Study of some O/W Gels Containing Natural Ingredients with Wound Healing Properties

OZON Emma Adriana1#, IONIȚĂ Elena Iuliana2#, LUPULEASA Dumitru1#, DUMITRESCU Denisa Elena3#, HÎNCU Lucian1#, MITITELU Magdalena4#

1Pharmaceutical Technology Department, Faculty of Pharmacy, ”Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, 020956, Bucharest (ROMANIA)

2Pharmacognosy, Phytochemistry, Phytotherapy Department, Faculty of Pharmacy, ”Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, 020956, Bucharest (ROMANIA)

3Organic Chemistry Department, Faculty of Pharmacy, Ovidius University, Mamaia Blvd. 124, 900527, Constanta (ROMANIA)

4 Clinical Laboratory and Food Hygiene Department, Faculty of Pharmacy, ”Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, 020956, Bucharest (ROMANIA)

 Authors emails: emmacretu@yahoo.com, ionita_elena_iuliana@yahoo.com, lupuliasa.dumitru@umfcd.rodenisadumitrescu@yahoo.com, lucianhincu@gmail.com, magdamititelu@yahoo.com

#Author Contributions: All authors have equally contributed to the work reported

Abstract 

     The objective of this study was to develop and evaluate carbopol gels with alcoholic plant extracts and vegetable oils. Four O/W gels were prepared and characterized in the present study, using as active ingredients Calendula tincture in different amounts (1%, 3%, 5%, 7%), 1% of each Sea buckthorn and Chamomile oils, one O/W emulsifier (Tween 80) and Carbopol 940 gel 2% as gel base. Were analysed the rheological characteristics (viscosity and spreadability) in order to select the optimal formulas.

Keywords: gels, viscosity, spreadability, tincture of calendula, vegetable oils

Introduction

     Hydrogels are three-dimensional networks made up of hydrophilic polymer chains that can retains large amounts of water or physiological fluids. In terms of biological interactions at molecular level, water content and elasticity, they are similar to natural biological tissues. Many polymers have been used to obtain hydrogels for biomedical use water-soluble, both natural and synthetic, both homopolymers and copolymers. Although hydrogels from natural polymers may not be sufficiently mechanically resistant, may contain pathogens, or generate immune or inflammatory responses, they have a number of advantageous properties, such as biocompatibility, biodegradability and are biologically recognizable entities that support cellular activity [1,2,3,4].

     In the experimental part were formulated four O/W gels with natural alcoholic and oily extracts. The natural extracts embedded in the gel base have known healing properties. Marigold tincture is a hydroalcoholic solution obtained by cold preparation from the flowers of the Calendula officinalis plant. Marigold tincture is used in preparations for external use for its healing, anti-inflammatory, antiseptic and antibacterial action. Sea buckthorn oil is most often obtained by the mechanical process of cold pressing either from the pulp of fruits (Fructus Hippophae) or from sea buckthorn seeds (Semen Hippophae). Sea buckthorn oil is rich in antioxidants and has remarkable healing properties. Chamomile flower oil is considered one of the oils with the most complex medicinal effects, which is why it is often used in folk medicine. Among the health benefits of chamomile essential oil, herbalists mention its antispasmodic, anti-inflammatory, healing, analgesic, bactericidal, sweating and deworming properties [5,6,7]. The natural ingredients used in pharmaceutical forms must be carefully selected so that they come from unpolluted environments, because pollutants can also contaminate natural extracts [8-13].

     Carbopole was used as the gel base due to the physical properties of the Carbopol gels. The time they stay on the application area, and the drug release rates are extremely sensitive to the rheological behaviour of the topical gel formulations [3,14,15]. For the emulsification of the extracts in the gel base, we selected Tween 80 as an O / W type emulsifier at a concentration of 0.5% due to the fact that it is a non-ionic surfactant, with a high emulsifying capacity and low toxicity [15].

Materials and Methods

     The gels were prepared according to the formulations presented in table 1, using an electronic mixer at 300 rpm speed and room temperature. The obtained gels were subjected to the quality control test, analysing the organoleptic properties (appearance, colour, smell), the pH in aqueous phase with pH-meter, the spreadability and the viscosity [15].

      The gels rheograms were determined using a rotational viscometer Rheotest 2.5, produced by RHEOTEST Messgeräte Medingen GmbH, Germany. In order to analyse the flowing characteristics of the gels, the following rheological parameters were registered: dynamic viscosity (η in cP), shear speed (Dr  in s-1) and shear tension (τr in dyne/cm2).

     The spreadability of the gels was examined at 48 h after preparation by Ojeda Arbussa method. 

Table 1. Gels formulation

COMPONENTS FORMULATION A  FORMULATION B FORMULATION C FORMULATION D
Calendula tincture 1g 3g 5g 7g
Sea buckthorn oil 1g 1g 1g 1g
Chamomile oil 1g 1g 1g 1g
Tween 80 0.3g 0.3g 0.3g 0.3g
Carbopol 940 gel  2% to 100g to 100g to 100g to 100g

Results and Discussions

     The prepared gels presented a homogeneous appearance, a pleasant characteristic smell, with different colours from light yellow to dark brown, depending on the Calendula tincture concentration (fig.1). These characteristics were maintained during the 30 days of storage at room temperature conditions.

Figure 1. Appearance of the gels in comparison with carbopol gel alone

Table 2. pH values for the four studied gels

FORMULATION TYPE pH value, immediately after preparation pH value, 30 days after preparation
A 6.2 6.1
B 6.4 6.4
C 6.8 6.8
D 6.8 6.6

All obtained gels had pH values suitable to be applied on the skin, without causing any irritation (table 2).

   The gel rheograms, τ = f (η, Dr) and their spreadability are presented in the following figures (fig. 2-5):         

     τ                              

Figure 2. 

