INTRODUCTION:

The pharmaceutical industry faces challenges in developing new active molecule formulations using latest formulation technologies to reduce costs and time required for drug development. Increasing attention is focused on optimizing dosage regimens for active pharmaceutical ingredients (API). Oral drug delivery systems are still considered suitable for administering therapeutic agents, but conventional systems only allow a certain amount of API levels in plasma. Modified release formulations aim to achieve maximum bioavailability and reduce dosing frequency of dosage forms. To increase therapeutic efficacy, lessen adverse effects, and save expenses associated with treatment, site-specific or targeted drug delivery systems are created^1-5.

Colon-targeted drug delivery systems (CTDS)

The biology, pharmacokinetics, and physiology of the organs, cells, compartments and functional proteins involved in drug absorption in the gastro intestine (GIT) have been better understood during the past 70 years thanks to studies in oral drug administration. Colon targeted drug delivery systems (CTDS) have grown in popularity recently with the goal of overcoming the main challenges to colonic drug delivery, such as the absorption and metabolic pathways of the small intestine and stomach. The treatment of diseased states of the colon, as well as conditions including asthma, angina, and rheumatoid arthritis, can all benefit from colon targeting^6-10.

Colon delivery offers several preferential benefits, including being the entrance for drugs to enter the systemic circulation, containing fewer digestive enzymes, ensuring efficient treatment at a lesser dose with minimal side effects, and facilitating chronotherapy in cases of asthma and rheumatoid arthritis. Inflammatory bowel illnesses (IBD) of the colon, such as Crohn's disease and ulcerative colitis, are now being treated locally more frequently^11-14.

CTDS provides therapeutic advantages over conventional oral dosage forms, such as minimizing adverse effects, improving efficacy, producing a well-disposed environment for peptides and proteins, reducing the first-pass metabolism of steroids, and avoiding Non-steroidal anti-inflammatory medications that induce stomach irritation. However, CTDS must overcome limitations such as difficulty in accessing the colon, low water content, and a little amount of drugs can pass the blood-mucosa barrier^15-17.

Anatomy and Physiology of Colon:

In order to avoid absorption from other parts of the GIT, endure little degradation in the upper GIT, and maintain a quantitatively regulated rate of colonic drug release, the fundamental goal of drug delivery to the colon is to prevent absorption from other parts of the GIT. For effective colon targeting, it is essential to comprehend the GIT's composition and operation¹⁸.

Colon pH: The gastrointestinal system has a significant pH gradient, with large gradients between saliva and gastric juice and small gradients across other intestine sections. Diet, illness, and food consumption all have an impact on this pH. Drugs are directed to the colon using the difference in pH between the stomach and small intestine, while the pH drops because of bacterial fermentation of polysaccharides¹⁹.

With more than 500 distinct types of enzymes energising symbiotic anaerobes, the colon's microbial flora predominantly derives from the gut microflora. These enzymes cause medication release from formulations by breaking the links between inert carriers and active ingredients and degrading polymeric coverings. Due to the slow passage of contents, the cecum is the favoured area for microbial colonisation¹⁹.

Whether the individual is fed or fasting, as well as the physicochemical characteristics of the dose form, affect the transport time to the colon. When not fasting, the transit time to the colon is between 3 and 5 hours whereas it is between five and seven hours when not. Diseases that influence colonic transit (18) hamper the typical transit time.

Absorption of drugs from the colon is mainly through trans-cellular transport, with lipophilic drugs absorbing mainly through their ability to permeate through cells. Hydrophilic drugs are absorbed through para-cellular transport via tight junctions between cells. Some drugs with good absorption in the colon include diclofenac, metoprolol, and theophylline, while buflomedel, furosemide, and ciprofloxacin have poor absorption¹⁸.

Colonic formulations: The Background:

Colonic formulations often come in delayed release dose forms that are intended to deliver a burst or continuous release in the colon area. The ideal formulation strategy should take into account the pathophysiology of the colon, the physiological makeup of the colon for systemic action, the physiochemical characteristics of the drug molecule, and the drug molecule's intended release pattern^{18, 20}.

Drug molecules required to be delivered to the colon include those used for treating IBD, colonic cancer, protease and peptide drugs, infectious diseases, rheumatoid arthritis, nocturnal asthma, and angina.

