Stability and flow behaviour of barium sulphate suspension and the preparation of stable barium sulphate suspension for medical use

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1 Journal of Scientific & Industrial Research Vol. 64, April 2005, pp Stability and flow behaviour of barium sulphate suspension and the preparation of stable barium sulphate suspension for medical use Ahindra Nag* Chemistry Department, Indian Institute of Technology, Kharagpur Received 07 October 2004; accepted 09 February 2004 Stability and flow behaviour of concentrated barium sulphate suspension (BSS) was studied in the presence of sodium carboxy methyl cellulose (NaCMC), bentonite and poly vinyl pyrrolidone (PVP). NaCMC (0.2 %) showed maximum viscosity (50 %), maximum sedimentation volume of BSS and maximum (0.4 %) adsorption of NaCMC by BSS. Bentonite and PVP had no significant effect on sedimentation volume of BSS but increased the viscosity. The radiological studies on the X-ray picture of rabbit using BSS (50 %) and NaCMC (0.2 %) exhibited poor contrast of the stomach region. To increase the stability, suspension was mixed with tri sodium citrate (4 %). The X-ray picture of rabbit showed good contrast of the stomach as well as the small intestine region. Key words: Barium sulphate suspension, Additives, Sodium carboxy methyl cellulose,trisodium citrate, Viscosity, Rheogram template, Adsorption studies, Stability of suspension and Gastrointestinal tract, X-ray studies IPC Code: A 61 K 49/00 Introduction Barium sulphate suspension (BSS) is frequently used for the diagnosis of various diseases such as gastric and duodenal ulcer by barium meal 1, gastric carcinoma, specially its early stages and ampullary carcinoma by air contrast studies with barium sulphate 2, small intestinal mal absorption states and carcinoma of the colon by barium enema method 3. Many food additives have been used by various workers 1-4 to improve the quality, taste, prevention against flocculation and sedimentation of BSS. However, very little information 3,4 is available on the flow properties of BSS in the presence and absence of various food additives. BSS for radiological investigations should be stable throughout the whole range of ph from stomach to ileum. Viscosity of BSS should be such that it can pass through the gastrointestinal tract easily. BSS should also coat uniformly the walls of membrane during passage through the gastrointestinal tract. In the present paper, an attempt has been made to study the rheological and sedimentation behaviour of BSS in the presence of various additives in order to prepare a stable radioopaque food colloid that can be used for medical investigations. *Fax: ahinnag@ chem.iitkgp.ernet.in Materials and Methods All the glass apparatus used were washed with chromic acid and sulphuric acid mixtures. The surface tension of distilled water was 72.0 dynes/cm at 25 o C. All the additives (PVP, bentonite & NaCMC) were purchased from BDH Company, England. Trisodium citrate was of A R grade quality. Viscosity of aqueous solutions of the additives (measured by Brookfield viscometer) varied with time due to the change of the extent of aggregation of additive molecules with time. To obtain constant viscosity, the additives were dissolved in water and continuously stirred in a blender at 4000 rpm until they reached the constant viscosity. Barium sulphate powder (radio-opaque quality) was purchased from E Merck, West Germany. Moisture content (0.3 %) was determined by heating powder at 600 o C for 8 h. The surface area of barium sulphate particles, determined by palmitic acid adsorption 5, was 8.0± 0.5 m 2 /g. The ph of the suspension was maintained by adding either HCl or NaOH solution, and was measured with the help of Elico 120 digital ph-meter. Determination of Viscosity of BSS The apparent viscosity was measured with the help of Brookfield Synchrolectic Viscometer, Model LVT (Brookfield Engineering Laboratories, Stoughton, USA) with eight speeds ( rpm). In this

