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Aug 16,
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What is Methylcellulose (MC)?
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After the refined cotton is treated with alkali, cellulose ether is produced through a series of reactions with methane chloride as etherification agent. Generally, the degree of substitution is 1.6~2.0, and the solubility is also different with different degrees of substitution. It belongs to non-ionic cellulose ether.
(1) Methylcellulose is soluble in cold water, and it will be difficult to dissolve in hot water. Its aqueous solution is very stable in the range of pH=3~12. It has good compatibility with starch, guar gum, etc. and many surfactants. When the temperature reaches the gelation temperature, gelation occurs.
(2) The water retention of methyl cellulose depends on its addition amount, viscosity, particle fineness and dissolution rate. Generally, if the addition amount is large, the fineness is small, and the viscosity is large, the water retention rate is high. Among them, the amount of addition has a great influence on the water retention rate, and the level of viscosity is not directly proportional to the level of water retention rate. The dissolution rate mainly depends on the degree of surface modification of cellulose particles and particle fineness. Among the above cellulose ethers, methyl cellulose and hydroxypropyl methyl cellulose have higher water retention rates.
(3) Changes in temperature will seriously affect the water retention rate of methyl cellulose. Generally, the higher the temperature, the worse the water retention. If the mortar temperature exceeds 40°C, the water retention of methyl cellulose will be significantly reduced, seriously affecting the construction of the mortar.
(4) Methyl cellulose has a significant effect on the construction and adhesion of mortar. The &#;adhesion&#; here refers to the adhesive force felt between the worker&#;s applicator tool and the wall substrate, that is, the shear resistance of the mortar. The adhesiveness is high, the shear resistance of the mortar is large, and the strength required by the workers in the process of use is also large, and the construction performance of the mortar is poor. Methyl cellulose adhesion is at a moderate level in cellulose ether products.
What is Hydroxypropylmethylcellulose (HPMC)?
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Hydroxypropyl methylcellulose is a cellulose variety whose output and consumption have been increasing rapidly in recent years. It is a non-ionic cellulose mixed ether made from refined cotton after alkalization, using propylene oxide and methyl chloride as etherification agent, through a series of reactions. The degree of substitution is generally 1.2~2.0. Its properties are different due to the different ratios of methoxyl content and hydroxypropyl content.
(1) Hydroxypropyl methylcellulose is easily soluble in cold water, but it will encounter difficulties in dissolving in hot water. But its gelation temperature in hot water is significantly higher than that of methyl cellulose. The solubility in cold water is also greatly improved compared with methyl cellulose.
(2) The viscosity of hydroxypropyl methylcellulose is related to its molecular weight, and the larger the molecular weight, the higher the viscosity. Temperature also affects its viscosity, as temperature increases, viscosity decreases. However, its high viscosity has a lower temperature effect than methyl cellulose. Its solution is stable when stored at room temperature.
(3) The water retention of hydroxypropyl methylcellulose depends on its addition amount, viscosity, etc., and its water retention rate under the same addition amount is higher than that of methyl cellulose.
(4) Hydroxypropyl methylcellulose is stable to acid and alkali, and its aqueous solution is very stable in the range of pH=2~12. Caustic soda and lime water have little effect on its performance, but alkali can speed up its dissolution and increase its viscosity. Hydroxypropyl methylcellulose is stable to common salts, but when the concentration of salt solution is high, the viscosity of hydroxypropyl methylcellulose solution tends to increase.
(5) Hydroxypropyl methylcellulose can be mixed with water-soluble polymers to form a uniform and higher viscosity solution. Such as polyvinyl alcohol, starch ether, vegetable gum, etc.
(6) Hydroxypropyl methylcellulose has better enzyme resistance than methylcellulose, and its solution is less likely to be degraded by enzymes than methylcellulose. The adhesion of hydroxypropyl methylcellulose to mortar construction is higher than that of methylcellulose.
What is Hydroxyethyl Cellulose (CMC HEC)?
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It is made by treating refined cotton with alkali, then reacting with ethylene oxide as etherification agent in the presence of acetone. The degree of substitution is generally 1.5~2.0. It has strong hydrophilicity and is easy to absorb moisture.