Formulation Technologies for CTDS:

Formulations that aim to target the colon are divided into four groups: prodrug approach ormechanisms that are influenced by time (timed release), pH (delayed release), and microbes (microbial triggered)⁽²¹⁾. Prodrug approaches involve covalent linking of the drug molecule and a carrier moiety to form a prodrug that is stable in the upper gastrointestinal tract (GIT) However, during enzymatic cleavage/hydrolysis, the drug is released in the colon because of the bacteria environment of the colon. These systems are essential for stable drug absorption and are metabolized into lipophilic drug molecules for colonic absorption²².

PH-dependent systems: require pH-sensitive polymers to coat dosage forms, ensuring delayed release and shielding from gastrointestinal fluids. Common polymers include meth acrylic acid and cellulosic derivatives, which can withstand acidic to neutral pH environments for extended periods. Eudragit S100 and L100 are preferred for colonic formulations. However, these systems have limitations, such as inconsistent dissolution, potential factors like short-chain fatty acids, fermentation products, and disease states altering colonic pH.

Time-dependent systems: deliver the drug at predetermined times and at a specific site, such as the colon, in a precise quantity. The effectiveness of these systems depends on the nature of the polymeric material used for formulation.

Microbial-triggered systems: involve microbial enzymatic degradation of polymers in dosage forms to release drugs in the colon. The efficacy depends on the polymeric material used. Alternative methods for colon-specific medication delivery including redox-sensitive polymers, bio adhesion, micro particle coating, and osmotically controlled delivery systems.

Types of formulations for CTDS:

Clinical drug delivery systems (CTDS) are classified into single unit and multiparticulate systems. Single unit CTDS has a disadvantage of potential disintegration due to manufacturing deficiencies or unusual gastric physiology, while multiparticulate CTDS offers increased bioavailability, predictable gastric emptying, and reduced risk of local irritation and systemic toxicity.

In vitro and In vivo Evaluation methods:

In-vitro evaluation methods for CTDS include testing in different buffer solutions, adding colonic bacterial strains, fermenters, and rat fecal mass. In-vivo methods for evaluation include string techniques, endoscope techniques, radio telemetry, roentgenography, and gamma scintigraphy.

Probiotic assisted colonic drug delivery:

The probiotic approach targets colons by combining probiotic strain, microbialdigestible carrier, and triggering temperature. These strains, like bifid bacterium and Lactobacillus, digest the carrier at body temperature, releasing drugs at desired locations. This approach has proven successful in colon drug delivery systems^23-26.

MATERIALS AND METHODS:

Materials:

Aceclofenac was obtained as gift sample from Mylan Pharmaceutical, Hyderabad, India. Guar gum was procured from Loba. Chemicals. Mumbai, India. Xanthan gum was obtained as gift sample from Rajesh Chemicals, Mumbai, India. Sodium starch glycolate, magnesium stearate, microcrystalline cellulose, talc were purchased from S.D. Fine Chemicals, Mumbai, India. All chemicals used in the experiment were of analytical grade.

Preformulation studies:

Prior to adding a medicine into the formulation development process, preformulation studies are a crucial technique for determining the physical and chemical characteristics of the drug.

a) Physicochemical properties of Aceclofenac:

With the use of the sense organs, the acquired drug sample's colour, odour, and taste were assessed. Different solvents, including water, HCl, ethanol, and acetone, were used to measure solubility. To establish the identification of the medicine, acquiring the aceclofenac sample's FT-IR spectrum, examining it for any discernible peaks, and comparing it to reference spectra in databases were done. The open capillary technique was used to obtain the melting point, which is uncorrected. The melting point device was equipped with a fusion tube that contained a tiny amount of powder. The apparatus's temperature was steadily raised, and the temperatures at which the powder began to melt and at which it completely melted were noted.

b) Determination of λ_max:

5 mg of aceclofenac, which had been carefully measured, were dissolved in acetone, 5 mL the volume of the liquid was raised to 100 mL by adding PBS pH 7.4. The volume of this stock solution was then adjusted with PBS pH 7.4 to the required concentration before being pipetted into a 10 mL volumetric flask. Using a UV spectrophotometer, the final product was scanned from 200 to 400 nm. There was found to be a maximum at 265 nm.The solution was rescanned after 3 days of room-temperature storage, and no changes were seen.

c) Preparation of Calibration Curve in PBS pH 7.4:

A 25 mL volumetric flask was filled with accurately weighed 25 mg of aceclofenac, which was then dissolved in PBS pH 7.4 and the volume was adjusted to the correct concentration using PBS pH 7.4. The result was a stock solution with 1000 g/mL. A further 100 mL volumetric container was filled with PBS pH 7.4 to the mark after 10 mL of the aforementioned stock solution were collected, increasing the volume and bringing the solution's concentration to 100 g/mL. The sample was then examined using a UV spectrophotometer using aliquots of the stock solution, ranging in size from one to 10 mL from the aforementioned solution, at a maximum wavelength of 265 nm. Plotting of the standard curve between concentration and absorbance²⁷.

