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International Journal of Pharmaceutical Sciences

INT.J.PH.SCI.,MAY-AUG, 2010;2(2):551-555 ISSN 0975-4725 www.ijps.info

Original Research Manuscript


Jyotsana Madan*, Ramnik Singh** *Sinhgad College of Pharmacy, Vadgaon (Bk), Pune -41. **Khalsa College of Pharmacy, Amritsar-143002, Punjab, India Correspondence e-mail address: Ramnik Singh, Assistant Prof., Khalsa College of Pharmacy, Amritsar, E-mail : ramnik1144@yahoo.co.in, 09855007046, 09420148817- Jyotsana Madan*, Asst.Prof., jrmadan@hotmail.com

ABSTRACT Topical delivery systems of aloe vera gel were formulated using polymers like HPMC, Carbopol 934P, Methylcellulose and

Sodium alginate. The gels were evaluated for various physicochemical parameters like pH, viscosity, drug content and spreadability. In addition, in- vitro permeation studies through cellulose membrane and antimicrobial activity of the formulated gels was also performed. Formulations prepared using Carbopol934P shows desired properties and exhibit better release pattern. Keywords: Aloe vera, Carbopol 934P, methylcellulose, HPMC, sodium alginate, antimicrobial activity, in-vitro permeation study.

INTRODUCTION Gels are transparent to opaque semisolids containing gelling agent that merges or entangles to form a three-dimensional colloidal network structure. It is responsible for gel resistance to deformation and its visco-elastic properties.1 Gels have better potential as a vehicle to administer drug topically in comparison to ointment, because they are non-sticky, require low energy during formulation, are stable and have aesthetic value. Skin injuries (major and minor) or local infection can best be treated by application of product that form transparent water vapour and air permeable film over the skin surface from which the drug releases continuously from the application site.

plant. The gel has been reported to possess immunomodulatory, anti-inflammatory, antimicrobial, antifungal, UV protective, wound and burn healing promoting properties.2 Therefore, the present study was conducted to formulate a suitable topical

AVG gel formulation using different gelling agents like Carbopol 934P, HPMC, Methylcellulose and sodium alginate along with wheat germ oil as emollient. The prepared gels were evaluated for appearance, pH, content uniformity, viscosity, spreadability, invitro permeation study and antimicrobial activity.


Materials Aloe vera is a tropical or sub tropical plant of the genus aloe. The leaves which are lance-shaped with sharp points, contain an Plant material A. vera plants were collected(March 2003) and authenticated from Medicinal Plant Research and Development Centre, Govind Pant University of Agriculture and Technology, Pantnagar

essentially clear viscous gel known as aloe vera gel(AVG). It is the mucilaginous jelly obtained from the parenchyma cells of the

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(Uttarakhand), India. A voucher specimen (AV-8) has been retained in our museum for future reference. Chemicals Carbopol 934P, sodium alginate were purchased from Loba Chemie , HPMC (4000 cps), methycellulose from S.D. Fine

Appearance: The AVG gels having Carbopol 934P and HPMC were milky white and yellowish transparent respectively. Sodium alginate and methyl cellulose gels were opaque in appearance.

Determination of pH: The pH values(Table 2) of 1% aqueous solutions of the prepared gels were checked by using a calibrated digital pH meter (Sartorius, FEJ-100) at constant temperature.

Chemicals, Mumbai, cellulose membrane (Sigma Chemical Company, USA) and Agar from Hi-Media. All other chemicals used were of analytical grade and used as procured.

Drug content uniformity: The colorimetric determination of Methods Preparation of freeze dried Aloe vera gel: The inner mucilaginous parenchymatous tissues of leaves of aloe vera plants were separated out with the help of sterile knife. This mucilaginous, viscous parenchymatous tissue was homogenized in a blender at maximum 30 rpm. This homogenized mass was separated by G3 sintered glass filter with the help of vacuum and further freeze dried with the help of lyophilizer. The ratio of AVG and lyophilized powder was 40:1. glucomannan in the AVG was used as the method for The prepared gels determining drug content uniformity.3

equivalent to 2 mg of freeze dried aloe gel was weighed accurately and dissolved in 100 ml of distilled water and filtered. From this solution 0.4 ml was transferred to a 10 ml test tube. To this 4 ml of congo red reagent (0.01 %) was added with mild vortexing. The same mixture was left at room temperature for 20 min. Absorbance was measured at 540 nm wavelength. Amount of glucomannan was calculated by interpolating the standard curve(r2 =0.9747)