(1) Hydroxyethyl cellulose is soluble in cold water, but it is difficult to dissolve in hot water. Its solution is stable at high temperature without gelling. It can be used for a long time under high temperature in mortar, but its water retention is lower than that of methyl cellulose.
(2) Hydroxyethyl cellulose is stable to general acid and alkali. Alkali can accelerate its dissolution and slightly increase its viscosity. Its dispersibility in water is slightly worse than that of methyl cellulose and hydroxypropyl methyl cellulose.
(3) Hydroxyethyl cellulose has good anti-sag performance for mortar, but it has a longer retarding time for cement.
(4) The performance of hydroxyethyl cellulose produced by some domestic enterprises is obviously lower than that of methyl cellulose due to its high water content and high ash content.
What is Carboxymethylcellulose (CMC)?
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Ionic cellulose ether is made from natural fibers (cotton, etc.) which are treated with alkali and used as etherification agent through a series of reaction treatments. The degree of substitution is generally 0.4~1.4, and its performance is greatly affected by the degree of substitution.
(1) Carboxymethyl cellulose is highly hygroscopic, and it will contain relatively large amounts of water when stored under normal conditions.
(2) Carboxymethyl cellulose aqueous solution will not produce gel, and the viscosity will decrease with the increase of temperature. When the temperature exceeds 50&#;, the viscosity is irreversible.
(3) Its stability is greatly affected by pH. Generally, it can be used in gypsum-based mortar, but not in cement-based mortar. When highly alkaline, it loses viscosity.
(4) Its water retention is far lower than that of methyl cellulose. It has a retarding effect on gypsum-based mortar and reduces its strength. However, the price of carboxymethyl cellulose is significantly lower than that of methyl cellulose
Difference Between HPMC And CMC
HPMC and CMC are two types of cellulose derivatives commonly used in various industries, including pharmaceuticals, food, cosmetics, and construction. While they share some similarities, there are distinct differences between HPMC (Hydroxypropyl Methylcellulose) and CMC (Carboxymethyl Cellulose) in terms of their chemical structure, properties, and applications. Let&#;s explore these differences in more detail:
Chemical Structure
HPMC: HPMC is a semisynthetic polymer derived from cellulose. It is created by chemically modifying cellulose through the addition of hydroxypropyl and methyl groups. This modification enhances the water retention and thickening properties of cellulose.
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CMC: CMC is also a semisynthetic polymer derived from cellulose. It is produced by chemically modifying cellulose through the addition of carboxymethyl groups. This modification imparts solubility in water and improves its binding, thickening, and stabilizing properties.
Water Solubility
HPMC: HPMC is not readily soluble in water but can swell and disperse in water to form a viscous solution or gel. The degree of solubility depends on the viscosity grade of HPMC and the temperature of the water.
CMC: CMC is highly soluble in water and forms a clear and viscous solution. It has excellent water retention and binding properties, making it suitable for applications that require thickening or stabilization.
Thermal Stability
HPMC: HPMC exhibits good thermal stability, meaning it can withstand high temperatures without significant degradation. This property makes it suitable for applications where heat resistance is required.
CMC: CMC also demonstrates good thermal stability and can tolerate moderate temperatures without notable degradation. However, it may exhibit some sensitivity to prolonged exposure to higher temperatures.
Viscosity
HPMC: HPMC is available in various viscosity grades, ranging from low to high viscosity. These different grades offer a range of thickness and water-holding capabilities, allowing for precise control over the rheological properties of formulations.
CMC: CMC is also available in different viscosity grades, providing a wide range of thickening capabilities. It can form stable and uniform suspensions, making it ideal for applications requiring viscosity control and stabilization.
Applications
HPMC: HPMC finds applications in various industries, including pharmaceuticals (tablet coatings, controlled release formulations), personal care products (lotions, creams, shampoos), construction (mortars, cement-based products), and food (emulsifiers, stabilizers).
