# Honey-Based Medicinal Formulations: A Critical Review
## 3 Honey-Based Medicinal Formulations
### Honey-Based Gels  
Honey can be formulated into gels/hydrogels by incorporating suitable gel-forming agent(s), with and without other supporting materials. FDA-approved commercial honey gels currently on the market (Table 1) typically contain the _Leptosperm_-derived Manuka honey. Honey is mixed with other agent(s) such as natural emollients, for example, myristyl myristate, plantacare, lanolin, propylene glycol, PEG-400, or different plant waves. While only limited clinical trial data or other levels of evidence for the claims made for these specific commercial formulations are publicly available, the effectiveness of such gels can be derived from various in vitro [1, 4, 14, 15, 16, 17] and in vivo studies [18, 19, 20], as well as from randomized clinical trials using noncommercial formulations, as summarized in Table 2[21, 22, 23]. The effectiveness of MedihoneyTM antibacterial wound gel has been demonstrated in published case reports [24, 25]. When localized wound infection is present, the wound is placed into a state of persistent inflammation, which can become uncomfortable for the patient. Associated problems such as increased exudate and malodor can be difficult to manage with topical dressings and can be distressing for the patient, adversely affecting their quality of life. The MedihoneyTM antibacterial gel is considered to be suitable for wound treatment and it assists with the management of all key symptoms generally found in wounds [24, 25]. A study led by [PERSON] et al. demonstrated that MedihoneyTM gel treatment significantly reduced wound size, pain, odor, and exudate, indicating that it reduced the bioburden of the wounds to enable them to progress toward healing [24]. A four-center feasibility study was undertaken by [PERSON] et al. to determine the effectiveness of MedihoneyTM for the treatment of leg ulcers in terms of pain relief, odor control, and overall patient satisfaction. The findings of this study demonstrated that MedihoneyTM gel decreased ulcer pain and size considerably and deodorized odorous wounds quickly [26]. Another widely used commercial product is Melcare's Manuka Wound GelTM comprising 80% Manuka honey and a natural emollient (in the form of plant-derived hydrocolloids and a natural oil) that is indicated as a contact layer for wounds such as venous ulcers, pressure ulcers (I-IV), diabetic ulcers, first- and second-degree burns, surgical wounds, donor and recipient graft sites, sloughy, malodorous wounds, and general first aid wound care. A honey-based gel can also be prepared with 100% honey without the addition of other ingredients. ActivonTM and ManukaPliTM gel, for instance, contain 100% medical grade Manuka honey sterilized by gamma radiation with no additives. On the other hand, Revamil GelTM, which is indicated for the management of a broad range of wounds, consists of 100% pure and sterilized Revamil Source (RS) honey. RS honey is produced by Bfactory Health Products (Rhenen, The Netherlands) under standardized conditions in greenhouses from healthy bee colonies living in a controlled environment. By utilizing this controlled production process, the company aims to provide reproducible wound healing  
* Manufacturer’s claim; given other ingredients are present, it is uncertain whether this refers to honey content or honey purity. \end{table}
Table 1: Cont. and antibacterial activity in their Revamil honey gel products. The factors responsible for the antibacterial activity of this honey are its high sugar concentration, the generation of H2O2, the 1,2-dicarbonyl compound methylglyoxal (MGO), and the cationic antimicrobial peptide bee defensin-1, as well as its low pH (3.2) which is at the lower end of the pH range (pH 3.2-4.5) found for honeys [27]. A low pH and high sugar content (common in all honeys) create an unfavorable environment for bacteria. A 2012 study by [PERSON] et al. found that RS honey diluted in water to between 40% and 20% produced high levels of H2O2, with a maximum concentration of 5.62 \(\pm\) 0.54 mM H2O2 formed in 30% honey [28].