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Design, formulation and evaluation of Aloe vera chewing gum
Abolfazl Aslani1, Alireza Ghannadi2, Razieh Raddanipour1
1 Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Cente, Isfahan, Iran
2 Department of Pharmacognosy, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| Date of Submission | 10-Jul-2014 |
| Date of Acceptance | 02-Feb-2015 |
| Date of Web Publication | 31-Aug-2015 |
Correspondence Address:
 Source of Support: Vice Chancellery of Research and Technology of Isfahan University of Medical Sciences., Conflict of Interest: There are no conflicts of interest.  | Check |
DOI: 10.4103/2277-9175.163999
Background: Aloe verahas antioxidant, antiinflammatory, healing, antiseptic, anticancer and antidiabetic effects. The aim of the present study was to design and evaluate the formulation of Aloe verachewing gum with an appropriate taste and quality with the indications for healing oral wounds, such as lichen planus, mouth sores caused by cancer chemotherapy and mouth abscesses as well as reducing mouth dryness caused by chemotherapy.
Materials and Methods: In Aloe verapowder, the carbohydrate content was determined according to mannose and phenolic compounds in terms of gallic acid. Aloe verapowder, sugar, liquid glucose, glycerin, sweeteners and different flavors were added to the soft gum bases. In Aloe verachewing gum formulation, 10% of dried Aloe veraextract entered the gum base. Then the chewing gum was cut into pieces of suitable sizes. Weight uniformity, content uniformity, the organoleptic properties evaluation, releasing the active ingredient in the phosphate buffer (pH, 6.8) and taste evaluation were examined by Latin square method.
Results: One gram of Aloe verapowder contained 5.16 ± 0.25 mg/g of phenolic compounds and 104.63 ± 4.72 mg/g of carbohydrates. After making 16 Aloe verachewing gum formulations, the F16 formulation was selected as the best formulation according to its physicochemical and organoleptic properties. In fact F16 formulation has suitable hardness, lack of adhesion to the tooth and appropriate size and taste; and after 30 min, it released more than 90% of its drug content.
Conclusion: After assessments made, the F16
formulation with maltitol, aspartame and sugar sweeteners was selected as the best formulation. Among various flavors used, peppermint flavor which had the most acceptance between consumers was selected. Keywords: Aloe verachewing gum, lichen planus ulcer, mouth ulcers, phenolic compounds, wounds caused by cancer chemotherapy
How to cite this article:
Aslani A, Ghannadi A, Raddanipour R. Design, formulation and evaluation of Aloe vera chewing gum. Adv Biomed Res 2015;4:175 |
| Introduction | |  |
The scientific name of Aloe verais Aloe barbadensis Miller. This plant belongs to the Liliaceaefamily.[1] There are more than 300 species of plants which are used for therapeutic, cosmetic and nutraceutical purposes.[2]Aloe verais separated to latex and gel products. Aloe veralatex, which is the bitter yellow extraction, comes from pericyclic tubules of the outer skin leaf. Aloe veracolorless gel is extracted from inner fresh leaf.[3]Aloe verais orally used to control digestive problems, including constipation, anorexia, irritable bowel syndrome and colitis, asthma, diabetes and strengthening the immune system. It is also topically used to treat eczema, burns, acne, dermatitis and psoriasis. It stimulates cell regeneration. Aloe veracontains various compounds such as vitamins, sugars, enzymes, minerals, lignin, saponins, salicylic acids, amino acids and anthraquinone.[1],[4]
The healing properties of Aloe veraimprove the skin which is exposed to ultraviolet (UV) and gamma rays. It has antiinflammatory, antiseptic, antiviral, antibacterial, antitumor, moisturizing, antiaging, hypoglycemic, antidiabetic, cytotoxic, and antioxidants effects. It is also used against cardiovascular diseases.[5]
In recent decades, the scientific studies on Aloe veradue to the above mentioned properties have attracted more attention.[6] Researchers have greatly proven therapeutic claims about Aloe verasince 1986.[7]Aloe verahas been used for therapeutic purposes in many cultures, such as Greece, Egypt, Mexico, India, China and Japan for 1000 of years.[5]
Several products containing Aloe verainclude juices, gel capsule, pills, creams, lotions, soaps, shampoos, toothpaste, mouthwash, hair styling, body shampoos, hand washing liquids and etc., have been marketed.[8]