CMC: CMC is widely used in industries such as food (thickeners, stabilizers, dietary fiber), pharmaceuticals (binding agents, viscosity modifiers), personal care products (toothpaste, creams, gels), and oil drilling (fluid viscosity control).
In summary, while both HPMC and CMC are cellulose derivatives, they differ in terms of their chemical structure, water solubility, thermal stability, viscosity characteristics, and applications. Understanding these differences is crucial for selecting the appropriate cellulose derivative for a specific application in industries ranging from pharmaceuticals and personal care to food and construction.
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The Difference Between Hydroxypropyl Methylcellulose Hpmc and Methylcellulose Mc
Kima Chemical Co., Ltd. is a reliable cellulose ether supplier to many global potential markets. With capacity of tons per year, Kima Chemical serves clients in domestic and global market in different industries, including construction, paint, pharmaceutical, food, personal care and oil drilling industries.
To compare the efficacy of carboxymethylcellulose 0.5% (CMC), hydroxypropyl-guar containing polyethylene glycol 400/propylene glycol (PEG/PG), and hydroxypropyl methylcellulose 0.3% (HPMC) as tear substitutes in patients with dry eye.
A retrospective evaluation of cases presenting with symptoms of dry eye from July to June was done. Patients with Ocular Surface Disease Index (OSDI) scoring >12 were included in the study. Parameters such as age, gender, Schirmer test (ST), and tear film breakup time (TBUT) were recorded on day 0, week 1, and week 4. For analysis, cases were divided into three groups; Group 1 &#; CMC, Group 2 &#; PEG/PG, and Group 3 &#; HPMC.
Overall, 120 patients were included in the study. Demographic data and baseline characteristics were comparable among the groups. Group 2 had significant improvement in percentage change in OSDI (weeks 0&#;1, 0&#;4, and 1&#;4, P = 0.00), TBUT (weeks 0&#;1, P = 0.01; 0&#;4, P = 0.006; and 1&#;4, P = 0.007), and in ST (weeks 0&#;1, P = 0.02; 0&#;4, P = 0.002; and 1&#;4, P = 0.008) compared to Group 1 at all follow-ups. Group 3 had improvements similar to Group 2, but it was not at all follow-ups (improvement in percentage change OSDI [weeks 0&#;1, 0&#;4, and 1&#;4, P = 0.00], TBUT [weeks 0&#;1, P = 0.10; 0&#;4, P = 0.03; and 1&#;4, P = 0.04], and in ST [weeks 0&#;1, P = 0.007; 0&#;4, P = 0.03; and 1&#;4, P = 0.12]). No significant difference was found between Groups 2 and 3.
Hydroxypropyl-guar containing PEG/PG and HPMC as tear substitutes are better than CMC. While HPMC was comparable to PEG/PG in subjective improvement, the objective improvement was not consistent.
Keywords:
Artificial tear, carboxymethylcellulose, dry eye, hydroxypropyl methylcellulose, Ocular Surface Disease Index, polyethylene glycol
Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability, with potential damage to the ocular surface.[1] It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.[1] Dry eye is one of the most common causes of ocular morbidity in patients presenting to an ophthalmology outpatient department. Approximately one out of seven individuals aged 65&#;84 years reports symptoms of dry eye often or all of the time.[2] Management of dry eye depends on the cause and severity of the condition.[1] Various strategies have been described for medical management of dry eye; these include, the topical use of lubricants (artificial tear substitutes), topical corticosteroids and anti-inflammatory therapies, cyclosporine ophthalmic emulsion, and the systemic use of antioxidants (e.g., omega-3 fatty acids).[1,2]
Artificial tears are aqueous solutions containing polymers that determine their viscosity, retention time, and adhesion to the ocular surface. Various polymers currently in use include cellulose derivatives (e.g., hydroxypropyl methylcellulose [HPMC], carboxymethylcellulose [CMC]), polyvinyl derivatives (e.g., polyvinyl alcohol), chondroitin sulfate, and sodium hyaluronate.[1,3] In mild-to-moderate cases, they are the mainstay of treatment. Artificial tears act by replenishing the deficient aqueous layer of the tear film and diluting the inflammatory cytokines.[1,2,3]
In this study, we compared the efficacy of three commonly used tear substitutes, i.e., CMC 0.5%, HPMC 0.3%, and hydroxypropyl-guar containing polyethylene glycol 400/propylene glycol (PEG/PG) in the treatment of patients with dry eye.
