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R. Kamboj et al. Journal of Medicinal and Chemical Sciences Original Article

Journal of Medicinal and Chemical Sciences 2018 (1) 11-17

J. Med. Chem. Sci.

Taste-masking assessment of orally disintegrating tablets of valsartan using ion

exchange resin
Rohit kamboj*, Sweta Kamboj, Ashwani Kumar
Guru Gobind Singh College of Pharmacy, Yamuna Nagar, Haryana (India)

A R T IC LE IN F O A B S TR A C T

Article history: Oral disintegrating tablets are novel attractive dosage form that disintegrate or dissolve in the
Received 10 May 2018 buccal cavity within seconds without use of water. The major drawback in designing of this
Revised 23 May 2018 dosage form is unpleasant taste of active entity. Valsartan isan anti-hypertension drug used in
Accepted 28 May 2018 treatment of high blood pressure, congestive heart failure (CHF) and post-myocardial infarction
Available online 28 May 2018 (MI). It is characterized by its bitter taste which affects the patient’s compliance. The aim of
present research work is taste-masking assessment of orally disintegrating tablets of valsartan
Keywords: using ion exchange resin (indion 254). The drug was characterized according to different
Taste masking compendia methods, on the basis of identification by UV spectroscopy, pH, organoleptic
Orally disintegrating tablet properties and other tests. Drug-Resin compatibility and drug polymer compatibility was carried
Ion exchange resin out by FTIR. The values of pre-compression parameters assessed, were within specified limits and
valsartan showed good free flowing properties. The data obtained of post-compression parameters such as
weight variation, hardness, friability, wetting time, water absorption ratio, content uniformity,
disintegration time and dissolution was found within the prescribed limits. The F10 batch with
disintegration time 20 sec and dissolution 97.46 was selected as optimized formulation. Batch F10
was also subjected to stability studies for three months and was tested for its appearance, average
weight, hardness, disintegration time, percent friability and its release rate which in prescribed
range and satisfactory.

1. Introduction rate of dissolution of the formulation in saliva, rate of absorption

from saliva and overall drug bioavailability and polymers.4
T he term ‘Oral disintegrates tablets’ as give the idea in
European Pharmacopoeia is defined as ‘‘uncovered tablet
for buccal cavity, where it disintegrates before ingestion’’. Oral
Without changing its safety and efficacy, a drug's taste has to
be masked and techniques are being adapted to meet this need,
route of administration is most preferable and suitable route of especially for the pediatric and juveniles patients. These are as
drug administration as it include lots of advantages of this like follows: taste masking with flavors, taste masking by granulation,
ease of administration, patient compliance and accurate dosing. microencapsulation, ion exchange resins, solid dispersion
But there is one drawback of these dosage forms is swallowing method, bitterness inhibitor. When single approach for taste
problem for some patients of all age groups, mainly the elderly masking is not very successful for highly bitter drugs, using
and pediatrics. Mostly new drug entity has poor water solubility combination of various taste masking technologies is found to be
and poor dissolution in GI fluids is a limiting aspect to the in a more efficient strategy.5 Taste masking of the drug employing
vivo bioavailability after oral administration. Fast dissolving drug ion exchange resins (IER) has proved to be safe and effective
delivery is a significant Novel Drug Delivery (NDDS) which method for formulation of various dosage forms.
main purpose to improve solubility, increase efficacy and
In this paper we account Taste-masking assessment of orally
enhance safety of drug entity to formulate a dosage form for
disintegrating tablets of valsartan using ion exchange resin.
administration with better patient compliance. These tablets
Valsartan is an antihypertensive drug commonly used for
display a fast and spontaneous de-aggregation in the mouth, soon
treatment of high blood pressure, congestive heart failure (CHF)
after it comes in contact with saliva, dissolving the active
and post-myocardial infarction (MI). Valsartan suffers for poor
ingredient and allowing absorption through all possible
patient’s acceptability due to its bitter taste, which can be
membrane it comes in contact during deglutition. 1
overcome by taste masking. Taste masking by ion exchange resin
In the recent years, there is several new advanced technologies i.e., Indion 254 was engaged because of its efficacy and superior
have been introduced for the formulation of oral disintegrates ability of taste masking. Ion exchange resins have been gradually
tablets with patients compliance, low disintegration time, taste more used for the taste masking of bitter taste drug and help to
masking ability and sugar free tablets for diabetic patients. 2 prepare oral disintegrates tablets. 6 Ion exchange resins are
These techniques are based on the principles of increasing polymers that are capable of exchanging particular ions within
porosity and/or addition of super-disintegrates and water soluble the polymer with ions in a solution that is passed through them.
excipients in the tablets.3 This ability is also seen in various natural systems such as soils
and living cells. The synthetic resins are used primarily for
The formulations prepared from these techniques differ from purifying water, but also for various other applications including
each other on the basis of the factors like mechanical strength of separating out some elements. They are available in desired size
final product, drug and dosage form stability, mouth feel, taste, ranges.