2 NAG: STABILITY AND FLOW BEHAVIOUR OF BARIUM SULPHATE SUSPENSION 269 method, a spindle, driven by a calibrated spring, is allowed to rotate at constant speed and the instrument measures the torque necessary to overcome the resulting viscous drag. For a given speed, it produces dial reading proportional to the viscosity. The viscosity is measured by multiplying the dial reading by a suitable 'factor' supplied with the instrument. With this procedure, correct apparent viscosity can be obtained for the Newtonian fluids whose value becomes independent of the shear rate. In the non- Newtonian system, the apparent viscosity becomes a function of shear rate. The 'dial viscosity' differs from the apparent viscosity under these circumstances and the magnitude of the error, measured by 'Rheogram Template' method, increases with increasing deviation of the flow system from the Newtonian behaviour 6. The method consists of the determination of shear thinning or shear thickening index (STI) values from the plot of log (dial reading) against log (rpm) by matching against a standard template. When STI equals unity, the behaviour of the fluid becomes Newtonian or shear thickening. For STI greater than one, the fluid is called shear thinning, or pseudoplastic. For known value of STI, well-defined shear rate at a particular rpm and the corresponding apparent viscosity can be calculated from the relations: Shear rate (sec -l ) = K l STI Apparent viscosity (cp) = K 2 dial reading STI Here K 1 and K 2 are two constants for particular spindle, which can be calculated at any speed from the known geometry of the spindle and the spring constant. All the suspensions were prepared in a 1000 ml beaker. Mixture was well stirred in an electric blender with a perforated socket at the bottom and rotated at 4000 rpm. The time of mixing was 30 min in all the cases. Now suspension was taken in a 400 cm long beaker and placed in the Brookfield thermostat bath maintained at constant temperature (30±1 C). The spindle without guard leg was immersed in the suspension up to the groove. Measurements were taken from the lowest speed of the spindle after one complete rotation of the scale and two complete rotations for highest speed. Determination of Sedimentation Volume (SV) A definite amount of BSS was poured in a 25 ml graduated cylinder with glass stopper. The cylinder was kept at a constant temperature (25±2 C) chamber for 120 h. After this, the volume of sediment was measured from the graduated scale of cylinder. Adsorption of NaCMC Adsorption of NaCMC on BSS was measured by colorimetric method; under which hydrolysis of NaCMC in concentrated sulphuric acid produces glycolic acid that gives colour reaction with added dye. The dye solution was prepared by dissolving 2, 7, napthalene diol (100 mg) in concentrated sulphuric acid (200 ml) and the solution was kept for 8 h inside a refrigerator. From a previously prepared stock NaCMC solution of known ph and ionic strength, NaCMC solutions of different concentrations were prepared in several standard joint bottles. In each bottle, accurately weighed barium sulphate was added and the bottle was shaken in an electric shaker for 24 h at a constant temperature (25 ± 2 C). The particles were then allowed to settle for 5 h. The supernatant solution was taken out with a syringe. To NaCMC (1 ml) solution, colouring dye (9 ml) solution was added. The solution was boiled for 90 min in a water bath and cooled rapidly in an ice bath. After 40 min, reading was taken on a Klett- Summerson photoelectric colorimeter using a red filter. For each experiment, a standard curve was plotted with the values of Klett reading for known concentrations of NaCMC solutions. From the initial and final concentrations of NaCMC solution and the known weight of BaSO 4 added, the amount of NaCMC adsorbed (Γ p ) in mg/m 2 of BaSO 4 was calculated. X-ray Photography X-ray photograph of a rabbit was taken after overnight fasting in a Simens 500 MA X-ray machine having 12 MS and 40 KV capacity. The rabbit was kept in supine position and BSS was fed to the rabbit through a narrow polythene tube. After rolling the rabbit few times sky grams were taken at different time intervals. Results and Discussion The characterization of BSS by STI is based on the validity of the power law Dial reading = K (rpm) n where K and n are constants. Equation demands the linear relationship between log (dial reading) against

