Solubilizer; drug delivery

Drugs are released from hypromellose in a regulated manner, which effectively lengthens the time the medication is released and its therapeutic effect [1]. Pharmaceuticals with prolonged release have long included hydroxypropyl methylcellulose, or hypromellose. These polymers are employed in matrix tablets, and when they come into touch with water, they hydrate and form a viscous gel barrier inside and around the tablet. The rate of water diffusion into the dry polymer, the rate of hydration and gel formation, the viscosity of hydrated hypromellose, and the rate of coagulation of hypromellose are among the hypromellose properties that influence drug release rates. Rate of glue erosion [2].

For dry eye syndrome, puncttal sealing with 2% hypromellose is an inexpensive and secure adjunctive treatment. Following hypromellose occlusion, there was a noticeable decrease in symptoms according to studies using fluorescein and rose bengal staining [3]. In mice given a high-fat diet, hypromellose can successfully enhance blood glucose metabolism and reduce oxidative stress. The modification of hepatic glucose-regulating enzyme activity and the activation of hepatic and erythrocyte antioxidant enzymes are partially responsible for the antihyperglycemic and antioxidant actions of hypromellose. Hypromellose can be employed as a biomaterial in the production of functional foods or as a medication to treat oxidative stress and hyperglycemia brought on by a high fat diet [4].

Intervention and Randomization [3]
Patients who met the inclusion criteria underwent a complete ophthalmic examination, answered a questionnaire, and rated their symptoms using a visual scale (score, 0–10: the higher the score, the greater the intensity of the symptom) considering the following symptoms: burning, itching, redness, FBS, and tearing. Schirmer test with anesthesia (basal tear secretion test),8 the tear film break-up time test, and fluorescein and rose bengal staining tests were performed. All tests were performed before the procedure, and at 28, and 56 days after occlusion.
After the tests, 1 eye was randomized to receive occlusion, whereas the other eye was not occluded (control). Both eyes were anesthetized with proxymetacaine 0.5%. All patients had a patent lacrimal drainage system detected by a patency test using saline. The lower lacrimal punctum of the selected eye was occluded using 0.05 mL of HPMC/hypromellose 2%, which was applied with a 26-gauge (0.4 mm) cannula inserted 2 mm into the vertical portion of the lower canaliculus. The procedure was observed using a slit lamp until there was a reflux of hypromellose through the lacrimal punctum, thus making it possible to assume that total appropriate occlusion was achieved. A simulation of the procedure was performed in the control eye. Screw syringes were used to prevent pressure exerted during the procedure from projecting the needle and injuring the eye. Patients were not aware of which eye was occluded. They were instructed to keep using all medications, including those administered by the ocular route.

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Animals and Diet [4]
Thirty-two male C57BL/6N mice of 4 weeks of age, weighing 12 g, were purchased from Orient Inc. (Seoul, Korea). They were individually housed in stainless steel cages in a room maintained at 25 °C with 50% relative humidity and 12/12 h light/dark cycle and fed with a pelletized chow diet for 2 weeks upon arrival. The animals were then randomly divided into 4 dietary groups (n = 8). The first and second mouse groups were fed with a normal control (NC) and a high fat (HF, 17%, w/w) diet, respectively. The other two groups were given a high fat diet supplemented with either HEMC (HF+HEMC) or HPMC (HF+HPMC). The composition of the experimental diet (Table 7) was based on the AIN-76 semisynthetic diet [29]. The mice were fed for 6 weeks and allowed free access to food and water during the experimental period. The food consumption and weight gain were measured daily and weekly, respectively. At the end of the experimental period, the mice were anaesthetized with ketamine-HCl following a 12-h fast. The blood samples were drawn from the inferior vena cava into a heparin-coated tube and centrifuged at 1,000 × g for 15 min at 4 °C to obtain the plasma and erythrocyte. The liver was removed, rinsed with physiological saline, and stored at −70 °C until analysis. The current study protocol was approved by the Ethics Committee of Kyungpook National University for animal studies.

[1]. The use of hypromellose in oral drug delivery. J Pharm Pharmacol. 2005 May;57(5):533-46.

[2]. Hypromellose films for the delivery of growth factors for wound healing. J Pharm Pharmacol. 2007 Mar;59(3):367-72.

[3]. Prospective evaluation of hypromellose 2% for punctal occlusion in patients with dry eye. Cornea. 2015 Feb;34(2):188-92.

[4]. Antihyperglycemic and antioxidative effects of Hydroxyethyl Methylcellulose (HEMC) and Hydroxypropyl Methylcellulose (HPMC) in mice fed with a high fat diet. Int J Mol Sci. 2012;13(3):3738-50.

