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 methylcellulose (HPMC), formerly known as hydroxypropyl methylcellulose, is the most commonly used cellulose ether for preparing hydrophilic matrices. Hydroxypropyl methylcellulose can release drugs in a controlled manner, effectively prolonging the drug release time and thus prolonging its therapeutic effect. This article reviews hydroxypropyl methylcellulose and its application in hydrophilic matrices, focusing on the basic parameters that affect its performance. The content covers the chemical, thermal and mechanical properties of hydroxypropyl methylcellulose, the hydration of the polymer matrix, the drug release mechanism and the effect of tablet geometry on the drug release rate. In addition, this article also discusses the effects of adding drug release modifiers and dissolution media to the hydroxypropyl methylcellulose matrix, as well as the effects of the external environment and the pH value of the microenvironment inside the gel matrix on the polymer properties. [1] Hydroxypropyl methylcellulose has been studied as a carrier to prolong the delivery time of local growth factors to wounds. Hydroxypropyl methylcellulose (E4M, K4M, and E10M) films containing the model protein horseradish peroxidase (1% w/w HRP, molecular weight 40,000) were cast from aqueous solution and dried at 37°C. In vitro release was measured using a Franz diffusion cell, with the films either directly mounted into the cell or cast onto a Melolin backing. Results showed an initial burst release followed by sustained release over 5 hours. The Melolin backing significantly reduced the burst release rate but had no significant effect on the sustained release rate (P < 0.05). Furthermore, HRP release from 7% w/v hydroxypropyl methylcellulose gel was measured, with results indicating that E10M released significantly less HRP than E4M, suggesting that E10M hydroxypropyl methylcellulose exhibited the strongest resistance to HRP release after hydration. The release curve of basic fibroblast growth factor in Melolin backing film made of E4M hydroxypropyl methylcellulose was not significantly different from that of horseradish peroxidase (HRP) in the same formulation at any time point. Hydroxypropyl methylcellulose can be added to wound dressings such as Melolin to achieve sustained release of the active proteins contained therein. [2]

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Objective: This study aimed to evaluate the efficacy of punctal occlusion with 2% hydroxypropyl methylcellulose for the treatment of dry eye. Methods: In this prospective, randomized, single-blind clinical trial, we evaluated 76 eyes of 38 patients (36 women and 2 men) with dry eye secondary to rheumatic disease. The lower punctum of one eye of each patient was occluded with 2% hydroxypropyl methylcellulose, while the contralateral eye was occluded (control group). We assessed patients’ eye burning, itching, redness, foreign body sensation and tearing using a visual rating scale questionnaire (scoring range 0-10). In addition, we performed objective examinations at 0, 28 and 56 days after treatment to assess dry eye, including the basal tear secretion test under anesthesia (basal tear secretion test), tear film breakup time test and fluorescein and rose staining test. Results: The fluorescein and rose staining test showed that symptoms were significantly reduced after hydroxypropyl methylcellulose occlusion. Symptoms assessed by the visual rating scale were also significantly reduced. The values of the basal tear secretion test and tear film breakup time test under anesthesia were significantly increased. These effects lasted for up to 8 weeks. During the 24-month follow-up period, no subjects withdrew from the study or reported any side effects. Conclusion: Our results suggest that punctal occlusion with 2% hydroxypropyl methylcellulose is a low-cost and safe adjunctive treatment for dry eye. [3] This study investigated the effects of feeding hydroxyethyl methylcellulose (HEMC) and hydroxypropyl methylcellulose (HPMC) on glucose metabolism and antioxidant status in mice under a high-fat diet. Mice were randomly divided into three groups and fed experimental diets for six weeks: normal control group (NC group), high-fat group (HF group), and high-fat diet groups supplemented with HEMC (HF+HEMC group) or HPMC (HF+HPMC group), respectively. At the end of the experiment, compared with the control group, the HF group had significantly higher blood glucose and insulin levels and higher erythrocyte lipid peroxidation rate. However, the study found that dietary supplementation with HEMC and HPMC could counteract the hyperglycemia and oxidative stress caused by high-fat diet by regulating the activity of antioxidant enzymes and hepatic glucose-regulating enzymes. These findings suggest that HEMC and HPMC have similar effects in improving glucose metabolism and antioxidant defense systems in mice on a high-fat diet, and they may have potential application value as functional biomaterials in the development of drugs to treat hyperglycemia and oxidative stress caused by high-fat diet. [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.)