellactose^® 80.

KEYWORDS: Flow properties, Co-processed excipient, Direct compression excipient, Caesalpinia gum, Annealed maize starch

INTRODUCTION:

Direct compression is the process by which tablets are prepared directly from the powder blends of active ingredients and suitable excipients without a preliminary granulation step^1,2. In recent years, most of the pharmaceutical manufacturing industries opt for direct compression tableting due to the fact that it requires fewer processing steps, elimination of heat and moisture, economy, and improved drug stability compared with wet granulation technique. Direct compression method of production is cost effectiveness since it requires fewer unit operations. This means less equipment, lower power consumption, less space, less time and less labor leading to reduced production cost of tablets. Direct compression is more suitable for moisture and heat sensitive active pharmaceutical ingredients, since it eliminates wetting and drying steps and increases the stability of active ingredients. Changes in dissolution profiles are less likely to occur in tablets made by direct compression on storage than in those made from granulations. The tablets prepared by direct compression disintegrate into active pharmaceutical ingredients particles instead of granules that directly come into contact with dissolution fluid and exhibits comparatively faster dissolution. The high compaction pressure involved in the production of tablets by slugging or roller compaction can be avoided by adopting direct compression. The chances of wear and tear of punches and dies are less Since ingredients are processed for a shorter period of time, the chance for contamination is low and also due to the absence of water, chance of microbial growth is minimal^{1,3,4, 5, 6}. The dry state of the materials during mixing may induce static charges and lead to segregation. This may lead to the problems like weight variation and drug content non-uniformity. Directly compressible excipients are the speciality products produced by spray drying, fluid bed drying, roller drying or co-crystallization; hence, the products are relatively costly than the respective raw materials. In direct compression method, lubricants have more adverse effects on the filler, which exhibit almost no fracture or shear on compression e.g. Starch 1500^®. The softening effects as well as the hydrophobic effect of alkaline stearates can be controlled by optimising the length of blending time to as little as 2 to 5 min^{1, 3, 4,5}. A directly compressible excipient should be free flowing. Flowability is required in the case of high-speed rotary tablet machines in order to ensure homogenous and rapid flow of powder for uniform die-filling. Many common manufacturing problems are attributed to incorrect powder flow, including non-uniformity in blending, under or over dosage and inaccurate filling^1,7. Nevertheless, direct compression is more prone to segregation due to the difference in density of the active pharmaceutical ingredients and excipients. Most of the directly compressible materials can accommodate only 30-40 % of the poorly compressible active ingredients and are relatively costly^{1,2, 5,8}. Consequently, there is need to develop affordable excipients. In addition to the development of directly compressible excipients by the modification of a single substance, co-processing of two or more components is used to prepare directly compressible excipients. Co-processed excipients are combinations of two or more excipients that possess performance advantages that cannot be achieved using a physical admixture of the same combination of excipients. The co-processed excipients are introduced to achieve better flow, better dilution potential, and reduced fill weight variation in comparison with a single substance or the physical admixture. Several of these excipients are commercially available. Examples include Cellactose^® (lactose-cellulose), Avicel^® CE-15 (microcrystalline cellulose and guar gum), Ludipress^® (lactose, polyvinylpyrrolidone, and crosspovidone), and Prosolv^® (microcrystalline cellulose and silicon dioxide)^{1, 8, 9,10}. The study is aimed at evaluating the flow properties of co-processed caesalpinia gum and annealed maize starch at various ratios of the gum and starch using Cellactose as standard for comparison.

MATERIALS AND METHODS:

Materials             

Maize starch (Sigma-Aldrich, France), cellactose^® 80 (Meggle Group Wasserburg, Germany), acetone (Merck, Germany), caesalpinia gum locally processed from the fresh seeds of Caesalpinia pulcherrima in western region of Nigeria and authenticated by Ibhamesebhor G and Omomoh B.E, Botany Department, Obafemi Awolowo University, Ile-Ife (authentication no IFE 17226).