Pharmaceutical chewing gums are produced in a solid form and a single dose. Their base mainly consists of gum base. This form of medication contains one or more active ingredients that are released by chewing. Pharmaceutical applications of pharmaceutical chewing gums include topical treatment of oral diseases and systemic delivery after absorption through the buccal mucosa or the gastrointestinal route.[9]
The benefits of chewing gum include consumption without water,[10] high acceptance by children,[10] low side effects, suitable stability,[11] high bioavailability, rapid onset effect[10] and relieving the mouth dryness by stimulating saliva.[10],[12]
Formulation of pharmaceutical chewing gums contain pharmaceutical active ingredients, gum bases, fillers, elastomers, plasticizers, softeners, emulsifiers, sweeteners and flavors.[13] Factors affecting drug release in this type of dosage form include physicochemical properties of the active ingredient, chewing gum properties and related factors with strength and number of masticatory movements.[10],[14]
Some of the formulated drugs in the form of chewing gum include fluoride, chlorhexidine, nicotine, aspirin, caffeine, and dimenhydrinate.[15]
It has been reported that some active principles of Aloe verahave antiinflammatory and wound healing effects in some of the phases of the inflammation. The polysaccharide of aloe mucilage gel is determined as active ingredient for antiinflammatory effects and has an immunomodulatory role.[16] Thus, according to what was mentioned, oral Aloe veracan be used as a wound healer for oral wounds.
To heal mouth sores, such as lichen planus, ulcers and abscesses caused by cancer chemotherapy, oral products such as mouthwash are used. Recently, one study examined the effects of 70% Aloe veraextract in the form of mouthwash for the treatment of mucositis caused by radiotherapy[17] and another study examined the effects of 80% Aloe veraextract in the form of mouthwash to treat lichen planus.[18]
The aim of this study was to design and to evaluate the formulation of Aloe verachewing gum with an appropriate taste and quality with the indications for healing oral wounds, such as lichen planus, mouth sores caused by cancer chemotherapy and mouth abscesses as well as reducing mouth dryness caused by chemotherapy.
| Materials and Methods | | |
Materials
Aloe verapowder was provided from Barij Essence Pharmaceutical Company (Isfahan, Iran). Gum bases of elvasti, 487, stick, fruit C were provided from Gilan Ghoot Company (Rasht, Iran). Flavors of eucalyptus, peppermint, banana, cola and cinnamon were provided by Goltash Company (Isfahan, Iran) and cherry flavor from Farabi Pharmaceutical Company (Isfahan, Iran). Glycerin, aspartame, maltitol, xylitol, anthrone reagent, sulfuric acid, chloroform, Folin–Ciocalteu's phenol reagent, gallic acid and sodium carbonate were purchased from Merck Company (Germany).
Methods
Determination of carbohydrates by mannose
To determine the amount of carbohydrates by mannose, a colorimetric method was applied using anthrone. Anthrone reagent prepared by dissolving pure anthrone in concentrated sulfuric acid and mannose was used as the standard material. Reagent was poured into a test tube with cap, and then the tube was placed in an ice water bath. After cooling, the sample solution was slowly poured over it and was thoroughly mixed for 5 min. Then it was placed in boiling water bath for 10 min and immediately the test tube was entered in ice-cold water bath, then the absorption was read against a control in wavelength of 623.2 nm.[19]
Determination of phenolic compounds
Folin–Ciocalteu method which is a colorimetric assay was used to determine the polyphenol content of a substance. Gallic acid was used as a standard phenol. The sample solutions were poured into a test tube and after adding water, Folin–Ciocalteu's phenol reagent was added and shaken completely. Wait 30 s to 8 min and then a solution of sodium carbonate is added and well shaken. The tubes were maintained for 2 h at 20°C (or 30 min at 40°C) and after that absorption for each solution was read at a 765 nm wavelength and by using the data, absorption curve was plotted against concentration.[19],[20],[21]
Preparation of Aloe vera chewing gum
Aloe verachewing gum was formulated using a mixture of gum bases, sugar, liquid glucose, glycerin, sweeteners (xylitol, maltitol, aspartame) and flavors such as eucalyptus, peppermint, cola, banana, cinnamon and cherries.