In vitro digestion of guar gum by probiotics:

A guar gum slurry (1% w/v) was made by dissolving 2g of guar gum in 200 mL of distilled water. Slurry was mixed with contents of one Vibact capsule and one Vizylac Rich capsule, and the combination was kept in an incubator at 37 °C for 24 hours. Each dispersion's pH and viscosity fluctuations were monitored over time using calibrated pH metres from Labtronics and Brookfield viscometers, respectively. One% w/v of guar gum dispersion served as the control sample for the study^28-31.

Formulation of matrix tablet of Aceclofenac:

Using guar gum:

According to Ghosh et al. (2010), moist granulation was used to create the guar gum matrix tablets. Each of the following substances—lactose, guar gum, magnesium stearate and talc was processed through number 60 sieve separately to get particles of the same size. Weighed quantity of Aceclofenac was sifted through sieve number 100.

Aceclofenac, lactose and guar gum was mixed together and blended with addition of water (q.s) for granulation. The damp mixture was run through a 14-hole sieve prior to being dried for two hours at 50°C in a tray drier. Filter number 16 was applied to the dried granules, which generated a mixture of granules and fines. A double cone blender with talc and magnesium stearate was used to mix the granules for five minutes. To compress the lubricated granules, a single punch tablet press was employed. Table 1 presents the composition of Aceclofenac tablets.

Table 1. Composition of matrix tablets

	Quantity of each ingredient per tablet in mg
Ingredient	MT1	MT2	MT3	MT4	MT5
Aceclofenac	100	100	100	100	100
Guar Gum	100	200	200	200	200
Lactose	285	185	105	85	65
Magnesium Stearate	5	5	5	5	5
Talc	10	10	10	10	10
Vibact	-	-	40	50	60
Vizylac Rich	-	-	40	50	60
Weigh of tablets	500	500	500	500	500

Using guar gum-probiotic combination:

Guar gum, which makes about 40% of the weight of the Aceclofenac matrix tablets, was used in the preparation process. Before granulation, half of the probiotics were added, and the other half was added before the mixture was finally blended. Table 1 presents the composition of Aceclofenac tablets.

Evaluation of Formulations:

Rheological Properties of the granules:

a. Angle of repose:

To get the angle of repose, we applied funnel approach. Microspheres were placed into a funnel and accurately weighed. The funnel was raised to a height where the tip just touches the pile at the bottom. On reaching the surface, the granules were permitted to freely pass via the funnel. The formula was used to calculate the angle of repose after measuring the diameter of the powder cone³².

b. Bulk Density (BD):

Weighing precisely 10 g of the microspheres and transferring it to a graduated cylinder containing 100 mL allowed us to calculate the apparent bulk density (ρb). Using the volume that the microspheres occupied as a starting point, the bulk density formula was utilised to estimate the bulk density³².

c. Tapped Density (TD):

After tapping the measuring cylinder for a certain amount of time, the blend's volume within was measured.The measuring cylinder contained microspheres of mass that is known. Using the formula of tapped density, ρt was determined³².

d. Percent compressibility (Carr’s Index):

The consolidation index (Carr’s compressibility index) was determined by comparing the BDand TD of the powder. Using the standard formula, Carr's compressibility index is determined. According to Carr's Index, a score below 15% denotes favourable flow characteristics, whereas a value above 25% denotes unfavourable flow characteristics³².

e. Hausner’s Ratio:

Utilising the standard formula, Hausner's ratio was determined from BD and TD.