Hypromellose, formerly known as hydroxypropylmethylcellulose (HPMC), is by far the most commonly employed cellulose ether used in the fabrication of hydrophilic matrices. Hypromellose provides the release of a drug in a controlled manner, effectively increasing the duration of release of a drug to prolong its therapeutic effect. This review provides a current insight into hypromellose and its applicability to hydrophilic matrices in order to highlight the basic parameters that affect its performance. Topics covered include the chemical, thermal and mechanical properties of hypromellose, hydration of the polymer matrices, the mechanism of drug release and the influence of tablet geometry on drug-release rate. The inclusion of drug-release modifiers within hypromellose matrices, the effects of dissolution media and the influence of both the external environment and microenvironment pH within the gel matrix on the properties of the polymer are also discussed. [1]

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Hypromellose was investigated as a carrier for extending topical growth factor delivery to wounds. Films of hypromellose (E4M, K4M and E10M) containing a model protein horseradish peroxidase (1% w/w HRP, MW 40 000) were cast from aqueous solutions and dried at 37 degrees C. In-vitro release was determined using Franz-type diffusion cells and films were mounted directly into the Franz cell or cast onto a wound dressing (Melolin) backing. There was an initial burst release then an extended release over 5 h. The Melolin backing significantly reduced the burst but not the extended release rates (P < 0.05). Release of HRP was also determined from 7% w/v hypromellose gels and was significantly lower for E10M than E4M, suggesting that, once hydrated, the E10M hypromellose provides the greatest resistance to HRP release. The release profile of basic fibroblast growth factor from Melolin-backed films made from E4M hypromellose was not significantly different at any time point to that of HRP release from the same formulation. Hypromellose may be incorporated into a wound dressing such as Melolin to provide a prolonged release of an incorporated protein active.[2]

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Purpose: The aim of this study was to evaluate the effectiveness of punctal occlusion using hypromellose 2% in patients with dry eye. Methods: In this prospective, randomized single-blinded clinical trial, we evaluated 76 eyes of 38 patients (36 women and 2 men) with dry eye secondary to rheumatic diseases. In each patient, the lower lacrimal punctum of 1 eye was occluded using hypromellose 2%, whereas the contralateral eye underwent a simulation of the procedure (control group). Patients' eyes were assessed for burning, itching, redness, foreign body sensation, and tearing based on a visual scale questionnaire (score, 0-10). We also performed objective tests for evaluation of dry eye using a Schirmer test with anesthesia (basal tear secretion test), the tear film break-up time test, and fluorescein and rose bengal staining tests at 0, 28, and 56 days after treatment. Results: Fluorescein and rose bengal staining tests showed that there was a significant reduction in signs after occlusion using hypromellose. The symptoms measured by the visual scale were significantly reduced. The values of the Schirmer test with anesthesia and the break-up time test increased significantly. The effects persisted for up to 8 weeks. There were no dropouts or reported side effects during the 24-month follow-up. Conclusions: Our results suggest that punctal occlusion using hypromellose 2% is a low-cost and safe additional treatment for dry eye. [3]

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The effect of dietary feeding of hydroxyethyl methylcellulose (HEMC) and hydroxypropyl methylcellulose (HPMC) on the glucose metabolism and antioxidative status in mice under high fat diet conditions was investigated. The mice were randomly divided and given experimental diets for six weeks: normal control (NC group), high fat (HF group), and high fat supplemented with either HEMC (HF+HEMC group) or HPMC (HF+HPMC group). At the end of the experimental period, the HF group exhibited markedly higher blood glucose and insulin levels as well as a higher erythrocyte lipid peroxidation rate relative to the control group. However, diet supplementation of HEMC and HPMC was found to counteract the high fat-induced hyperglycemia and oxidative stress via regulation of antioxidant and hepatic glucose-regulating enzyme activities. These findings illustrate that HEMC and HPMC were similarly effective in improving the glucose metabolism and antioxidant defense system in high fat-fed mice and they may be beneficial as functional biomaterials in the development of therapeutic agents against high fat dietinduced hyperglycemia and oxidative stress.[4]

C36H70O19.C20H38O11

1261.43872

9004-65-3

HPMC (Type II,Viscosity:5mPa.s);9004-65-3

White to off-white solid powder

1.39

Hypromellose (Type II,Viscosity:3mPa.s); (Hydroxypropyl)methyl cellulose (Type II,Viscosity:3mPa.s); Celacol HPM 5000 (Type II,Viscosity:3mPa.s); Hypromellose; 2-Hydroxypropyl Methyl Cellulose; 2-Hydroxypropyl Methyl Cellulose Ether; 40US; 60HD20000; 60MP4000; 60RT50; 60SH06; 60SH100; 60SH4000; 60SH4000F; 60SH5; 65SH-4000; 65SH5; 90SH100; 90SH100000; 90SH15000S; 90SH400; Accel R 100; BN 4; Benecel 324; Benecel 363; Benecel 424; Benecel K 35M; Benecel MP 3; Benecel MP 363C; Benecel MP 824; Benecel MP 843; Benecel MP 9; Benecel MP 943; Benecel MP 943W; Celacol 15000DS; Celacol HPM 15000DS; Celacol HPM 450; Celacol HPM 5000; Cellulose hydroxypropyl methyl ether; Cesca HPC 50; Courlose HPM; Culminal 1034; Fortefiber; Hydroxypropyl methyl cellulose; Hydroxypropyl methyl cellulose ether; Hypromelloc E 5; Hypromellose; Hypromellose 2208; Hypromellose 2910; Hypromellose E 15; Hypromellose E 5; Hypromellose K 100MCR; Magimix; Marpolose; Mecellose; Methocel; Methofas; Methyl hydroxypropyl cellulose; Metolose; Neovisco MC HM 4000; Neovisco MC RM 30000; Ni; 9004-65-3

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~25 mg/mL
H2O : ~10 mg/mL

Solubility in Formulation 1: 8.33 mg/mL (Infinity mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)