In formulation of Aloe verachewing gum, 10% of Aloe veradried extract is entered into the gum bases.
The gum base mixture is softened at the temperature of 70°C. Aloe verapowder, sugar, liquid glucose, glycerin and other ingredients are added to the base. Finally, at the temperature of 40°C, flavors were added and the mixture of chewing gum was cut into pieces of appropriate sizes [Table 1]. | Table 1: Formulations of Aloe vera chewing gum with different ingredients
Click here to view |
The best formulation in terms of organoleptic properties was selected and the flavors of eucalyptus, mint, cola, banana, cinnamon and cherry were added to it and the best among them was selected [Table 2]. | Table 2: Formulations of Aloe vera chewing gum by altering the flavoring agent in the formulation F16
Click here to view |
Weight variations
Twenty chewing gums from each formulation were weighed. Mean and standard deviation of the weights were calculated.[9]
Content uniformity
Ten chewing gums were randomly selected.[9] At first, the chewing gum was dissolved in chloroform. Then the phosphate buffer with (pH, 6.8) was used to extract the drug into the aqueous phase. The carbohydrates value was measured on the amount of mannose absorption in the 623.2 nm by UV spectrophotometer.
Drug release
In order to study drug releasing from the gum base European Pharmacopoeia has suggested the device that simulates the act of chewing.[22] The device includes the following sections: The device includes a piston to enter the stroke, a chamber including the medium and chewing gum, circulation pipe with 37°C water around the chamber in order to provide oral temperature, engine and water bath.[23]
One milliliter of the sample was removed from the chamber at 5, 10, 15, 30, 40 min by pipette and 1 mL of phosphate buffer (pH, 6.8) at 37°C was added to the chamber. A placebo chewing gum (without medication) was also placed on the masticatory apparatus. And at the mentioned time they were sampled. The absorption was measured in 623.2 nm. This experiment was repeated 3 times for each formulation.
Evaluation of the organoleptic properties of the Aloe vera chewing gum
In order to evaluate the organoleptic properties of Aloe verachewing gum that contains hardness and softness, suitable mass volume, lack of stickiness to the teeth and suitable taste, samples with different combining base, sweeteners and flavors were prepared and in the first phase were tested by volunteers. Thus, in the first phase the 10 volunteers were asked to chew gum for 20 min and tell their comments about the hardness and softness, lack of stickiness to the teeth, volume and taste of the chewing gum.
Flavor evaluation of the Aloe vera chewing gum
Different flavors were added to the best formulation in terms of organoleptic properties. According to the Latin square method, based on the panel test, 20 people were volunteers and asked their opinions about different flavors. Two superior flavors were given to 30 other volunteers to choose the best one.
Evaluation of mechanical properties of the Aloe vera chewing gum
Tensile test was used for F16, F17 and F18 formulations with different bases by universal testing machine (STM, Santam, Iran). Each sample of gum in the form of a dumbbell with 13 mm width and 3 mm thickness were prepared and with 30 mm gauge space, tensile test was performed. The tension velocity for samples was 50 mm/min.
| Results | | |
Analysis of the Aloe vera powder
One gram of Aloe verapowder contained 5.16 ± 0.25 mg/g of phenolic compounds and 104.63 ± 4.72 mg/g of carbohydrates.
