Macrogol 6000 is a PEG, a biologically inert mixture of long, linear, non-absorbable, non-metabolizable ethylene glycol polymers. 

The name defines the structure of the molecule:

• Macrogol is a name for polyethylene glycol (PEG), which is a polymer of ethylene oxide. The basic repetitive unit of PEG is -O-CH2-, derived from ethylene oxide (C2H4O).
• 6000 refers to the average molecular weight of the polymer that contains a sufficient number of repeating units of ethylene oxide to achieve an average molecular weight of 6000 g/mol. Since the molecular weight of the repeating unit (ethylene oxide) is about 44 g/mol, this means that there are on average about 136 repeating units in each molecule of Macrogol 6000.

Description of the raw materials used in its production:

• Ethylene Glycol is a key raw material for the synthesis of Macrogol 6000. It is a diol used in the production of polyethylene glycols.

The synthesis process takes place in different steps:

• The process begins with ethylene oxide,  a cyclic ether. This compound is highly reactive due to tension in the three-member ring.
• Ethylene oxide is reacted with a small amount of water in a process known as ring-opening polymerization. This reaction is catalyzed by a strong base or acid.
• The water molecule attacks the ethylene oxide, causing the ring to open and ethylene glycol to form.
• This process is repeated many times, with each new ethylene oxide molecule being added by reacting with the hydroxyl group at the end of the growing polymer chain.
• The reaction goes on until the polymer has reached the desired average molecular weight, in this case 6000.

It occurs as a fine white powder, white flakes or clear colorless liquid.

What it is used for

• Suppository Base - Macrogol 6000 can be used in the production of suppositories as an excipient.
• Coating Agent - Used to coat tablets to enhance their release properties or appearance.
• Solvent and Vehicle - In pharmaceutical preparations, it can act as a solvent or vehicle for active ingredients.
• Osmotic Laxative - When taken orally, it can act as a laxative by drawing water into the intestines and facilitating bowel movement.
• Plasticizing Agent - Used in pharmaceutical formulations to make tablets more pliable or malleable.

It is normally used for the treatment of constipation in children although recent studies have preferred lactulose (1) or electrical stimulation of the colon especially in the presence of Parkinson's disease (2).

Macrogol 6000 is an excipient commonly used for the preparation of solid-dispersion tablets because of its solubilizing, surface absorption properties. Macrogols in general are widely used as carriers because of some peculiar positive characteristics: low melting point, rapid solidification the ability to form solid drug solutions (3). 

Macrogol 6000 studies

 Caratteristiche tipiche ottimali del prodotto commerciale Macrogol 6000 

• Formula molecolare:  C₁₅H₂₁ClN₂OS      (C₂H₄O)nH₂O  
• Molecular Formula:  C₁₅H₂₁ClN₂OS     H(OCH₂)NOH    H(OCH2CH2)nOH
• Molecular Weight: 312.9 g/mol
• CAS: 25322-68-3      15272-95-4
• UNII 
• EC Number: 500-038-2
• DSSTox Substance ID: 
• MDL number  MFCDO1779614
• PubChem Substance ID 
• InChl  1S/C15H20N2OS.ClH/c1-3-17(4-2)10-9-16-15(18)14-11-12-7-5-6-8-13(12)19-14;/h5-8,11H,3-4,9-10H2,1-2H3,(H,16,18);1H
• InChI Key      TZBAVQKIEKDGFH-UHFFFAOYSA-N
• SMILES    CC[NH+](CC)CCNC(=O)C1=CC2=CC=CC=C2S1.[Cl-]
• IUPAC 
• ChEBI    

Synonyms: 

• Benzo(b)thiophene-2-carboxamide, N-(2-(diethylamino)ethyl)-, monohydrochloride

Where to buy Macrogol 6000

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A premise on PEG

Since the PEG family is numerous and is found in many cosmetic, cleaning and medicinal products and others, we need a cognitive premise on the subject that is rather complex from the point of view of safety because these products not only come into contact with the skin but, as in the case of medicine, they are also ingested.

PEG or polyethylene glycols polymerise the condensed ethylene oxide and water and are called polyethylene glycols, but in reality, they are complex chemical components, polymers bound together. For example,  plastic is polyethylene and has a hard consistency, while  polyethylene aggregated to the glycol forms a liquid.

The number that appears after the initials PEG represents the molecular weight and the higher this number is, the less it penetrates  the skin.

Here below are some studies in Medicine that refer to the use of PEG Polyethylene glycol in various fields.