* Corresponding Author:
E-mail address: [email protected] (R. kamboj) J. Med. Chem. Sci. 2018, 1, 11-17
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R. Kamboj et al. Journal of Medicinal and Chemical Sciences Original Article

Table 1 Formula of different formulations of Valsartan MDTs (mg)

Entry Ingredients (in mg) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10

1 Valsartan 40 40 40 40 40 40 40 40 40 40
2 Resin 30 30 60 60 60 60 60 80 80 80
3 Cross -povidone 6 6 6 8 8 8 10 10 12 12
5 Dry maize starch 18 - - 21 31 30 28 19 20 25
6 Mannitol 60 80 - - - - - - - -
7 MCC(rank 102) 25 40 40 40 25 40 30 27 21
8 Lactose - 25 29 - - - - - - -
9 Aspartame 1 2 1.5 - 1 - 2 1 - -
10 Sodium saccharin 0.5 - 0.5 - - 1 - - - -
11 Neotame - - - 1.5 1 1 0.5 - 0.5 1
12 Flavour 2** 2* 2** 2** 2 2*** 2*** 2*** 2*** 2***
13 Magnsiumsterate 1.5 2 2 1.5 1.5 2 1.5 1.5 1.5 2
14 Aerosil 3 3 3 2 2 2 2 1 2 2
15 Citric acid 3 3 2 2 2.5 2 2 2 2
16 Mono sod.citrate - - 3 2.5 - - - - - -
17 Sodium citrate - - - - - 2.5 2 3 3 3
tribasic dihydrate
* Total 190 190 190 190 190 190 190 190 190 190
Flavor----strawberry, orange**, pineapple***.

Table 2 Evaluation of Precompressed Powder Blend

Entry Bulk density Tapped density Carr’s index Hausner ratio Angle of repose
F1 0.4175 0.4830 14.54 1.17 32.18
F2 0.4278 0.4870 12.s5 1.13 33.57
F3 0.4188 0.4790 12.56 1.14 34.42
F4 0.4388 0.4971 11.72 1.13 31.37
F5 0.4273 0.4907 12.92 1.14 32.29
F6 0.4232 0.4842 12.59 1.14 31.19
F7 0.4188 0.4780 12.34 1.14 31.21
F8 0.4206 0.4750 11.45 1.12 31.09
F9 0.4219 0.4778 11.69 1.13 31.27
F10 0.4246 0.4825 12.11 1.13 32.25

Bitter cationic drugs can get adsorbed on to the weak cationic Batches F8 (39 sec), F9 (33sec) and F10 (20sec) exhibited
exchange resins of carboxylic acid functionally to form the decrease in disintegration time and wetting time (24–26 sec).But
complex which is not bitter. Further Drug-Resin complex can be F10 had shown more decrease in disintegration time and wetting
formulated as lozenges, chewing gum, suspension or dispersible for this reason batch F10 was selected. The tablet blend of all the
tablet and mask the taste.7 batches were evaluated for different derived properties viz. angle
of repose (between 32.18 and 32.25), Bulk density (between 0.41
2. Result and discussion: and 0.42 gm/cm3), Tapped Density (0.483–0.482 gm/cm3),
Compressibility index (between 14 and 12, hausner ratio
The formulation of oral disintegrating tablet was made by using (between 1.17 and 1.13) and flow ability. The results of angle of
valsartan–resin complex. Batches F1– F10was prepared by direct repose and compressibility indicated that the flow ability of blend
compression to select disintegrate, from the results. It can be is significantly good. Oral disintegrating tablets were pre-pared
concluded that the tablets containing crospovidone exhibit quick in batches F1–F10 and evaluated for tablet properties like, weight
disintegration time. From the results it was obvious that the variation, hardness, friability, wetting time, water absorption
optimum concentration of crospovidone might be less than 10%. ratio, content uniformity, disintegration time and dissolution.