Analysis of the Aloe vera chewing gum
Uniformity of content for F16 formulation, which was selected as the best formulation, was 10.68 ± 1.69 mg according by mannose and its weight variation was 903.10 ± 4.92 mg.
Releasing of carbohydrates based on mannose from formulations with different gum bases ratios and different sweeteners were shown in [Figure 1] and [Figure 2] respectively. As can be observed, after 30 min, about 90% of the drug content of the formulations was released. | Figure 1: In vitro release of Aloe verachewing gum formulations with various gum bases according to mannose in pH, 6.8 phosphate buffer at 37°C
Click here to view |
 | Figure 2: In vitrorelease of Aloe verachewing gum formulations with various sweeteners according to mannose in pH, 6.8 phosphate buffer at 37°C
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The organoleptic properties of Aloe verachewing gum depend on using excipients. The F16 formulation had the highest acceptance according to the hardness and softness properties, lack of stickiness to tooth, volume and taste [Table 3]. | Table 3: The averages of scores allocated by volunteers for organoleptic properties of Aloe vera chewing gum formulations by 10 volunteers
Click here to view |
The F16 formulation which was prepared with different flavors that mint and cinnamon (F22, F23) had the highest approval rating among volunteers [Table 4]. Of these two flavors, the mint flavor (F22) won the most points [Table 5]. | Table 4: The scores allocated by 30 volunteers for each taste of best Aloe vera chewing gum formulations
Click here to view |
 | Table 5: The scores allocated by 30 volunteers for top tastes of best Aloe vera chewing gum formulations
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The results of the tensile test for F16, F17 and F18
formulations with different ratios of the gum bases were shown in [Figure 3]. | Figure 3: Tensile behavior of F16, F17, and F18 formulations with various gum bases
Click here to view |
| Discussion | | |
Due to the properties of Aloe vera, aloe chewing gum can be formulated as a medication for oral wound healing.
In present study, in comparison with mouthwash form it was preferred to use chewing gum (as a drug delivery system) due to: More attractive and easier usage for the convenience and hold of increased consumption, more safety, lower overdose risk, releasing drug within a longer time (for the mouthwash about 30 s and for the chewing gum about 30–45 min) and controlled releasing of the drug.[24]
Kolahi-Kazerani et al. reported that the profile of the drug releasing in form of the chewing gum was appropriate and this form was considered as a better choice than mouthwash form because of above reasons.[24]
One gram of Aloe verapowder contained 5.16 ± 0.25 mg/g of phenolic compounds and 104.63 ± 4.72 mg/g of carbohydrates.
In Cockand Ruebhart study, the carbohydrates content and phenolic compounds were reported 201 mg/g and 46.8 mg/g respectively.[19] The differences between the values obtained in our study and the mentioned article can be due to different sources of Aloe A. vera, plant growth conditions, the method of preparing powders, the extraction type and the measurement methods.
In the preparation of Aloe verachewing gum, four gum base types were used. The gum bases of elvasti, 487, stick and fruit C have different hardness. Elvasti and 487 compared with the stick and fruit C are more rigid. The hardness and softness of each chewing gum can be set by changing the amount of these bases to select the best formulation in terms of hardness and softness. Among F1 to F6 formulations, F6 formulation had better organoleptic properties [Table 1]. Because of this advantage, F6 formulation was selected to continue and formulations of F7 to F16 were made by the same percentage. In this study for the preparation of Aloe verachewing gum formulations, Aloe verapowder, sugar, maltitol, xylitol, aspartame, liquid glucose, glycerol and various flavors with the specified percentages were added to the gum bases. Using a combination of sweetener such as xylitol, maltitol and aspartame along with sugar was useful. The F16 formulation prepared by combining sweeteners including sugar, aspartame and maltitol was the best formulation of flavors. Theresa Cea and Glass study showed that the aspartame in chewing gum increased the stability of the sweet flavour.[25]
In order to find the effects of flavors on the organoleptic properties, in general, the flavors had the effects of softening on the formulation. Pepperint, cinnamon, cherry, cola, banana and eucalyptus flavors were used and among them mint had the greatest acceptance among the volunteers.