Intestine

Polyethylene glycol with or without electrolytes is effective for the treatment of functional constipation, both in adults and in paediatric patients, with great safety and tolerability. These preparations are the most effective osmotic laxatives (more than lactulose) and are the first-line treatment for functional constipation in the short- and long-term. They are as effective as enemas in faecalomas, avoid the need for hospitalisation and are well tolerated by patients (especially when given without electrolytes) (4).

In the preparation  for colonoscopy,  polyethylene glycol tablets confirmed efficacy, acceptability, tolerance and safety similar to those of sodium phosphate (5).

For peripheral nerve repair (6).

Eyes

Dry eye syndrome is a disorder that affects 5-34% of the world's adult population with reduced quality of life. Artificial or lubricating tears are the most used therapy for treating this condition due to their low side effects profile, which attempt to modify the properties of the tear film. Polyethylene glycol has demonstrated clinical efficacy in the treatment of this condition (7).

Brain

Polyethylene glycol facilitates the neuroprotective effects of magnesium in head injuries (8).

Tumours

For transarterial chemoembolization, Polyethylene glycol is effective and safe for the treatment of liver cancer, as indicated by good tolerability, quality of life and high tumour response (9).

Cosmetics

Many types of PEG are hydrophilic and are used as creams, topical dermatological preparations and in cosmetic products such as surfactants, emulsifiers, detergents, humectants and skin conditioners.

Safety varies from type to type given the structural complexity (10).

Bibliografia_______________________

(1) Shatnawi MS, Alrwalah MM, Ghanma AM, Alqura'an ML, Zreiqat EN, Alzu'bi MM. Lactulose versus polyethylene glycol for disimpaction therapy in constipated children, a randomized controlled study. Sudan J Paediatr. 2019;19(1):31–36. doi:10.24911/SJP.106-1546805996

(2) Bu J, Qiao X, He Y, Liu J. Colonic electrical stimulation improves colonic transit in rotenone-induced Parkinson's disease model through affecting enteric neurons. Life Sci. 2019;231:116581. doi:10.1016/j.lfs.2019.116581

(3) Bley H, Fussnegger B, Bodmeier R. Characterization and stability of solid dispersions based on PEG/polymer blends. Int J Pharm. 2010 May 10;390(2):165-73. doi: 10.1016/j.ijpharm.2010.01.039. 

(4) Mínguez M, López Higueras A, Júdez J. Use of polyethylene glycol in functional constipation and fecal impaction.  Rev Esp Enferm Dig. 2016 Nov

Santos-Jasso KA, Arredondo-García JL, Maza-Vallejos J, Lezama-Del Valle P.  Effectiveness of senna vs polyethylene glycol as laxative therapy in children with constipation related to anorectal malformation.  J Pediatr Surg. 2016 Oct

(5) Chaussade S, Schmöcker C, Toulemonde P, Muñoz-Navas M, O'Mahony V, Henri F. Phosphate tablets or polyethylene glycol for preparation to colonoscopy? A multicentre non-inferiority randomized controlled trial. Surg Endosc. 2016 Nov

Tsunoda T, Sogo T, Iwasawa K, Umetsu S, Oikawa-Kawamoto M, Inui A, Fujisawa T. Feasibility and safety of bowel cleansing using low-volume polyethylene glycol with ascorbic acid before pediatric colonoscopy: A pilot study.  Dig Endosc. 2016 Oct 

(6) Hoffman AN, Bamba R, Pollins AC, Thayer WP. Analysis of polyethylene glycol (PEG) fusion in cultured neuroblastoma cells via flow cytometry: Techniques & optimization. J Clin Neurosci. 2016 

(7) Pérez-Balbuena AL, Ochoa-Tabares JC, Belalcazar-Rey S, Urzúa-Salinas C, Saucedo-Rodríguez LR, Velasco-Ramos R, Suárez-Sánchez RG, Rodríguez-Carrizalez AD, Oregón-Miranda AA. Efficacy of a fixed combination of 0.09 % xanthan gum/0.1 % chondroitin sulfate preservative free vs polyethylene glycol/propylene glycol in subjects with dry eye disease: a multicenter randomized controlled trial.  BMC Ophthalmol. 2016 Sep

Labetoulle M, Messmer EM, Pisella PJ, Ogundele A, Baudouin C. Safety and efficacy of a hydroxypropyl guar/polyethylene glycol/propylene glycol-based lubricant eye-drop in patients with dry eye.  Br J Ophthalmol. 2016