Shear tension variation with shear speed (2.a) and 

viscosity variation with shear tension (2.b) for formula A

î

 According to the results registered in figures 2 and 3 we can notice a more evident rising of shear tension with shear speed at formulation B compared to formulation A. Formulation A presents a more extended field for viscosity variation reported to shear tension, than product B (0 – 6500 cP).

 Formulation C (fig. 4) presents a more abrupt increase of shear tension with rotating moment but a much slow decreasing viscosity with a higher turning point than formulations A and B. Formulation D (fig. 5) presents a more abrupt decreasing of viscosity with the rise of shear tension than formula C, but the variation field of viscosity is similar. Considering the ingredients included in the four formulations, we can conclude that the viscosity is influenced by the concentration of Calendula tincture, increasing with the amount of tincture added. Still, all four proposed and studied formulations present a pseudoplastic character, being suitable for use on the skin.

                     S (mm2)

Figure 6. The spreadability of Carbopol 940 gel 2%

Figure 8. The spreadability for formulation B

Figure 10. The spreadability for formulation D

    From figures 6 to 10, we can observe that the spreading area increases with the weights added for all four formulations, the values showing an insignificant variation between them and in comparsion with carbopol gel alone. The studied gels are showing a good spreadability that remains almost unchanged during the first 30 days after preparation. According to the obtained data, the highest consistency is appeared to be for B and C formulations.

Conclusions    

   Four O/W gels were prepared and characterized in the present study, using as active ingredients Calendula tincture in different amounts (1%, 3%, 5%, 7%), 1% of each Seabuckthorn and Chamomile oils, one O/W emulsifier (Tween 80) and Carbopol 940 gel 2% as gel base. After preparation, the studied products had an adequate pH, which was maintained for 30 days of observation. They all showed a good spreadability, similar with the gel base alone, and also a good flowability, being suitable to be applied on the skin.

REFERENCES

  1. Hoffman, A. S. (2002). Hydrogels for biomedical applications, Adv. Drug Deliv. Rev. 43, 3 
  2. Gan, L.L., Nong, L.P. (2010). Study on swelling performance of chitosan/gelatin/PVA complex hydrogel. Chemistry and Bioengineering, 27 (9), 33
  3. Kim, J. Y., Song, J. Y., Lee, E. J., Park, S. K. (2003). Rheological properties and microstructures of Carbopol gel network system.Colloid Polym. Sci, 281:614–623.
  4. Parenteau-Bareil, R., Gauvin, R., Berthod, F. (2010). Collagen-Based Biomaterials for Tissue Engineering Applications,Materials, 3,1863
  5. Muntean, L.S., Tămaş, M., Muntean, S., Muntean, L., Duda, M., Vârban, D., Florian S. (2017). Tratat de plante medicinale cultivate şi spontane, Ed. Risoprint, Cluj-Napoca, Ediţia a II-a.
  6. Ioniță, A. C., Mititelu, M., Nicolescu, T. O., Nicolescu, F., Moroșan, E., Ozon, E. A., Ioniță, E. I. (2020). Research on the Hypolipidemic Action of Almond Oil and Almond Seeds. Proceedings of 6 th International Conference on Interdisciplinary Management of Diabetes Mellitus and its Complications INTERDIAB (Bucharest, Romania, 5-7 March 2020), Filodiritto Editore – Proceedings, pp. 326-331
  7. Ghica, M., Băncescu, I., Udeanu, D. I., Tăerel, A., Arsene, A. L., Anuța, V., Velescu, B. Șt., Gerghiceanu, F., Mititelu, M., Ioniță, A. C. (2020). Computational Approach for Small Data in Animal Models with Induced Metabolic Disorders, Proceedings of 6 th International Conference on Interdisciplinary Management of Diabetes Mellitus and its Complications INTERDIAB (Bucharest, Romania, 5-7 March 2020), Filodiritto Editore – Proceedings, pp. 98-106
  8. Mititelu, M., Nicolescu, T. O., Ioniță, A. C., Nicolescu, F. (2012), Heavy Metals Analisys in Some Wild Edible Mushrooms, Journal of Enviromental Protection and Ecology 13(2A), pp. 875-879 
  9. Mititelu, M., Nicolescu, T. O., Ioniță, A. C., Nicolescu, F. (2012). Study of Heavy Metals and Organic Polluants From Some Fisches of Danube River. Journal of Enviromental Protection and Ecology 13(2A), pp. 869-874 
  10. Mititelu, M., Ghica, M., Ioniţă, A. C., Moroşan, E.  (2019), The influence of heavy metals contamination in soil on the composition of some wild edible mushrooms, Farmacia 67(3), pp. 398-404
  11. Mititelu, M., Moroşan, E., Neacșu, S. M., Ioniţă, E. I. (2018). Research regarding the pollution degree from romanian Black Sea coast. Farmacia 66(6), pp. 1059-1063
  12. Mititelu, M., Ioniţă, A. C., Moroşan, E. (2014). Research regarding integral processing of mussels from Black Sea. Farmacia, 62(3), pp. 625-632
  13. Ioniţă, A.C., Mititelu, M., Moroşan, E. (2014). Analysis of heavy metals and organic pollutants from some Danube river fishes. Farmacia 62(2), pp. 299-305
  14. Predescu, I., Miron, D., Parvu, C., Popescu, S. (2001). Studiul reologic asupra unor geluri cu diclofenac, Farmacia, 5, p.58-64
  15. Hîncu, L., Lupuleasa, D., Andrieş, A., Ordeanu, V., Mititelu, M., Mănesu, O. (2007). Studies regarding preparation and evaluation from ophthalmic therapeutic system of in situ gel forming systems with piroxicam, Farmacia, 5:557-568