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R. Kamboj et al. Journal of Medicinal and Chemical Sciences Original Article

Table 3 Physical evaluation of MDTs Valsartan

Weight Thickness Hardness Friability Wetting time In-vitro disintegration Percent drug
2
Entry Variation (mg) (mm) (kg/cm ) (%) (seconds) time (seconds) content (%)
F1 186-193 2.82 1.8 0.0495 64 58 101
F2 185-192 2.82 1.6 0.0462 75 67 99.50
F3 187-194 2.72 2 0.1126 80 72 98.70
F4 187-192 2.72 2 0.0500 60 50 101
F5 185-192 2.82 1.8 0.3980 56 45 99
F6 188-195 2.84 1.6 0.4960 51 47 98
F7 186-193 2.72 2 0.0500 37 29 98
F8 185-194 2.82 1.8 0.3980 39 30 99
F9 188-195 2.89 2.2 0.431 33 24 99
F10 187-194 2.81 2.3 0.465 26 20 99

Table 4 Dissolution study of different batches

Time(min) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10
15 85.50 84.93 84.90 83.25 83.25 86.27 86.05 82.22 86.26 86.94
30 94.69 95.33 96.67 94.29 94.64 95.66 93.08 94.57 94.72 96.75
45 95.37 96.34 97.03 95.33 95.34 96.01 96.43 95.98 96.07 97.42

Fig 1. Dissolution study of different batches

All the tablets passed weight variation test as the percent The tablets prepared from crospovidone i.e., F1– F10showed a
weight variation was within the pharmacopoeia al limits. drug release between 82.22 and 97.42. Results for hardness,
Hardness were shown in the range of 1.8–2.3 kg/ cm2 in all the disintegration time, dissolution and content uniformity show no
formulations which indicated good mechanical strength with an appreciable change up to 3 months of accelerated stability
ability to withstand physical and mechanical stress conditions studies.
while handling. In all the formulations, the friability value was
less than 1% and meets the official limit. The results of 3. Conclusion:
disintegration of all the tablets were found to be within
prescribed limits and satisfied the criteria of oral disintegrating Great deal of attention is drawn by oral disintegrating tablets in
tablets. The values were found to be in the range of 0.049–0.46. last few years. Because of the increase in the average life extent
The percentage drug content of all the tablets was found to be and the decline, with age, in swallowing ability, oral tablets
between 101 and 99 of valsartan which was within acceptable administration to patients is momentous problem and has become
limit. All the tablets prepared were subjected for release profile.

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R. Kamboj et al. Journal of Medicinal and Chemical Sciences Original Article

the objects of public attention. Dosage forms that can be valsartan were prepared. The absorbance of dilutions was
suspended or dissolved in mouth with water for swallowing measured against pH 6.8 phosphate buffer solutions as a blank at
easily are desired candidate for the geriatric and pediatric 250 nm using UV/visible spectrophotometer. The plot of
population. Organoleptic characteristics like taste and odour are absorbance Vs concentration was plotted and subjected to linear
required features in evaluating the consumer acceptability, regression analysis.
thereby are needed for their success in the market.
4.6. Characterization of drug and excipients
In this article ion exchange resin are used for taste masking of
oral disintegrating tablets which have shown preferred results. In
this present work ten formulations are prepare by complexation 4.6.1. Drug-excipient compatibility studies
with ion exchange resin which resulted in change of crystalline The physiochemical Compatibility of the valsartan with indion
form of drug to amorphous form which has improved the 254, after that combination of the valsartan and super
dissolution properties of valsartan. disintegrates and excipients were carried out to investigate the
changes in chemical composition of the drug after combining it
4. Materials and methods with the excipients.