Medical records of all cases of clinically diagnosed dry eye attending the corneal clinic of Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India, from July to June , were reviewed. The protocol for this study was approved by the local Institutional Review Board/Ethical Committee. The study adhered to the tenets of the Declaration of Helsinki. Inclusion criteria for the study were cases with Ocular Surface Disease Index (OSDI) scoring[4] of >12 and cases in whom topical steroid in the form of loteprednol 0.5% and cyclosporine 0.05% was started along with topical lubricants. We excluded cases in whom only topical lubricants or either steroid or cyclosporine was prescribed, cases already on treatment for dry eye, cases in whom dry eye was secondary to some ocular or systemic disease, and patients with any concurrent disease or condition that could have complicated or interfered with the administration or evaluation of the study drug.
The OSDI is a validated questionnaire-based scoring system for diagnosis of dry eye.[5] It consists of 12 questions that provide a rapid assessment of the symptoms of ocular irritation and their impact on vision-related functions. The response to each item was scored from 0 (none of the time) to 4 (all of the time); an average score was generated and transformed into a scale of 0&#;100, with higher scores representing greater disability.[4,5,6]
For the purpose of analysis, the cases were categorized into three groups; Group-1 included cases prescribed CMC 0.5% four times a day (prepared at our compound pharmacy), Group-2 included cases prescribed with hydroxypropyl-guar containing PEG/PG (Systane Ultra, Novartis [India] Ltd.) twice a day, and Group-3 included cases prescribed with HPMC 0.3% (Genteal Eye Drops, Novartis [India] Ltd.). Details of demographic data such as age and sex were recorded. Parameters such as OSDI, tear film breakup time (TBUT), Schirmer test (ST), and slit-lamp examination findings were recorded at day 0 (before start of treatment), week 1, and week 4. Comparative analysis was done among different groups for improvement in OSDI scores, TBUT, and ST at each follow-up.
The efficacy variables included TBUT, ST, and OSDI score. All variables were evaluated at days 0, 1 week, and 4 weeks. A repeated measures analysis of variance (ANOVA) was used to test for mean treatment group differences by day changes from baseline of TBUT, ST, and individual OSDI scores. ANOVA test was used to compare mean differences between treatment groups at day 0, week 1, week 4 in the OSDI score, TBUT, ST, and age characteristics. To find out which of the three drugs were most effective, post hoc test (Games&#;Howell) is applied which compares the drugs one by one. The Chi-square test was used to compare treatment group differences in demographic characteristics.
One hundred and twenty patients were included in the study. Group 1 (CMC 0.5%), Group 2 (hydroxypropyl-guar containing PEG/PG), and Group 3 (HPMC 0.3%) included 41, 48, and 31 cases, respectively. Male patients accounted for 53.3% of the cases. The mean age in Group 1, Group 2, and Group 3 was 44.10 ± 17.82, 49.21 ± 15.31, and 42.58 ± 16.21 years, respectively. Demographic data were similar across treatment groups as shown in . The three groups were comparable in their baseline characteristics that included mean scores for OSDI (P = 0.462), mean TBUT (P = 0.172), and the mean scores for ST (P = 0.226) [ ]. Cases were divided into mild, moderate, and severe depending on the OSDI score (mild: 13&#;22 points, moderate: 23&#;32 points, and severe: 33&#;100 points).[7] There was no difference in severity between the three groups (P = 0.827) [ ].