Development of gels: All the formulations were prepared using freshly boiled and cooled distilled water as per the composition listed in Table 1. Methyl and propyl paraben were dissolved in distilled water prior to the addition of the gelling agents. Carbopol gels were prepared by soaking Carbopol 934P in water and then neutralizing it with 18% w/v Sodium hydroxide. HPMC and methyl cellulose gels were prepared by dispersing the polymers in distilled water with continuous stirring and then warming it to get the gel. Gels containing sodium alginate were prepared by triturating and then soaking it in distilled water. The freeze dried aloe vera gel, the wheat germ oil and disodium EDTA were incorporated with trituration, after partial gelling was accomplished. Spreadablity: Spreadability of the formulation was determined by an apparatus(slightly modified) suggested by Mutimer et al.4 It consists of a wooden block and provided with a pulley at one end. A rectangular ground glass plate was fixed on the wooden block. Excess of gel (about 2gm) under study was placed on this ground glass plate, and then the gel was sandwiched between this plate and another glass plate having the dimensions of the ground glass plate attached with a hook. A 300 gm weight was placed on the top of the two plates for 5 minutes to expel air and Evaluation of formulated gels: Prepared AVG gels were to provide a uniform film of the gel between the plates. Excess of the gel was scrapped off from the edges. The top plate was then subjected to a pull of 30 gm with the help of a string attached to the hook and the time (in second) required by the top plate to cover a distance of 10cm was noted. The spreadability was calculated using the formula : Viscosity: Viscosity was measured by placing 100 gm sample (allowed to settle for 5 mins) in sample holder of Brookfield viscometer [ Spindle no. 6 at 10 rpm].

evaluated for appearance, pH, drug content uniformity, viscosity, spreadability, permeability studies and antimicrobial activity. All the gels were visually inspected for clarity, colour homogeneity, presence of particles and fibers.

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S=ml/t, where, S=Spreadability, m=Weight tied to the upper glass slide, l=length of the glass slide and t=time taken in seconds.

The various parameters evaluated for gels are represented in Table 2. The pH of all gel formulations was found between 6.97.3, which lies in normal pH range of the skin. All the prepared gel formulations showed uniformity in drug content

In-vitro skin permeation study: This study was done using the Keshary-Chien diffusion cell5. Cellulose membranes were used as permeation barrier. The gel sample was placed on the donor

(glucomannan) and were within permissible range indicating the uniformity of drug dispersion in the gels. In antimicrobial study, percentage inhibition was taken as measure of antimicrobial activity. All the formulations exhibited antimicrobial activity against S.aureus and E.coli.(Table:3) Viscosity is an important parameter for characterizing the gels as it affect the spreadability and release of the drug. 7 The addition of disodium EDTA is essential for an aloe vera gel formula in order to help prevent viscosity loss caused by metallic cations and ions which are present in the aloe. This is particularly important for a clear product that may be exposed to heat and sunlight.8 The viscosity was decreasing in the order of alginate. Spreadability is the

compartment and covered with aluminium foil to prevent drying. The receptor compartment was filled with the receptor phase (degassed,de-ionised water).The temperature of receptor phase was maintained at 37 1C. throughout the experiment. The compartment was in contact with ambient condition of environment. The amount of drug permeated through the membrane was determined by withdrawing samples at

predetermined time intervals for 12 hours and replacing with the same volume of prewarmed (37 1C) receptor solution to maintain sink conditions. The samples were analysed for amount of glucomannan. Blanks are run for each set as described above with placebo gel and calculated accordingly.

HPMC<Carbopol<Methylcellulose<Sodium AVG(H)<AVG(C)<AVG(M)<AVG(A)}

parameter which will help in the uniform application of gel to the skin. A good gel takes less time to spread and will have high

Antimicrobial activity : Antimicrobial study of the formulated gels was conducted by ditch plate technique.6 It is a technique used for evaluation of bacteriostatic and fungistatic activity of a compound and is mainly used for semisolid formulations. Agar plates were prepared and sterilized as per standard procedure. A ditch (2.5x0.5cm) was made in the centre of agar plate and was filled by test formulations (0.5gm). The prepared culture loops (E.coli, S. aureus) were streaked across the agar at a right angle fro the ditch to the edge of the plate. A standard containing gentamycin and control plates containing gel without AVG

spreadability. The spreadability of formulated gels was found to decrease with increase in viscosity. The major component of freeze dried aloe vera gel are Aloe polysaccharides have


shown to exhibit other biological activities and act synergistically with other compounds in aloe.9 In vitro permeation of glucomannan from all prepared gel formulation was found to be slow and extended over a 12 hour period. The permeation rate was in the order of Carbopol> HPMC>Methylcellulose>Sodium alginate gel as shown in Figure 1. The highest permeation of glucomannan from carbopol gels (85.42%) could be attributed to more swellability of carbopol when compared to the other polymers. The basic invitro data was plotted according to

were also prepared. After incubation for 18-24 hours at 25 C, the bacterial growth was observed and the percentage inhibition was measured as follows : % Inhibition=L2 /L1x100, where, L1=Total length of the streaked culture, and L2=Length of inhibition.