Evaluation of the matrix tablets:

a. Thickness:

A digital Vernier calliper was used to gauge the thickness of 20 randomly chosen from tablets of each batch of formulation.

b. Weight variation test:

To determine the average tablet weight, 20 randomly selected tablets were weighed. Following the individual weighing of each of these tablets, the deviation from us determined the average weight. The percent weight difference was utilised to compute the variation in weight from the average³³.

c. Friability test:

Using a friability test apparatus of the Roche type, the formulations' friability was assessed. Twenty tablets were weighted (W_initial) initially before being added to the friabilator. For 4 minutes at 25 rpm, the friabilator was spun up to 100 times per minute. The tablets received a final weight (W_final). The approach was then applied to determine the percentage of friability³³.

d. Hardness test:

The strength of formulation of the tablets was assessed using a Monsanto-style hardness tester. Using a hardness tester, the amount of force needed to break three randomly chosen tablets from each batch of the formulation was recorded³³.

e. Drug content:

The average weight was determined using the weight of 20 tablets made with each formulation. With the use of a mortar and pestle, the tablets were reduced to a fine powder. Then, 25 mg of the pharmaceutical powder was added to 25 ml of PBS pH 7.4. This stock solution was then diluted by 10 mL to a final volume of 100 ml using PBS pH 7.4. 20 g/mL was achieved by pipetting 2 mL of this stock solution and diluting it by 10 ml. A calibration curve was developed to detect the solution absorbance at 265 nm with a UV spectrophotometer and to calculate the concentration. The dilution factor was used to compute the medication content³³.

f. In vitro release studies in absence of rat caecal content:

All matrix tablet formulations underwent in vitro dissolution testing employing Apparatus 1, Basket type, 37°C, and 100 rpm for the USP dissolution test and phosphate buffer pH7.4 as the dissolving media (200 mL). After the pill was put in the basket, the examination into pill breakdown was conducted for 12 hours. After pipetting off 1 mL of the dissolving media at regular intervals, it was diluted to a level of 10 mL in PBS pH 7.4. A UV visible spectrophotometer was used to test the solution's absorbance at 265 nm. After each withdrawal, 1 mL of fresh media was added to the dissolving flask³³.

g. In vitro release studies in presence of rat caecal content:

The release investigation was carried out in presence of rat caecal material to determine how susceptible guar gum is to being affected by the colon's microbial flora.

Preparation of rat caecal content:

Every animal study was authorized by the IAEC. To collect the caecal contents, Wistar rats weighing 150–200 g were given a standard meal and 4 mL of 1% w/v Guar gum dispersion in water each day for seven days. Three rats were strangulated to death 30 minutes prior the commencement of the medication release trials. After their abdomens were opened, their internal organs were immediately moved to 6.8 pH phosphate buffer that had already bubbled with CO2. To achieve the requisite concentration of 4% weight/volume of caecal material, the caecal bags were opened, their contents were individually quantified, homogenised, and suspended in phosphate buffer at pH 6.8³².

h. In vitro dissolution studies:

200 mL of phosphate buffer with a pH of 7.4 and rat caecal content (4% w/v) were used to measure the drug release for all formulations. PBS pH 7.4 was used to dilute 1 mL of the dissolving media at regular intervals to a volume of 10 mL. The absorbance at 265 nm of the solution was measured with a UV visible spectrophotometer. Each time a sample was removed, 1 mL of new media was added to the dissolving flask. The trial was extended for a second day.

RESULT AND DISCUSSION:

The physical description of the aceclofenac drug was carried out in accordance with the described process, and the outcomes were evaluated in comparison to the requirements. It turned out to be a white odourless powder, bitter in taste, 149-153°C mp with different solubility fractions in different solvents (water insoluble, ethanol soluble, HCl partially soluble, acetone freely soluble).

Aceclofenac drug sample's IR spectrum was obtained using a Bruker FTIR spectrometer, and the peak heights were compared to reference spectra from spectrabase.com (Table 2, Figure 1a, and 1b). The drug sample's physical attributes were assessed, and its authenticity was verified by contrasting its FTIR spectra with reference spectra taken from a database. The peaks of C=O (1770), N-H bend (1580), C-H stretch (1458), C-N stretch (1307), and C-O stretch (1280) were observed in the FTIR spectrum. All of the peaks could similarly be visualised in the Aceclofenac reference spectrum.