Mean OSDI in Group 1 was 30.14 ± 11.57 at week 1 and 25.78 ± 11.86 at week 4. Mean OSDI in Group 2 was 24.88 ± 9.66 at week 1 and 14.28 ± 6.83 at week 4. Mean OSDI in Group 3 was 28.86 ± 15.83 at week 1 and 17.98 ± 11.89 at week 4. Patients in Group 2 had a significantly lower mean OSDI score than those in Group 1 at week 1 (P = 0.000) and at week 4 (P = 0.000). Patients in Group 3 had a significantly lower mean OSDI score than those in Group 1 at week 1 (P = 0.001) and at week 4 (P = 0.000). Patients in Group 2 and Group 3 had no significant difference in mean OSDI score at week 1 (P = 0.541) and week 4 (P = 0.717). Change in OSDI at 1 week in Group 1 was 16.32%, in Group 2, it was 35.13%, and in Group 3, it was 31.5%. Change in OSDI at week 4 in Group 1 was 29.17%, in Group 2, it was 62.9%, and in Group 3, it was 57.3%.
Patients in Group 2 had a significantly better percentage change in OSDI than those in Group 1; at 0&#;1 week (P = 0.000), 0&#;4 weeks (P = 0.000), and 1&#;4 weeks (P = 0.000) [ ]. Patients in Group 3 had a significantly better percentage change in OSDI than those in Group 1, at 0&#;1 week (P = 0.000), 0&#;4 weeks (P = 0.000), and 1&#;4 weeks (P = 0.000). Patients in Group 2 and Group 3 had no significant difference in percentage change in OSDI at 0&#;1 week (P = 0.138), 0&#;4 weeks (P = 0.45), and 1&#;4 weeks (P = 0.113).
Mean TBUT in Group 1 was 9.20 ± 2.15 at week 1 and 9.57 ± 1.88 at week 4. Mean TBUT in Group 2 was 8.88 ± 2.33 at week 1 and 9.96 ± 1.64 at week 4. Mean TBUT in Group 3 was 8.88 ± 2.43 at week 1 and 9.85 ± 1.64 at week 4. Patients in Group 2 had a significant increase in mean TBUT than those in Group 1 at week 1 (P = 0.003) and at week 4 (P = 0.001). Patients in Group 3 had no significant difference in improvement in TBUT than those in Group 1 at week 1 (P = 0.06), but there was significant improvement of TBUT at week 4 (P = 0.014). There was no significant difference in improvement of TBUT in Group 2 and Group 3 at week 1 (P = 0.984) and at week 4 (P = 0.936).
Percentage change in TBUT among the three groups is summarized in . Patients in Group 2 had a significantly better percentage change in TBUT than those in Group 1; at 0&#;1 week (P = 0.016), 0&#;4 weeks (P = 0.006), and 1&#;4 weeks (P = 0.007). Patients in Group 3 had no significant difference in percentage change in TBUT than those in Group 1 at 0&#;1 weeks (P = 0.105), but there was a significant difference at 0&#;4 weeks (P = 0.032) and 1&#;4 weeks (P = 0.046). Patients in Group 2 and Group 3 had no significant difference in percentage change in TBUT from 0 to 1 week (P = 0.996), 0 to 4 weeks (P = 0.984), and 1 to 4 weeks (P = 0.982).
Mean ST in Group 1 was 25.78 ± 8.03 at week 1 and 26.06 ± 7.57 at week 4. Mean ST in Group 2 was 24.25 ± 8.37 at week 1 and 26.33 ± 6.67 at week 4. Mean ST in Group 3 was 23.72 ± 9.93 at week 1 and 25.46 ± 8.52 at week 4. Patients in Group 2 exhibited significant improvement in ST than Group 1 at week 1 (P = 0.018) and week 4 (P = 0.000). Patients in Group 3 exhibited significant improvement in ST than those in Group 1 at week 1 (P = 0.028) and week 4 (P = 0.015). There was no significant difference in improvement of ST in Group 2 and Group 3 at week 1 (P = 0.994) and week 4 (P = 0.939).
The percentage change in ST in the three groups is summarized in . Patients in Group 2 had a significant difference in percentage change in ST than Group 1 at 0&#;1 week (P = 0.029), 0&#;4 weeks (P = 0.002), and 1&#;4 weeks (P = 0.008). Patients in Group 3 had a significant difference in percentage change in ST than those in Group 1 at 0&#;1 week (P = 0.033) and 0&#;4 weeks (P = 0.033), but no significant difference at 1&#;4 weeks (P = 0.120). Patients in Group 2 and Group 3 had no significant difference in percentage change in ST at 0&#;1 week (P = 0.997), 0&#;4 weeks (P = 0.863), and 1&#;4 weeks (P = 0.904).