(8) Busingye DS, Turner RJ, Vink R.  Combined Magnesium/Polyethylene Glycol Facilitates the Neuroprotective Effects of Magnesium in Traumatic Brain Injury at a Reduced Magnesium Dose.  CNS Neurosci Ther. 2016

(9) Aliberti C, Carandina R, Sarti D, Mulazzani L, Catalano V, Felicioli A, Coschiera P, Fiorentini G.  Hepatic Arterial Infusion of Polyethylene Glycol Drug-eluting Beads for Primary and Metastatic Liver Cancer Therapy.  Anticancer Res. 2016

(10) Jang HJ, Shin CY, Kim KB. Safety Evaluation of Polyethylene Glycol (PEG) Compounds for Cosmetic Use.  Toxicol Res. 2015 Jun

Compendium of the most significant studies with reference to properties, intake, effects.

Fu CC, Wu CY, Chien CC, Hsu TH, Ou SF, Chen ST, Wu CH, Hsieh CT, Juang RS, Hsueh YH. Polyethylene Glycol6000/carbon Nanodots as Fluorescent Bioimaging Agents. Nanomaterials (Basel). 2020 Apr 3;10(4):677. doi: 10.3390/nano10040677.

Abstract.  We used 1,3, 6-trinitropyrene (TNP) and polyethylene glycol6000 (PEG6000) in a hydrothermal method to prepare functional polyethylene glycol6000/carbon nanodots (PEG6000/CDs) and analyzed their potential in fluorescent staining of different types of bacteria. Our results demonstrated that PEG6000/CDs stained the cell pole and septa of gram-positive bacteria B. Subtilis and B. thuringiensis but not those of gram-negative bacteria. 

Kraciuk R, Sznitowska M. Effect of different excipients on the physical characteristics of granules and tablets with carbamazepine prepared with polyethylene glycol 6000 by fluidized hot-melt granulation (FHMG). AAPS PharmSciTech. 2011 Dec;12(4):1241-7. doi: 10.1208/s12249-011-9698-7.

Abstract.  The objective of this study was to investigate the properties of granules and tablets with carbamazepine which were prepared employing a fluidized hot-melt granulation (FHMG) technique. The FHMG process was carried out at 65°C. Macrogol 6000 (PEG 6000) was used as a binder at the content 10% (w/w) of the granulated mass.

Serrati S, Martinelli C, Palazzo A, Iacobazzi RM, Perrone M, Ong QK, Luo Z, Bekdemir A, Pinto G, Cavalleri O, Cutrignelli A, Laquintana V, Denora N, Stellacci F, Krol S. Reproducibility warning: The curious case of polyethylene glycol 6000 and spheroid cell culture. PLoS One. 2020 Mar 19;15(3):e0224002. doi: 10.1371/journal.pone.0224002.

Abstract. In this study, we used PEG6000 samples from different distributors and tested their capability inducing spheroid formation upon surface coating. MALDI-MS, NMR, FTIR, and Triple SEC analysis of the different PEG60000s showed nearly identical physicochemical properties different, with only minor differences in mass and hydrodynamic radius, and AFM analysis showed no significant differences in the surface coatings obtained with the available PEG6000s.

Antosik-Rogóż A, Szafraniec-Szczęsny J, Chmiel K, Knapik-Kowalczuk J, Kurek M, Gawlak K, Danesi VP, Paluch M, Jachowicz R. How Does the CO2 in Supercritical State Affect the Properties of Drug-Polymer Systems, Dissolution Performance and Characteristics of Tablets Containing Bicalutamide? Materials (Basel). 2020 Jun 25;13(12):2848. doi: 10.3390/ma13122848.

Abstract. In this paper, we describe the application of scCO2 in the preparation of binary systems containing poorly soluble antiandrogenic drug bicalutamide and polymeric excipients, either Macrogol 6000 or Poloxamer®407. The changes in the particle size and morphology were followed using scanning electron microscopy and laser diffraction measurements.

Ge Y. An investigation into the mechanisms of rapid release of standard extract from Ginkgo biloba leaf in polyethylene glycol 6000 solid dispersions. Yakugaku Zasshi. 2010 Mar;130(3):425-30. doi: 10.1248/yakushi.130.425.

 Abstract. The rapid-release mechanisms of standard extract from Ginkgo biloba leaf (EGb) in the polyethylene glycol (PEG) 6000 dispersions were investigated.