Methods

Extraction of Caesalpinia gum

The method reported by Senthil et al.¹¹ was adapted. Fresh seeds obtained from Caesalpinia pulcherrima plant were washed, after which the seed coats were removed. The endosperms were soaked in distilled water for 24 h, after which the endosperms were wet-milled. The slurry obtained was allowed to stand for 12 h, wet-milled and filtered using a muslin bag. The filtrate was kept at 12 ⁰ C for 6 h, dehydrated with acetone, and air dried. It was further dried in an oven (Gallenkhamp BS, England) for 2 h at 50 ⁰ C. The product obtained was pulverized in a pulverizer (Rocklab, New Zealand), passed through sieve number 180 µm mesh and bottled for further use.   

Modification of maize starch

The method reported by Adebowale et al.¹² was adapted in the preparation of annealed maize starch. To 500 g of maize starch was added 6 litres of distilled water and heated at 50 ⁰ C for 24 h in an oven. The excess water was decanted and the starch was air-dried. The dried starch was passed through sieve number 250 µm mesh and bottled for further use.

Preparation of co-processed caesalpinia gum-annealed maize starch

The method of Chandile et al.¹³ was adapted. To homogeneous mixture of caesalpinia gum and annealed maize starch in the ratios listed in Table 1 was added a solution of acetone and distilled water in ratio 2:1 respectively and stirred continuously to obtain a wet coherent mass. This wet coherent mass was wet-screened using a 1000 µm mesh sieve. The wet granules obtained were dried in an oven (Gallenkhamp BS, England) at 50 ^oC for 1 h. The dried granules were then dry-screened 500 µm mesh sieve and stored in airtight bottle.

Table 1. Formula for Preparation of Batches of Co-processed Excipient

Materials	Batch
	I	II	III	IV	V
Caesalpinia gum (% w/w)	5	10	15	20	25
Annealed maize starch (% w/w)	95	90	85	80	75

Determination of the flow properties of co-processed excipients

Bulk density

Weighed quantity of the co-processed excipients was taken in a graduated measuring cylinder. The volume V₀ (bulk volume) occupied by each of the excipient at zero pressure was obtained. The bulk density was calculated as the weight per unit volume of the excipient. The bulk density was calculated as a mean of three determinations.

Tapped density

Weighed quantity of the co-processed excipients which was taken in a graduated measuring cylinder above was tapped on a soft padded table surface 100 times. The tapped volume (V₁₀₀) was obtained. The tapped density was calculated as the weight per unit volume of the excipient. This was calculated as a mean of three determinations.

Angle of repose

Angle of repose was measured by fixed height method¹⁴.

Carr’s index

This was calculated using the equation:

              (Tapped density-Bulk density)

CI= ----------------------------------- X 100     --Equation 1

               (Tapped density)

Where:

CI = Carr’s index

Hausner ratio

Hausner ratio, HR was calculated as the ratio of tapped density to bulk density of the excipients.

              (Tapped density)

HR= -----------------------------------                --Equation 2

               (Bulk density)

Particle density

A 25 mL pycnometer was weighed, after which it was filled with acetone as displacement fluid and weighed. The weight was noted. The acetone was emptied from the pycnometer. Then 1 g of each of the batches I to V of co-processed excipients and cellactose was introduced into the already weighed 25 mL pycnometer and then filled with acetone, after which it was weighed. This experiment was performed in triplicate. The particle density of each batch of the excipient was calculated using the formula shown below.

             (1 g of excipient X specific gravity of solvent)

Particle density= -----------------------------   ---Equation 3

                                (w1+w2)-w3)

Where:

W1 = weight of pycnometer + acetone (g)

W2 = weight of excipient (g)

W3 = weight of pycnometer + acetone + excipient (g)

                                    (weight of acetone)

Specific gravity = ------------------------------- -Equation 4

of solvent (acetone)       (volume of acetone)

Porosity

The porosity of co-processed excipients was determined from the equation 1-RD, where RD is the relative density obtained from the equation, RD = Bulk (loose) density/Particle density.

Statistical Analysis

Analysis of Variance was carried out to analyze the results obtained for the density properties and angle of repose of the co-processed excipients containing various ratios of caesalpinia gum and annealed maize starch using Statistical Package for the Social Sciences (SPSS) software. This was used to determine if there were any statistically significant differences.