Table 2. Vibration frequencies (FTIR) of Aceclofenac

S. No	Wave number (Standard)	Occurs due to	Wave number (Sample)
1	3320	O-H stretching	3318
2	1760	C=O stretching	1770
3	1710	C=O stretching	1606
4	1590	N-H bending	1580
5	1480	C-H stretching	1458
6	1370	Aromatic C=C stretching	1344
7	1420	C-H bending	1417
8	1325	C-N stretching	1307
9	1275	C-O, C-N stretching	1280
10	1230	C-N stretching (aromatic amine)	1243

The absorption maximum of Aceclofenac in PBS pH 7.4 was found to be 337 nm (Table 3, Figure 2 and 3). A calibration curve was prepared over 10-100 µg/mL concentration range. The analysis of in vitro digestion of guar gum in company of probiotics were out to evaluate the impact of the gut microbial flora of guar gum. The pH and viscosity of guar gum 1% w/v solution was used as marker for degradation of guar gum. The results obtained are presented in Table 4.

Table 3. Absorbance of Aceclofenac in PBS pH 7.4

S. No	Concentration (µg/mL)	Absorbance
1	10	0.071
2	20	0.133
3	30	0.193
4	40	0.255
5	50	0.317
6	60	0.381
7	70	0.459
8	80	0.527
9	90	0.598
10	100	0.672

Figure 2. UV spectra of Aceclofenac

Figure 3. Standard curve of Aceclofenac

All of the granular formulations displayed satisfactory flow characteristics, with angles of repose ranging from 25°71' to 27°41'. The outstanding rheological properties of all the formulations were indicated by the fact that none of them had an angle of repose greater than 40°. It was discovered that the BD fluctuated from 0.42 to 0.46 g/cm³ and the TD vacillated from 0.50 to 0.54 g/cm³.

One technique for figuring out the powder flow characteristics is the Carr's index of compressibility. The data on bulk and tapped density are used to calculate it. All of the formulations' Carr's indices fell within the range of 13.72 to 17.30%, showing good flow ability (Table 5). A percentage compressibility rating of less than 20 indicates that the powder has excellent flow characteristics. The formulas' Hausner's ratio was observed between 1.159 and 1.209. Good flow qualities are indicated by a ratio of less than 1.25 (Table 5).

Table 5. Rheological parameters of various granular blends

Batch Code	Angle of repose	Bulk Density	Tapped Density	Hausner’s Ratio	Carr’s Index
MT1	25°71’	0.43	0.52	1.2093	17.3077
MT2	27°37’	0.42	0.5	1.19048	16
MT3	27°41’	0.44	0.51	1.15909	13.7255
MT4	26°38’	0.46	0.54	1.17391	14.8148
MT5	27°10’	0.43	0.53	1.23256	18.8679

According to the precompression parameters, the granular mixes made with various excipient ratios will not cause any issues during compression. The thickness, hardness, weight variation, medication content, and friability of the compressed tablets made from each granular blend were assessed (Table 7). Since all of the criteria were determined to be within pharmacopoeial limitations, the findings of these examinations revealed good quality in the tablets.

Table 6. Characteristics of the matrix tablet formulations

Batch Code	Thickness (cm)	Hardness (Kg/cm²)	Weight variation (%)	Friability (%)	Drug Content (%)
MT1	0.5	5.5	0.270	±0.39	98.1
MT2	0.5	5.6	0.270	±0.34	98.6
MT3	0.5	5.5	0.270	±0.31	99.3
MT4	0.5	5.4	0.270	±0.35	98.5
MT5	0.5	5.5	0.270	±0.34	98.2

The in vitro discharge summary of all formulations was evaluated both with and without rat caecal material in the dissolving media (PBS pH 7.4). It was discovered that the other formulations released 80–99% of the medicine over the course of 24 hours; however, the 20% guar gum formulation (MT1) released just 69% of the drug in the absence of the caecal medium. Additionally, it was shown that raising the probiotic content was able to improve the drug release from the formulations, pointing to the probiotic's potential assistance in the colonic microflora's ability to break down guar gum. The release study in absence and presence of rat caecal content was done for all tablet formulations and the result is presented in Table 8 and 9 while the release profile is represented in Figure 4 and Figure 5 respectively.