4.1. Materials The drug-polymer compatibility was studied by FTIR

(Shimadzu IR Affinity-I) spectrophotometry. The mixture of
All materials used in the present research were commercial drug and potassium bromide was ground into a fine powder using
samples. Active agent: Valsartan (Morepen Lab. Ltd), Resin mortar Pestle and then compressed into a KBr discs in a
(Indion 254) (Morepen Lab. Ltd), microcrystalline cellulose hydraulic press at a pressure of 75 Kg/cm2. Each KBr disc was
(Morepen Labs), Crospovidone (Paracol corporation), dry maize scanned 45 times at a resolution of 2 cm–1. The characteristic
starch, mannitol, lactose, aspartame and magnesium stearate peaks were recorded.
(Amishi Chemicals Ahmedabad), aerosol, citric acid, sodium
citrate tribasic dehydrate-2 are gift sample from Morepen Lab. 4.6.2. TLC Method:
Ltd. All other reagents were of analytical grade.
The drug polymer compatibility was also studied by
4.2. Preparation of tablets densitometry TLC evaluation using aluminum foil plates
percolated with silica gel (60G F254) with Ethyl acetate:
The preparation of tablets was carried out after the analysis of chloroform: glacial acetic acid,(8:2:0.2 v/v as mobile phase.
drug samples, ion exchange resins, mixture formation and their
analysis, drug loading studies, formulation and evaluation of 4.6.3. HPLC analysis
Tablets. 8
The quantitative analysis of drugs was performed using an HPLC
4.3. Analysis of Valsartan (Waters 515 series, water corporation, USA), For HPLC, mobile
phase, water: acetonitrile: glacial acetic acid (500:500:01) was
The Valsartan was characterized according to different analytical filtered and degassed. The injection volume was injected 20µl
methods and was found to be white to white crystalline powder with a flow rate of 1.0ml/min. Detection was carried out at 273
with characteristic odour. Found to have a melting point in range nm. At column temperature 250ᵒc and run time set at 10 minutes.
of 116–117 oC and a pH of 4-8, λmax of 250 nm, and all the
findings matched the official reports. 4.7. Preparation of drug–resin complex (DRC)

4.4. Scanning of Valsartan. In batch process, there is different ratio of Drug: Resin (1:0.75,
1:1, 1:1.5, and 1:2), Beaker containing deionized watermix with
The λmax of drug had been determined by subjecting the stock resin and stirred with mechanical stirrer for 30 min accurately
solution (100 mg of valsartan was accurately weighed and weighed of valsartan was added and stirred for 2 hours. The
transferred into a 100 ml volumetric flask. The drug was then mixtures were filtered and residue was washed with deionized
dissolved in 20 ml of methanol and diluted up to the mark with water. DRC was then washed with sufficient quantity of
pH 6.8 phosphate buffer solution) with) to the U.V. scan between deionized water for three times to remove loosely adsorbed drug
200-400 nm. The wavelength for maximum absorbance was from resinate surface. DRC was allowed to dry at room
noted from the scan at 250 nm (because of sharp and intense temperature and was stored in tightly closed container and used
peak) in pH 6.8 phosphate buffer which confirms to the reported in further studies.
value.
4.8. Formulation of oral disintegrating tablets
4.5. Preparation of standard calibration curve using with pH
6.8 phosphate buffer solution Valsartan tablets were prepared according to the formula given in
(Table 1). A total number of ten formulations were prepared. All
A standard curve of valsartan(using 100µg/ml) was obtained by the ingredients were passed through 40 mesh sieve separately and
measuring absorbance of various aliquots at 250 nm.For collected. The ingredients were weighed and mixed in a
thestandard curve, 100 mg of valsartan was accurately weighed geometrical order. All the sifted ingredients were then weighed
and transferred into a 100 ml volumetric flask then 10 ml was individually for each batch using electronic weighing balance.
pipetted out and diluted to 100 ml using pH 6.8 phosphate buffer The weighed ingredients were then transferred to a laboratory
solutions. mixer in a sequential manner. First the treated drug and resin
complex was mixed with micro crystalline cellulose and maize
Different aliquots containing 2, 4, 6, 8, 10, 12 & 14 µg/ ml of starch and then other excipients were added.