RESULTS AND DISCUSSION:

Table 2 shows the flow properties of the batches of the co-processed excipient containing caesalpinia gum and annealed maize starch in various ratios. The angle of repose of the co-processed excipient made with 15% caesalpinia gum and 85% annealed maize starch (Batch III) gave the lowest value of angle of repose of 31.48⁰, while that made with 10% caesalpinia gum and 90% annealed maize starch (Batch II) gave the highest angle of repose of 36.37⁰. The rank order for angle of repose is II > I > V>IV>III. The angle of repose of Cellactose was found to be 27.31⁰. As a general rule powders with angle of repose greater than 50^o have unsatisfactory flow properties whereas minimum angles close to 25^o corresponds to very good flow¹⁵. All the co-processed excipients possessed satisfactory flow properties with angle of repose ranging from 27.31 ^o to 36.81^o.  The highest bulk density and tapped density of 0.47 g/cm³ and 0.58 g/cm³ respectively was reflected in batch I containing 5% caesalpinia gum and 95% annealed maize starch. The bulk density of caesalpinia gum – annealed maize starch co-processed excipients. It was found that the particle density of the co-processed excipient containing Caesalpinia gum and annealed maize starch increased from batch I to V due to increase in the concentration of the gum. The bulk and tapped density of a powder describes its packing behavior during tabletting^16,17.

Table 2. Flow Properties of Co-processed excipients

Batch	Angle of repose (⁰)	Bulk density (g/cm^3)	Tapped density (g/cm^3)	Particle density (g/cm^3)	Carr’s index (%)	Hausner ratio
I (5:95)	36.00±0.76	0.47±0.12	0.58±0.12	1.34±0.17	18.56	1.23
II (10:90)	36.37±0.81	0.43±0.17	0.53±0.12	1.56±0.12	18.58	1.23
III (15: 85)	31.48±0.74	0.42±0.06	0.49±0.12	1.56±0.07	15.79	1.19
IV (20:80)	32.49±0.87	0.42±0.00	0.52±0.00	1.63±0.03	19.05	1.24
V (25:75)	33.49±0.74	0.42±0.06	0.52±0.06	1.66±0.03	19.68	1.25
Cellactose	27.31±1.00	0.45±0.00	0.54±0.05	2.59±0.01	15.77	1.18

An increase in the tapped density is an advantage in tabletting because the fill volume of the die would be reduced. An increase in tapped density was observed in all the batches of the co-processed excipients. This implies that the co-processed excipients possessed good flowability, consequently, complete filling of the die, uniformity of weight and content of compressed tablets would be achieved when employed in tabletting. The rank order for Carr’s index of the co-processed excipient is V > IV > II > I > III > Cellactose. This shows that batch V containing 25% of ceasalpinia gum and 75% annealed maize starch possesed the highest Carr’s index of 19.68 % while batch III containing 15% caesalpinia gum and 85% annealed maize starch gave the lowest Carr’s index of 15.79 % among the five batches of caesalpinia gum-annealed maize starch co-processed excipients.

The rank order for Hausner ratio of the caesalpinia gum–annealed maize starch co-processed excipients and cellactose is as follows: V > IV > I, II > III > Cellactose. This reflects that batch V gave the highest Hausner ratio value of 1.25 while batch III gave the lowest value of 1.19 among the five batches of caesalpinia gum-annealed maize starch co-processed excipients, while Cellactose gave Hausner ratio of 1.18. The bulk and tapped densities were used in the determination of Carr’s index and Hausner ratio.  The Hausner ratio has been used to predict the flow behaviour of powdered solids¹⁶. As a general rule Hausner ratio values less than 1.25 indicates good flow, while greater than 1.25 indicates poor flow¹⁵. All the batches gave good flow property and would therefore be of advantage in direct compression tableting. Table 3 shows the results obtained for the porosity of the co-processed excipients. From the results, it was found that the co-processed excipients compared well with Cellactose^®80 which gave the highest value of porosity. The higher the porosity of a powder or granules the higher will be its flow ability.