3 270 J SCI IND RES VOL 64 APRIL 2005 Fig. 1 Plot of log [Apparent viscosity (cp)] vs log [Shear rate (sec -1 ) for 50% (w/v) BaS0 4 suspension in presence of various concentrations of NaCMC:, 50 % (w/v) BaS0 4 ;, 0.1 % NaCMc; 50 % (w/v) BaSO % NaCMC;, 50 % (w/v) BaS % NaCMC;, 50 % (w/v) BaSO % NaCMC Fig. 2 Plot of Γ p mg vs of NaCMC vs C p at ph 6.6 and different temperature:, 10 C; Δ, 25 C; Ο, 50 C Fig. 3 Plot of Sedimentation volume (ml) vs percent concentration of additives in 50% (w/v) BaSO 4 : , 50% (w/v) BaSO 4 ;, 50% (w/v) BaSO 4 + NaCMc (left upper scale);, 50 % (w/v) BaSO 4 + different percent of Bentonite; Δ, 50% (w/v) BaSO 4 + different percent of PVP log (rpm). In all cases, the graphs are straight lines that show validity of power law. Now 50% (w/v) BSS without any food additive showed pseudoplastic character (Fig. 1) and so also the 0.1% NaCMC solution. The apparent viscosity of 50% BSS mixed with 0.1% NaCMC at any shear rate was intermediate between corresponding pure BSS and pure 0.1% NaCMC solution respectively. The flow was still non- Newtonian. At 0.2% NaCMC, STI value became approx equal to unity thus indicating Newtonian flow of BSS. At 0.3% NaCMC also the viscosity increased but the flow was still Newtonian. Above 0.3% NaCMC, the flow of BSS was again pseudoplastic. The decrease of viscosity of pure BSS by addition of NaCMC solution may be due to NaCMC molecule may take part in the adsorption process, and minimum viscosity of the suspension at 0.2% NaCMC is due to covering of the entire surface of BSS by NaCMC molecules. Further increase of the apparent viscosity above 0.2% NaCMC may be due to the presence of excess NaCMC molecules in the suspension (Fig. 2). The value of Γ p increased as the equilibrium concentration of NaCMC increased. For a high value of NaCMC concentration, Γ p reached maximum value and was insensitive to further increase of C p. The maximum Γ p was close to 0.5 mg of NaCMC per m 2 of BaSO 4 at ph 6.6 and temperature 25 C. The surface area of BSS, determined by palmitic acid adsorption method, was found to be 8.0 m 2 /g powder. So, Γ m p for one g of BaSO 4 will be 4.0 mg. For 50% (w/v) BSS, NaCMC required theoretically for surface coverage will be 200 mg. This coincides well with 0.2% NaCMC, at which the viscosity was minimum and the flow was Newtonian. But with addition of bentonite or PVP (1% or more) in the system, a gradual increase of the apparent viscosity than that of pure BSS was observed. In all concentrations, STI values indicate that the suspensions possess non- Newtonian flow. High sedimentation volume (SV, 19.0 ml) was found in the case of pure BaSO 4 but with the addition of NaCMC, the SV initially decreased and became minimum (Fig. 3). It increased again with further increase of NaCMC concentration. At 0.2% or higher NaCMC, the SV ultimately became constant. There was a minimum viscosity at 0.2% NaCMC concentration. Above this concentration, the apparent viscosity of the suspension increased. The maximum adsorption (Γ p ) at 0.2% NaCMC concentration was 0.5 mg of NaCMC per m 2 of BaSO 4. The maximum

4 NAG: STABILITY AND FLOW BEHAVIOUR OF BARIUM SULPHATE SUSPENSION 271 Fig. 4 Plot of sedimentation volume (ml) vs ph of 50% (w/v) BaSO 4 suspension mixed with different additives:, 50% (w/v) BaSO 4 ; Ο, 50% (w/v) BaSO % NaCMC; Ο, 50% (w/v) BaSO % NaCMC+4% trisodium citrate Fig. 5 Composition of the suspension: BaSO 4, Ο, 50% (w/v); NaCMC, 0.2%; and, trisodium citrate, 4% Radiologist opinion: (Dr K N Jalan, Calcutta Medical Hospital): Stomach shows airy good contrast after barium meal experiment. Skygram (90 min interval) shows good contrast of barium in the mucous membrane intestine and delayed Skygram shows large gut with good contrast SV was observed at 0.2% NaCMC concentration. The entire surface of BSS was well covered at 0.2% of NaCMC, as a result of which the minimum viscosity was attained. At lower concentration of NaCMC, adsorption of polymeric molecules 6,7 may be understood in terms of "bridging model". A polymer molecule bridges several BaSO 4 particles. So, at