Pharmaceutical Gels Formulation with Natural Extracts

MOROȘAN Elena1, MITITELU Magdalena1*, NICOLESCU Teodor Octavian2, NICOLESCU Florica3, NEACȘU Sorinel Marius1, IONIȚĂ Elena Iuliana4, POLL Alexandru5, OZON Emma Adriana6

1Clinical Laboratory and Food Hygiene Department, Faculty of Pharmacy, ”Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, 020956, Bucharest (ROMANIA)

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

3Toxicology Department, Faculty of Pharmacy, ”Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, 020956, Bucharest (ROMANIA)

4Pharmacognosy, Phytochemistry, Phytotherapy Department, Faculty of Pharmacy, ”Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, 020956, Bucharest (ROMANIA)

5Anatomy Department, Faculty of Dentistry, ”Carol Davila” University of Medicine and Pharmacy, 17-23, Calea Plevnei, 060015, Bucharest (ROMANIA)

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

*corresponding author: magdamititelu@yahoo.com

Abstract 

      In this work it was made four gels with carbopol 940 1% and tincture of Calendula in different concentrations: 1%, 3%, 5%, and 7%. The product resulted was analysed according to the present standards. It was analysed the characteristics, pH, stability and their spreadability for to select the optimal formulas. 

Keywords: gels, spreadability, tincture of calendula

Introduction

      Worldwide there is a growing interest of medical and pharmaceutical professionals in prevention and treatment of diseases with topical application, with semi-solid pharmaceuticals prepared from natural compounds [1,2,3]. The use of natural extracts in topical preparations has the advantage of a complex composition in active principles [4,5,6,7]. It is important that natural ingredients are not contaminated with various environmental pollutants [8,9]. Many natural extracts are also used for their systemic action, not only local, and are often preferred to the detriment of synthetic substances [10-15]. Hydrogels are made up of organic or inorganic macromolecular substances with the ability to hydrate by joining with water. Hydrogels have the following advantages: they are easily washable, they are preferable for people with oily skin, they have a good absorption capacity of active substances as well as a good penetration against oily bases. Carbopolies can be used to process non-greasy ointments, easily washable, stable, non-irritating to the skin and with rapid release. Several varieties of Carbopol are known: 940, 974, ULTREZ 10 [16,17]. To obtain the hydrogel, the carbopole is dispersed under stirring in a preservative solution, left to hydrate, then neutralized with a base (sodium, potassium, triethanolamine hydroxides), when the acid polymer passes into a soluble state. Mix slowly and complete with preservative solution. [16,18].

      Formulation characteristics, including viscosity, elasticity and rheology are the most important factors in the development and final behaviour of semisolid preparations [18,19].

Methodology

     The gels were prepared after formulas presented in Table 1, using an electrical agitator with 300 rpm.

     The spreading capacity of the gel formulations was measured 48 h after preparation by measuring the spreading diameter of 1 g of the gel between two 20 x 20 cm glass plates after 1 min. The mass of the upper plate was standardized at 125 g [20]. Weighs of 50 g, 100 g, and 250 g were subsequently placed over the sample at 1 min. intervals. The spreading areas reached by the sample were measured in millimetres in the vertical and the horizontal axes.

      The results were expressed in terms of the spreading area as a function of the applied mass according to the following equation:

Si = di2 (π / 4)

in which Si is the spreading area (mm2) resulting from the applied mass i (g) and di2 is the mean diameter (mm) reached by the sample.

The gels were also submitted at some control tests in order to determinate their characteristics and stability:

  • the determination of the appearance was made by examination with the magnifying glass (4.5x) of a sample stretched by thin layer on microscopic blade;
  • the determination of the main characteristics was made according to Romanian Pharmacopoeia X [21];
  • the pH was determined with Radelkis pH-meter;
  • the stability was made by maintaining the samples at 20C and 400C: 5g of sample were introduced into a weighing ampoule with lid, and then, the ampoule is maintained 8 hours at mentioned temperatures. Then, was examined the appearance of sample; 

Table 1. Gels composition

COMPONENTS FORMULA A  FORMULA B FORMULA C FORMULA D
Tincture of Calendula 1g 3g 5g 7g
Gel of carbopol 940 1% until 100g until 100g until 100g until 100g

Results 

      Results obtained at qualitative chemical analyze of Calendula tincture are presented in Table 2:

  Table 2. Qualitative chemical analyse of Calendula tincture

Analized fraction Active principle Results
Tanins + + +
Reactions on alcoholic solution Reductions compounds + + +
ODP + + +
Antracenozyds _
Cumaryns + 
Reactions on alcoholic hydrolized solution → etheric extract Carotenoyds _
Flavonozyds + + +
Sterolic heterozyds  _
Reactions on watery solution Poliuronyds + +
Amylum _

Fig. 1  Identification of active principles of Calendula tincture

Fig. 2  Base of carbopol gel and gels with tincture of Calendula 1%, 3%, 5% and 7%

Table 3. Gels characteristics

Characteristic Formula A Formula B Formula C Formula D
Initial macroscopic characteristics  appearance: homogenous;

colour:

yellowish;

smell: specific

 appearance: homogenous;

colour: yellow;

smell: specific

 appearance: homogenous;

colour: yellow-brown;

smell: specific

 appearance: homogenous;

colour: yellow-brown;

smell: specific
Macroscopic characteristics after 30 days  appearance: homogenous;

colour:yellowish

smell: specific

 appearance: homogenous;

colour: yellow;

smell: specific

 appearance: homogenous;

colour: yellow-brown;

smell: specific

 appearance: homogenous;

colour: yellow-brown;

smell: specific
Initial pH 5.5 – 6 5.5 – 6 5.5 – 6 5.5 – 6
pH after 30 days 5.5 – 6 5.5 – 6 5.5 – 6 5.5 – 6

  The data from Table 3 show that the gels are homogenous. All gels were presented a good stability by maintaining the homogenous appearance at 20C and 400C. A concentration in a tincture over 7% produce an un-homogenous appearance, the formulas became instable. We remark from Fig. 3 – 8 different values of spreading area of gels analysed due to their different consistency. The highest values have presented formulas B and C.

S (mm2)

Fig. 3  Spreading area function of the applied mass (carbopol gel 940 1%)

Fig. 4  Spreading capacity of gels test

S (mm2)

Fig. 5 Spreading area function of the applied mass for formula A

S (mm2)

Fig. 7 Spreading area function of the applied mass for formula C

S (mm2)

Fig. 8  Spreading area function of the applied mass for formula D

 

Conclusions

      In this work it was made four gels with carbopol 940 1% and tincture of Calendula in different concentrations: 1%, 3%, 5%, and 7%. 

      The experimental data show that the gels are homogenous. Moreover, the preparation has presented a good stability by maintaining the homogenous appearance at 20C and 400C. A concentration in a tincture over 7% produce an un-homogenous appearance, the formulas became instable. We remark from the graphics of spreading area different values of spreading area of gels analysed due to their different consistency. The highest values have presented formulas B and C.

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