Figure 4. Cumulative percent of Aceclofenac released from matrix tablets in absence of rat caecal content

Figure 5. Cumulative percent of Aceclofenac released from matrix tablets in presence of rat caecal content

Table 7. In vitro release profile of formulations in absence of rat caecal content

Time (h)	% Cumulative release
Time (h)	MT1	MT2	MT3	MT4	MT5
0.00	0.00	0.00	0.00	0.00	0.00
1.00	4.81	6.48	9.01	8.28	8.41
2.00	14.82	16.88	22.69	18.35	20.22
4.00	17.88	23.49	34.83	32.43	31.76
6.00	22.62	31.63	41.03	38.96	38.30
8.00	29.49	37.23	48.57	45.50	44.63
10.00	35.36	43.36	56.77	53.17	50.77
12.00	41.03	48.37	60.84	58.37	57.31
16.00	45.03	60.64	73.85	71.18	64.24
20.00	55.50	70.18	88.79	84.45	76.85
24.00	69.31	85.19	99.73	94.46	91.66

Table 8. In vitro release profile of formulations in presence of rat caecal content

Time (h)	% cumulative release
	MT1	MT2	MT3	MT4	MT5
0.00	0.00	0.00	0.00	0.000	0.000
1.00	6.43	6.43	6.43	6.43	6.43
2.00	18.24	21.98	19.11	17.17	18.97
4.00	23.38	29.85	37.85	32.71	31.91
6.00	28.18	32.85	46.85	42.52	38.85
8.00	34.45	39.79	54.59	53.46	46.32
10.00	39.85	45.59	61.99	73.04	58.93
12.00	51.66	57.00	79.20	92.28	69.66
16.00	68.13	66.07	99.81	97.14	85.34
20.00	78.27	82.48	-	-	91.61
24.00	85.21	96.28	-	-	98.950

In the presence of rat caecal material, the drug release increased in all formulations. It was discovered that the probiotic's impact on guar gum degradation was time-dependent, and after 8 hours of dissolution research, a statistically significant increase in drug release was seen. This was consistent with the digesting study, which revealed that the microflora's interaction with guar gum results in its de-polymerization and enhances medication release after around 8 hours

CONCLUSION:

The angle of repose was reported in between 25°71' and 27°71'. The BD varied between 0.42 and 0.46 g/cm3, while the TD ranged between 0.50 and 0.54 g/cm3. The Carr's Index of the granules observed in this study was found to range from 13.72 to 18.86%, and the Hausner's ratio was found to range from 1.159 to 1.204.

All of the tablets were 5 mm thick, and their hardness values ranged from 5.4 to 5.6 kg/cm². Each tablet's drug concentration ranged from 98.1 to 99.3%, while its friability and weight variation were also found to be between 0.31 and 0.35 percent. The in vitro drug release from matrix tablets was examined in both the absence and presence of rat caecal content, and it was observed that probiotics had an impact on the release of the medication from the tablets. The drug release from all of the formulations could be increased by the rat caecal content. The formulation MT3 had the maximum cumulative drug release of 99.73% and 99.81% in the presence and absence of rat caecal material, respectively.

Probiotics were used as targeting aids and guar gum was used as the polymeric matrix in the preparation of the Aceclofenac-loaded colon specific matrix tablets in the current investigation. The results revealed that this technology was able to achieve sustained drug release from the formulations as well as colonic release of the bulk of the drug even in the absence of colonic bacteria.

In light of the foregoing, it can be said that the matrix tablets created using the probiotic-assisted procedure are an excellent delivery system with good release behavior for actively releasing drug in the colon. As a result, this system would provide a secure and efficient method for treating stomach ulcers or other diseases of the gut.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGEMENT:

We are very thankful to the IES Institute of Pharmacy and Zodprobe Scientific for providing the necessary facilities to carry out this research work. Their support and resources were invaluable in the successful completion of our study.

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Received on 20.02.2024 Revised on 10.06.2024

Accepted on 15.09.2024 Published on 24.12.2024

Available online from December 27, 2024

Research J. Pharmacy and Technology. 2024;17(12):5790-5798.

DOI: 10.52711/0974-360X.2024.00880

Time (h)	Guar Gum		Guar Gum + Vibact		Guar Gum + Vizylac Rich
Time (h)	pH	Viscosity (cps)	pH	Viscosity (cps)	pH	Viscosity (cps)
0	6.98	2560	6.98	2560	6.97	2560
1	6.99	2560	6.98	2560	6.97	2560
2	6.98	2560	6.97	2560	6.98	2560
4	6.97	2560	6.97	2560	6.98	2560
6	6.99	2560	6.98	2560	6.98	2560
8	6.98	2560	6.98	2560	6.97	2560
10	6.97	2560	6.83	2340	6.75	2390
14	6.98	2560	5.91	2240	5.90	2210
18	6.97	2560	5.70	1830	5.75	1870
24	6.96	2560	5.43	690	5.51	810