Higuchis equation and the plots were found to be fairly linear with their high regression coefficient(r2=0.976-0.941) indicating diffusion controlled mechanism.10 The results reveal that the total

Results and Discussion

amount of glucomannan permeated from the formulations was dependent on the nature of the polymer used, viscosity as well as the consistency of the formulations. Based on the

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physicochemical properties and drug release, Carbopol 934P was found to be a suitable gelling agent for AVG.

antimicrobial activity of these gel formulations is comparable to the standard. These results suggest the feasibility of the topical gel of aloe vera. However preclinical studies of these

CONCLUSION Aloe vera topical gels were developed using various polymers. All the gels showed good physico-chemical properties. The

formulations needs to be done.

Table 1: Composition of gel formulations of Aloe vera S. No Ingredients AVG(C) AVG(H) AVG(M) AVGA(A) 2.5 8 0.2 1 0.2 0.1 100

1. Aloe vera gel* (g) 2.5 2.5 2.5 2. Carbopol 934P (g) 0.8 3. Sodium hydroxide** (ml) q.s 4. HPMC(4000 cps)*** (g) 3.5 5. Methyl Cellulose (g) 5.0 6. Sodium alginate (g) 7. Disodium EDTA (g) 0.2 0.2 0.2 8. Wheat germ oil (g) 1 1 1 9. Methyl paraben (g) 0.2 0.2 0.2 10. Propyl paraben (g) 0.1 0.1 0.1 11. Distilled water (q.s) (g) 100 100 100 *Freeze dried, **18%w/w solution; ***Hydroxy Propyl Methyl Cellulose; AVG= aloe vera gel.

Table 2: Evaluation of gel formulation of Aloe vera

Formulation Code pH* AVG(C) AVG(H) AVG(M) AVG(A) 7.3+0.02 7.2+0.03 7.1+0.02 6.9+0.01 97.60 +0.45 93.31 +0.32 94.90 +0.23 96..40 +71 Parameters Glucomannan content %* Viscosity (cps)* 16820 +150 14680 +125 19980 +150 24770 +100 Spreadability 11.68 12.98 9.88 8.34

*Values are mean + S.D, n; 3

Table 3: Antimicrobial activity of Gel Formulations and Gentamycin gel Formulations Gentamycin gel AVG(C) AVG(H) AVG(M) AVG(A) *Values are mean + S.D, n= 3 Mean zone of inhibition (mm)* (n=3) S. aureus E. coli 30+0.1 25+0.2 19+0.1 23+0.1 22+0.2 200.2 180.2 170.1 140.1 90.2

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100 80 60 40 20 0
0 2 4 6 Time (Hours) 8 10 12

Cummulative % permeated



Methyl cellulose
Figure: 1

Sodium Alginate

1) Lorraine Pena G, Gel dosage forms, Theory formulation and Processing, The Upjohn company Kalamazoo, Michigan, 38187. 2) Grindlay D, Reynolds T, The Aloe vera phenomenon: A review of the properties and modern uses of the leaf parenchyma gel, J Ethnopharmacol,16,1986, 117-151. 3) Eberendu AR, Luta G, Edwards JA, McAnalley BH, Davis B, Rodriguez S, and Henry CR , Quantitative colorimetric analysis of aloe polysaccharides as a measure of Aloe vera quality in commercial products, J AOAC Int, 88,2005 , 684-691. 4) Mutimer MN, Riffikin C, Hill J A, Modern ointment base technology. II. Comparative evaluation of bases, Am. Pharm. Assoc.,45, 1956, 212-218 5) Keshary P R, Chien Y W, Mechanism of Transdermal


Eshun K, He Q. Aloe vera: a valuable ingredient for the food, pharmaceutical and cosmetic industries--a review, Crit Rev Food Sci Nutr, 44, 2004, 91-96.

10) Higuchi WI. Analysis of data on the medicament release from

ointments, J Pharm Sci. 51, 1962, 802-804.

Article History: Date of Submission: 13-02-2010 Date of Acceptance: 10-05-2010 Conflict of Interest: NIL Source of support: NONE

Controlled Nitroglycerin Administration (II) Assessment of Rate-Controlling Steps, Drug Develop Ind Pharm,10, 1984,1663 -1699. 6) Hugo WB, Russell AD. Pharmaceutical Microbiology. Oxford, UK:Blackwell Scientific Publications, 1977,190. 7) Yonese,M. Sustained drug delivery by gels.In OsadaY.K.,ed.Gels Handbook.Vol3.SanDiego,CA,Academic Press:2001,230-240. 8) www.noveon.com

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