Aslani and Jalilian prepared the caffeine chewing gum and in their study the volunteers were selected cinnamon flavor as the best one.[26]
On the other hand, in another study which was conducted by Aslani and Rafiei to make the nicotine chewing gum, cherry and eucalyptus flavors were selected as the best flavors.[23]
In another study by Aslani et al., to make green tea chewing gum, mint and cinnamon flavors were selected by volunteers.[27]
Since the test for uniformity of content and the acceptable range of it for pharmaceutical chewing gum are not available specifically, therefore, the uniformity of content test for the tablet by European Pharmacopoeia test was used to examine the content uniformity of Aloe verachewing gum. Content uniformity test was separately carried out on 10 samples of F16
formulation. The mean of carbohydrate concentration was calculated in terms of mannose. According to the results, the content uniformity was in the acceptable range.
Pharmaceutical chewing gums are formulated in such a ways that release the maximum of its active ingredient at the appropriate time. Factors such as speed and the intensity of chewing and the amount of saliva production affect the releasing and absorption of oral drugs.[12]
Drug releasing rate from pharmaceutical chewing gum depends on their dissolution in water. Soluble substances in water are rapidly, and sparingly dissolve but insoluble substances in water are slowly released from the pharmaceutical gum bases.[28]
In releasing test of samples with different percentage of gum bases [Figure 1], we observed that chewing gum samples with a higher percentage of softer bases (F17
) had more releasing amount in compare with F16
and F18 with a lower percentage of softer bases at the same time. In contrast, the releasing of F18 sample which had a higher percentage of the hard bases was less than the other two samples at the same time.
As seen in [Figure 2], the amount of sample releasing with different types of sweeteners was almost identical.
In the present study, the releasing of carbohydrates by mannose after 30 min, from chewing gums with different bases such as F16, F17 and F18
were 92%, 96% and 85% respectively. In F6, F15 and F16 chewing gums with different sweeteners over than 90% of carbohydrate were released after 30 min.
In the study conducted by Aslani and Jalilian, the release of caffeine in chewing gum at 10, 20 and 30 min were reported 55%, 78% and 89% respectively.[26]
Also, in the study conducted by Aslani and Rafiei, the release of nicotine from 2 to 4 mg chewing gums at 20 min was reported 83% and 79% respectively.[23]
By examining the graph of stress strain of F16, F17 and F18 formulations with different bases composition, as can be seen in [Figure 3], all three formulations had the linear elastic behavior because of the effect of strain. By increasing the strain, it entered the linear area, and then by increasing the strain, the yield point was reached. Then, by increasing the strain, the samples showed plastic behavior and before reaching the stage of hardening because of the stress the rupture occurred. The F18 formulation containing higher elvazti and 487 bases had higher yield point than the other two formulations and the F17 formulation containing higher stick and fruit C bases had lower yield point than the other two formulations. It is expected that the F18 chewing gum due to the higher yield point is more lasting during the chewing and because of long linear region is more elastic. However, the F17 formulation due to lower yield point loses the ability of chewing in the mouth sooner and by considering the short linear region has a greater plasticity and the F16 formulation behaves intermediately. The results of the study conducted by Aslani et al.support the results obtained in this study.[27]
| Conclusion | | |
According to the findings of the present study, Aloe verachewing gum can be formulated with appropriate organoleptic properties and the best formulation considering the organoleptic properties was F16 formulation. Based on the views of participants, from six flavors which tested atfirst mint and cinnamon were selected as better flavors and in next stage between these two mint was chosen as the best flavoring agent.
Acknowledgment
This study was supported by Isfahan University of Medical Sciences as a thesis research project numbered 392035.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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