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R. Kamboj et al. Journal of Medicinal and Chemical Sciences Original Article

Table 5 Observation of parameters for the stability studies at the accelerated conditions (40⁰C ±2 ⁰ C/75%±5% RH)

Time

Parameters Days 30 Days 60 Days 90 Days

Appearance No change No change No change No change
Average weight 191 191 192 192
2
Hardness (kg/cm ) 2 2 1.8 1.8
Disintegration time(seconds) 20 20 20 20
Percent friability 0.465 0.465 0.465 0.465

Table 6 Release kinetics data of optimized batch (F10 ) after 30, 60 & 90 days

Percent drug release

Entry Time (min) 0 Days 30 Days 60 Days 90 Days
1 15 86.94 84.43 84.20 84.01

2 30 96.75 94.21 93.92 93.62

3 45 97.42 96.03 95.92 95.63

Fig 2. Release kinetics of F10 in stability testing conditions

Talc and magnesium stearate were added few minutes before the
4.9. Evaluation of blend for oral disintegrating tablets
start of compression. The tablet was punched by using 9mm
punches to get a tablet of 190 mg weight. Before tablet
preparation, the powder mixture of all formulation were passed 4.9.1. Angle of repose (θ)
to pre-compression parameter like bulk density, tapped density,
angle of repose, Carr’s index, hausner ratio, and compressibility The friction forces in a loose powder were measured by the angle
and flow ability. The oral disintegrating tablets prepared of repose (θ), an indicative of the flow properties of the powder.
subjected to post-compression parameters like, content It defined as maximum angle possible between the surface of the
uniformity, hardness, friability, weight variation, dissolution and
pile of powder and the horizontal plane
in vitro disintegration. Batches were prepared by direct
compression method. Direct compression is the preferred method
for preparation of tablets. Current usage of the term ‘‘direct
compression’’ is used to define the process by which tablets are
compressed from the powder blends of active ingredient/s and
suitable excipients. No pretreatment of the powder blends by wet
or dry granulation is involved. where, (θ) is the angle of repose, h is the height in cm and r is the
radius in cm.

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R. Kamboj et al. Journal of Medicinal and Chemical Sciences Original Article

The powder mixture was allowed to flow through the funnel The flow characteristics are measured by angle of repose.
fixed to a stand at definite height (h). The angle of repose was Improper flow of powder is due to frictional forces between the
particles. These frictional forces are quantified by angle of
then calculated by measuring the height and radius of the heap of repose. Angle of repose is defined as the maximum angle
powder formed. Care was taken to see that the powder particles possible between the surface of a pile of the powder and the
slip and roll over each other through the sides of the funnel horizontal plane.
(Table 2).

4.9.2. Bulk Density (Db)

It is the ratio of total mass of powder to the bulk volume of

powder. It was measured by pouring the weight powder (passed
4.10. Evaluation of tablets
through standard sieve # 20) into a measuring cylinder and initial
weight was noted. The bulk density was calculated according to The formulated oral disintegrating tablet were evaluated for
the formula mentioned below. It was expressed in g/ml and given different parameters like, weight variation hardness,9 friability,
by wetting time,4 water absorption ratio,10 content uniformity and
dissolution.11

where, M the mass of powder and Vbbulk volume of the powder. 4.10.1. Thickness

The thicknesses of the compressed tablets were measured by

4.9.3. Tapped Density (Dt) using Vernier callipers.

It is the ratio of total mass of the powder to the tapped volume of 4.10.2. Weight variation:
the powder. Volume was measured by tapping the powder for
1000 times and the tapped volume was noted if the difference The compressed tablets were tested for weight uniformity. For
between these two volumes less than 2%. If it was more than 2%, this 20 tablets accurately weighed. After the obtained weight,
average weight was calculated. Each tablet’s weight was then
tapping continued for 1250 times and tapped volume was again
noted. It was expressed in g/ml and given by

compared with average weight to determine whether it was

Where M the mass of powder and Vt the tapped volume of the
within acceptable limits or not.
powder.
4.10.3. Hardness
3.9.4. Carr’s index (or) % compressibility
Hardness of tablets was measured using Pfizer type hardness
It indicated powder flow properties. It was expressed in tester. Three tablets were selected from each formulation
percentage and given by:- randomly and their hardness was measured. The means of
hardness values were calculated.4