low concentration of NaCMC, the stability of BSS was greatly reduced, manifested by the low SV compared to that of pure BSS. Addition of bentonite showed slight change in the SV than that of pure barium sulphate, whereas with PVP there was no change of SV. The addition of PVP and bentonite has no significant effect on the sedimentation behaviour of BSS. Therefore, PVP or benotonite did not seem to take part on the adsorption process on the surface of BSS. The mixture of barium sulphate and NaCMC (0.2%) showed the lowest viscosity for the suspension compared to the mixture of NaCMC (0.2%) and PVP (2%) or NaCMC (0.2%) and bentonite (2%) at any particular shear rate (ph 6.8). Now the SV of BSS with NaCMC at different ph was measured by keeping temperature constant (25±2 C) for 120 h. At ph 2.0 and below, BSS with NaCMC (0.2%) showed the SV same as that of pure BSS (Fig. 4). The suspension was stable above ph 5.5, at which the suspension did not sediment within 120 h. From X- ray study of barium meal to rabbit, the above suspension showed poor contrast of the stomach. The skygram of the small intestine was also poor due to the instability of the suspension in the acidic ph of the stomach. To increase the stability of above suspension in acidic region, the suspension was mixed with trisodium citrate. If the ph of BSS was decreased below ph 5.0 in the presence of NaCMC, the SV of the suspension decreased whereas the viscosity of suspension increased. But with the addition of trisodium citrate, the apparent viscosity of the suspension decreased to a considerable extent. At ph 4.8, the apparent viscosity of 50% (w/v) BSS mixed with 0.2% NaCMC is 3.2 cp (at 60 rpm). On addition of trisodium citrate to this mixture (ph 4.8), the apparent viscosity reduces to 2.5 cp (at 60 rpm). The probable explanation is that on addition of trisodium citrate, the dissociation of NaCMC was suppressed and the molecule existed in less expanded form thus causing low viscosity. X-ray picture of rabbit (Fig. 5), using this suspension showed good contrast of the stomach as well as of the small intestine region. Further, the SV of suspension was highly increased at lower ph and the suspension did not sediment within 120 h at ph 4.8. The study indicates that X-ray picture with 50% BSS mixed with NaCMC (0.2%) and trisodium citrate (4%) showed good contrast in acidic and alkaline regions of the gastrointestinal tract. This observation may be useful for the preparation of stable barium meal for radiological and fluoroscopic survey of gastrointestinal tract using indigenously prepared barium sulphate. Conclusions A new radio opaque BSS was devolved by NaCMC and trisodium citrate, which gave good contrast both in acidic and alkaline region for fluoroscopic survey of gastrointestinal tracts.

5 272 J SCI IND RES VOL 64 APRIL 2005 Acknowledgements Author is grateful to Prof D K Chattoraj and Prof B K Sadhukhan, Department of Food Technology, Jadavpur University, Kolkata for their suggestions during experiment, and thankful to Dr K N Jalan, Kolkata Hospital, for clinical trial of BSS. References 1 Miller R E, Diagnosis of gastric and duodenal ulcer by Barium meal, Radiology, 117 (1977) Schwarta S F, Fishwer H W & Houser A E S, Studies of gastric carcinoma and ampullary carcinoma by air contract studies with Barium sulphate, Radiology, 112 (1974) O Reilly, G V A & Boyan G, X-ray studies of small intestinal mal absorption states and carcinoma of the colon by Barium enama method, Br J Radiology, 47 (1974) Nolmym H, Particle size characteristics on the stability of Barium sulphate suspension, Nippon Igaka Hoshaman Saski, 30 (1975 ) Nag A, Sadhukhan B K & Chattoraj D K, Negative adsorption of inorganic salts, sucrose and urea at solid liquid interface, Colloids Surfaces, 23 (1987) 23, Rosen M R, A rheogram template for power law fluids: Technique for characterizing for rheological properties, J Colloid Interface Sci, 36 (1971) Tanford C, Physical Chemistry of Macromolecules (John Wiley, New York) 1964, Napper P H, Flocculation studies of sterically stabilized suspension, J Colloid Interface Sci, 32 (1970)

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