Influence of Electrolyte Type, pH, Temperature and Aging on the Viscosity Property of Okra Gum as a Suspending Agent in Paracetamol Suspension Pharmaceutical and Biosciences Journal Available at www.ukjpb.com

The purpose of this study was to investigate the influence of electrolyte type, pH, temperature and aging on the viscosity property of okra gum using paracetamol as model drug. Paracetamol (125 mg/ 5 mL) suspension containing okra gum particles of undersize 180 µm as suspending agent was formulated. Similar suspension of paracetamol was formulated using tragacanth gum as a suspending agent for comparison. Effect of electrolyte type, pH, temperature and aging on the viscosity property of okra gum in paracetamol suspension was evaluated using standard methods. Addition of electrolytes, changes in pH, increase in temperature and increase in storage time were shown to decrease the viscosity of the paracetamol suspension. The effect of temperature and aging on the viscosity of the suspension formulation containing okra gum was more pronounced than on the formulation containing tragacanth gum. Conversely, the effect of alkaline pH and type of electrolyte on the viscosity of the suspension formulation containing tragacanth gum was more pronounced than on the formulation containing okra gum. On the basis of these, formulators and caregivers may consider these factors when designing or using pharmaceutical suspensions containing natural gums such as okra and tragacanth as viscosity enhancing agents.


Introduction
Viscosity is termed as resistance to flow 1 . Viscosity of a pharmaceutical suspension is of great importance because it affects stability, redispersibility, drug release and pourability of a suspension 2 . A good suspension should have adequate viscosity to ensure that the dispersed drug particles remain suspended long enough to maintain stability 3 .
A good suspension should also have reasonable viscosity to ensure that drug release process is not impeded. A study by Venkateswarlu, Chnadrasekhar and Ramachandra 4 found out that drug release from flucloxacillin suspension decreased as viscosity increased due to formation of high viscosity regions on the layer surrounding drug particles and in the bulk medium due to reduced diffusion process caused by hydrated polymer chains.
The ease with which a suspension pours during withdrawal depends on the viscosity of the suspension; with less viscous pouring more easily than more viscous suspensions 5 . Adequate viscosity ensures the caregiver is able to pour the suspension from the packaging container without difficult during administration.
The viscosity of a medium is not constant and factors such as concentration of suspending agent, pH changes, electrolytes (ionic strength), sugars, ageing, temperature and type of agitation have been reported to affect viscosity of a suspension 6  125 mg / 5 mL with require that some of the paracetamol powder is suspended in water thus paracetamol is a candidate for formulation as a suspension. It is an indiffusible solid 7 that does not remain suspended for enough time to allow withdrawal of uniform doses. Therefore, to formulate paracetamol suspension, a suspending agent such as okra gum is required to increase the viscosity of the disperse system, reduce settling of the suspended drug particles, maintain uniform dispersion and prevent cake formation 3 .
Okra gum has been used as suspending agent in pharmaceutical suspension formulations 7,8 . However, it is not known how electrolytes, temperature, pH and aging can affect the viscosity property of okra gum when used in these formulations. Therefore, the study sought to provide knowledge on the influence of these properties on the viscosity property of okra gum when used in a formulation, an important aspect in the development and use of pharmaceutical suspensions.

Collection and Identification of Okra Plant Pods
Okra pods were obtained from Faringada market at Jos, Plateau State in September, 2018. Whole okra plant with pods was taken to a botanist at the College of Forestry, Jos for identification and the herbarium voucher number was FHJ 241.

Extraction and Purification of Okra Gum
The method of Farooq, Malviya and Sharma 9 was adopted. Fresh Okra pods were washed with purified water, sliced, air-dried in the laboratory and weighed. The dried sliced okra was macerated in cold water for 24 hours to extract the mucilage and the dispersion was separated from the chaff using a muslin cloth. The mucilage was centrifuged (Centrifuge, Mistral 1000, UK) at 4500 rpm for ten minutes and then treated severally with 96 % ethanol to precipitate the gum. The gum was air dried, pulverized, The powdered okra gum was passed through sieve undersize 180 µm to obtain undersize 180 µm particle size distribution.
Tragacanth gum was treated in similar way and used for comparison.