Tear substitutes are an essential component of the treatment regimen of dry eye. The OSDI has been used previously for the diagnosis of dry eye.[5] The OSDI scoring is probably a more practical approach to evaluate the improvement in dry eye from a patient's perspective. In this study, both hydroxypropyl-guar containing PEG 400/PG and HPMC 0.3% were better compared to CMC 0.5% in improving the OSDI.
The improvement with hydroxypropyl-guar containing PEG/PG as a tear substitute was consistent at all follow-ups compared to CMC 0.5%. In addition to OSDI, improvement was also seen in other objective parameters analyzed, that is, ST and TBUT. Hydroxypropyl-guar containing PEG/PG works through a unique biphasic mechanism of action in which the product first binds to damaged hydrophobic areas of epithelial cells to add volume to the tear film, and then restructures the tear film by forming a protective gel matrix that provides long-lasting protection.[8] The high molecular weight (&#; kDa) hydroxypropyl-guar molecules, along with the natural mucin layer, prolong retention of the demulcents on the ocular surface, which provides sustained lubrication of the eye. This protects the ocular surface from further damage during the process of epithelial healing and remodeling.[8] In addition, the new formulation has sorbitol, which serves to optimize the viscosity of the drop through control of the aforementioned borate/hydroxypropyl-guar gel.[8,9] In clinical studies, the daily use of PEG/PG, for 28 days or more in patients with dry eye, has been consistently associated with significant decrease in conjunctival and/or corneal staining,[10,11,12,13,14] increase in TBUT (invasive or noninvasive),[13,15] in patient-assessed parameters (drop comfort, ocular comfort, and dry eye symptoms), and a significantly greater ocular protection index.[15] The result of our study corroborates with those of previous studies. Thus, it can be concluded that hydroxypropyl-guar containing PEG/PG can lead to early and sustained relief in both objective and subjective parameters compared to CMC 0.5% tear substitutes.
The percentage change in OSDI in Group 3 cases on HPMC, when compared to those in Group 1, showed a trend similar to patients in Group 2, with significantly better change at all follow-up. This can be attributed to hydroxypropyl methylcellulose's superior cohesive and emollient properties compared to CMC.[16] However, unlike Group 2, the improvement in objective parameters such as TBUT was not consistent throughout the entire follow-up period. It was significant at week 1&#;4 and 0&#;4 but not in the 1st week (0&#;1 week) of starting therapy. The percentage change in ST was also inconsistent unlike Group 2. It was significant at 0&#;1 week (P = 0.007) and 0&#;4 weeks (P = 0.033) but not significant at 1&#;4 weeks' follow-up (P = 0.120). When Groups 2 and 3 were compared, no significant difference was found in any of the parameters at any follow-up. Thus, it can be said, although HPMC can provide immediate symptomatic relief to patients with dry eye similar to hydroxypropyl-guar containing PEG/PG, in terms of objective improvement such as TBUT and ST, it is not as consistent as hydroxypropyl-guar containing PEG/PG.
The limitation of using OSDI scoring is that it can be biased by possible mistakes owing to misunderstanding of words, reflecting individual and regional differences in word choice, rather than different quality of responses.[5,6] Moreover, the level of tolerance can also vary among different patients. All these factors can lead to variable scores even in patients with equal severity of dryness. Also, a study by Fenga et al.[6] found that OSDI is not as reliable as tear osmolarity for diagnosis of dry eye. To avoid such bias, we included both TBUT and ST, which showed results similar to OSDI scoring.
To conclude, both artificial tears such as hydroxypropyl-guar containing PEG 400/PG and HPMC 0.3% are equally effective in improving the subjective component of dry eye while the improvement in objective parameters is more consistent with hydroxypropyl-guar containing PEG 400/PG tear substitutes.
Nil.
There are no conflicts of interest.
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