4.10.4. Friability
where Dt; the tapped density of the powder and Db; the bulk
density of the powder. Friability of the tablets was determined by using Roche
friabilator. The weight of 20 tablets (initial weight) was subjected
to friabilator at 25 revolutions per 4 min. Tablets were then
4.9.5. Hausner ratio dedusted, reweighed (final weight) and percentage loss was
calculated. Friability is obtained by the following formula:
Hausner ratio is an indirect index of ease of powder flow. It was
calculated by the following formula.

4.10.5. Wetting time and water absorption ratio:

where, Dt; the tapped density and Db; the bulk density. Lower
hausner ratio (<1.25) indicated better flow properties than higher A double folded tissue paper was placed in a Petri dish. 6 mL of
ones (>1.25). water containing a water-soluble dye (eosin) was added to the
Petri dish. A tablet (pre-weighed) was carefully placed on the
4.9.5.1. Angle of repose surface of tissue paper.
The time required for water to reach the upper surface of the

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R. Kamboj et al. Journal of Medicinal and Chemical Sciences Original Article

tablet was noted as the wetting time. The wetted tablet was then 4.10.8. Stability Study:
weighed and the water absorption ratio (R) was determined by
using the equation: The optimized formulations were packed suitably and kept in
stability chamber at accelerated conditions (40 0C± 2
0
C/75%±5%RH) for a period of three months (Table 5). The
samples were analyzed at 30, 60 and 90 days for different
where Wa and Wb are the weights of tablet before (dry weight physiochemical parameters (Table 6) and in-vitro drug release
and after water absorption wet weight) respectively. (Fig. 2).

4.10.6. In vitro disintegration test: References:

In vitro disintegrating time was determined by using
1. V. Sharma, A. Philip, K. Pathak, AAPS Pharm. Sci. Tech. 2008, 9,
disintegration test apparatus without disk for six tablets. The 1530.
disintegration medium was 900 mL of distilled water kept at
(37.0°C) and stirred at a rate of (30) r/min. The time was 2. D. Shukla, S. Chakraborty, S. Singh, Sci. Pharm. 2009, 77, 327.
considered in seconds for complete disintegration of the tablet 3. S.S. Biradar, S.T. Bhagavati, I.J. Kuppasad, Internet J. Pharmacol.
with clear mass remains. (Table 3) 2006, 4, 32.
4. B.S. Kuchekar, A.C. Badhan, H.S. Mahajan, Indian Drugs. 2004, 41,
4.10.7. Dissolution studies: 592.
5. D. Sharma, D. Kumar, M. Singh, Int. Res. J. Pharmacy. 2012, 3,
In-Vitrodrug release studies were carried out by using USP 2230.
(TDT 06L) Type II (paddle type) dissolution test apparatus at 50 6. T.D. Nandgude, V.K. Chatap, K.S. Bhise, D.K. Sharma, Indian
rpm using pH 6.8 phosphate buffer as dissolution media Drugs, 2007, 44, 471.
maintained at the temperature of 37±0.5oC. Samples were 7. R.K. Rishi, Pharma. Rev. 2004, 34, 36.
withdrawn at specific time intervals and replaced with fresh
media and filtered. The amount of drug dissolved was 8. H. Rohm, K.G. Co, Drug Delivery Formulation. 2008, 4,109.
determined by spectrophotometrically at 250 nm (Table 4). The 9. N. Borodkin, D.P. J. Sandburg, Pharmaceutics Sci.1971, 60, 1523.
experiments were conducted in triplicate. The comparative 10. S. Pisal, AAPS Pharm. Sci. Tech. 2004, 5, 262.
results are shown as (Fig.1).
11. A.M. Aly, Pharmaceutics Technol. 2005, 68, 78.

How to cite this paper: R. kamboj, S. kamboj, A. Kumar,

Taste-masking assessment of orally disintegrating tablets of
valsartan using ion exchange resin. J. Med. Chem. Sci. 2018,
1, 11-17.
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