Table 3    Porosity of co-processed excipients

Co-processed excipients	Porosity
Batch I (5:95)	0.65
Batch II (10:90)	0.72
Batch III (15:85)	0.69
Batch IV (20:80)	0.68
Batch V (25:75)	0.69
Cellactose	0.83

CONCLUSION:

The study confirmed that the co-processed excipient flowed well in comparison with Cellactose^® 80 which was used as a standard for comparison, considering the flowability properties, and can be used as a substitute for the commercially available co-processed excipient Cellactose^® 80.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

REFERENCES:

1. Gohel MC. Jogani PD. A review of co-processed directly compressible excipents. Journal of Pharmacy and Pharmaceutical Sciences. 2005; 8(1): 76-93. www.cspscanada.org

2. Avinash G. Rahul KP. Ajay KS. Purnima DA. A novel directly compressible co-processed excipient for sustained release formulation. Journal of Applied Pharmaceutical Science. 2013; 3(9): 89-97. DOI: 10.7324/JAPS.2013.3917

3. Dokala GK. Pallavi C. Direct compression- An overview. International Journal of Research in Pharmaceutical and Biomedical Sciences. 2013; 4(1): 155-158.  

4. Chowdary KPR. Ramya K. Recent research on co-processed excipients for direct compression- A review. International Journal of Comprehensive Pharmacy. 2013; 4(2): 1-5.  

5. Mohammed KI. Pranjal KS. Mohd S. Ashif I.  Monika S. Recent advances in direct compression technique for pharmaceutical formulations. International Journal of Pharmaceutical Research and Development. 2014; 6(1): 49-57.  

6. Melissa M. Ricardo V. Therese D. Development of a new formulation for direct compression of a natural product. Journal of Pharmaceutical Technology and Drug Research. 2015; 4(2): 1-6. doi: 10.7243/2050-120X-4-2

7. Adeoye O. Alebiowu G. Flow, packing, and compaction properties of novel co-processed multifunctional directly compressible excipients prepared from tapioca starch and mannitol. Pharmaceutical Development and Technology. 2014; 19(8), 1-10. DOI: 10.3109/10837450.2013.840843

8. Liew KB. Anand G. Uttam KM. A review on co-processed excipient: current and future trend of excipient technology. International Journal of Pharmacy and Pharmaceutical sciences. 2019; 11(1): 1-9. DOI:10.22159/ijpps.2019v11i1.29265

9. Vasinee L. Narueporn S.  Poj K. Spherical composite particles of rice starch and microcystalline cellulose: A new co-processed excipient for direct compression. Journal of the American Association of Pharmaceutical Scientists. 2004; 5(2): 40-49. DOI: 10.1208/pt050230

10. Camargo JR. Assessment of cellulose II and silicon dioxide as a platform to enhance excipient functionality. Published doctoral thesis, University of Iowa, Iowa. 2011.

11. Senthil V. Gopalakrishnan S. Sureshkumar R. Jawahar N. Ganesh GNK. Nagasamyvenkatesh D. Mucoadhesive slow release tablets of theophylline: Design and evaluation. Asian Journal of Pharmaceutics. 2010; 4(1): 64-68. DOI:10.4103/0973-8398.63979

12. Adebowale KO. Olu-Owolabi BI. Olayinka OO. Lawal OS. Effect of heat moisture treatment and annealing on physicochemical properties of red sorghum starch. African Journal of Biotechnology. 2005; 4(9): 928-933.  

13. Chandile GK. Kumar U. Kakade SM. Rajasekar S. Jadhav R.T. Development and evaluation of haloperidol orally disintegrating tablets using novel co-processed superdisintegrants. International Journal of Resource Pharmaceutical Science. 2011; 2(3): 348 -352.  

14. Adeleke IO. Ayoola AO. Formulation and evaluation of co-processed acacia gum and potato starch. Journal of Research in Pharmaceutical Science. 2022; 8(5): 1-10.  

15. Aulton ME. Powder flow. In: Pharmaceutics: The Science of Dosage Form Design,9thed, 610. London: Churchill Livingstone. 1999; ISBN: 0-443-05756-7

16. Okafor IS. A comparative study of modified starches in direct compression tableting. Published master thesis, University of Nigeria, Nsukka. 1990

17. Okunola A. Odeku OA. Compressional characteristics and tableting properties of starches obtained from four dioscorea species. Farmacia. 2009; 57(7): 756-770.

Received on 15.05.2025      Revised on 25.06.2025

Accepted on 29.07.2025 Published on 25.08.2025

Available online from August 25, 2025

Asian J. Pharm. Res. 2025; 15(3):229-233.

DOI: 10.52711/2231-5691.2025.00037

©Asian Pharma Press All Right Reserved

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.