Preparation of Oral Paracetamol Suspension
The method of Venkateswarlu, Chnadrasekhar and Ramachandra 4 was adopted. A paracetamol suspension to deliver a dose of 125 mg/5 mL was formulated using 0.6 % w/v of okra gum and tragacanth gum as suspending agents. Desired quantities of paracetamol powder and excipient powders (Table   1) were finely ground, screened through a sieve of undersize 180 µm and weighed.
Sodium lauryl sulphate was mixed with sodium citrate in a mortar using a pestle for two minutes to form a mix. To the mix, sodium benzoate was added and mixed for two minutes. Gum powder was added to mix and mixed for three minutes. Paracetamol powder was added to the mix and mixed for three minutes to form a blend of dry powder suspension. A 100 mL of water was added in small quantities while mixing until a suspension was formed.
The components of the oral reconstitutable suspensions are shown in table 1.

Effect of pH on viscosity of the paracetamol suspension
The method of Kadiri and Okafor 11 was adopted. A 1 mL of 0.1 N hydrochloric acid (HCl) was added to the formulated paracetamol suspension and the suspension was made into 50 mL. The viscosity of the suspension was determined using a digital rotational viscometer. The mean of the three determinations was recorded. The same process was repeated using 1 mL of 0.1 N sodium hydroxide (NaOH).

Effect of temperature on viscosity of the paracetamol suspension
The method of Kadiri and Okafor 11 was adopted. A 50 mL of the suspension was transferred into the viscometer cup and after one minute, viscosity was determined using rotor 2 spindle. The suspensions were then stored in a refrigerator (HR 170T) at 4 0 C and in a dryer (Gallenkamp drying cabinet, Germany) at 40 0 C for twenty-four hours and the viscosity of the suspensions were measured using a digital rotational viscometer. The mean of the three determinations was recorded.

Effect of electrolyte type on viscosity of the paracetamol suspension
The method of Kadiri and Okafor 11 was adopted. A 1 mL of 0.5% w/v sodium chloride, calcium chloride or aluminium chloride was added to 50 mL of the formulated paracetamol suspensions and allowed to stand for twenty-four (24) hours. The viscosity of the suspensions was measured using a digital rotational viscometer.
The mean of the three determinations was recorded.

Effect of ageing on viscosity of the paracetamol suspension
The method of Kadiri and Okafor 11 was adopted. A 50 mL of the paracetamol suspension was transferred into the viscometer cup and viscosity was determined using Rotor 2 spindle. The suspension was then stored at room temperature for two months and the viscosity of the suspension was measured using a digital rotational viscometer. The mean of the three determinations was recorded. These findings augment the findings by Kadiri and Okafor 11 which found out that the impact of changes in pH on the viscosity of the medium depends on the initial pH and suspensions containing weakly acidic gums are greatly affected by strong acids such as hydrochloric acid.  Table 3 shows the effect of temperature on viscosity of respectively. The drop in viscosity was more in the suspension containing okra gum than in the suspension containing tragacanth gum.   Table 4  Addition of electrolytes to the paracetamol suspensions decreased their viscosity and the impact increased as the charge on the ion increased from monovalent to trivalent. This is possibly due to electrolytes changing the charge density thus affecting the intermolecular interactions. These findings agrees to early findings by Kadiri and Okafor 11 which reported that addition of electrolytes to metronidazole suspension decreased the viscosity.  respectively indicating a decrease of 13.80 % and 5.14 % respectively. The viscosity of the suspension formulation containing okra gum dropped more than that of the suspension formulation containing tragacanth gum.

Conclusion
The viscosity property of okra gum in paracetamol suspension was susceptible to type of electrolyte, pH, temperature and aging and thus formulators and caregivers should consider these factors when designing or using pharmaceutical suspensions containing natural gums such as okra and tragacanth as viscosity enhancing agents. The study implies that when reconstituting dry suspensions that have been formulated using natural gums such as okra gum, where possible, it is appropriate to use deionized water, reconstitute and store within the recommended temperature to avoid alteration of viscosity which may affect the performance and bioavailability.

Acknowledgment
The author would like to acknowledge the African Centre of Excellence on Phytomedicine Research and Development (ACEPRD), University of Jos for the financial support.

Conflict of interest
Nil 7 Author's contributions VON came up with the idea, conducted literature review, designed and carried out data collection, and drafted the manuscript. JIO offered guidance during development of the idea and data collection, and reviewed the manuscript. All the authors read and approved the final copy of the manuscript.