International Journal of Research in Pharmacology & Pharmacotherapeutics

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1 International Journal of Research in Pharmacology & Pharmacotherapeutics ISSN Print: IJRPP Special Issue 1 Oct - Dec ISSN Online: Journal Home page: Research article Open Access Formulation and characterization of aloe emulgel using rice hulls as an excipient A. Sumathi*, TNK. Suriyaprakash Department of Pharmaceutics, Al Shifa College of Pharmacy, Perinthalmanna, Malappuram, Kerala, Pin *Corresponding author: A. Sumathi venisumathi@gmail.com ABSTRACT The combustion of rice hulls yields rice husk ash (RHA) which is a potential source of amorphous reactive silica (83 90%). This has got a variety of applications in various fields of pharmaceuticals, material science and technology. Silicon strengthens the hair and renders it less brittle for splitting. At optimum silicon uptake the skin and hair is well hydrated and maintain a lusture that is attractive and young looking. The literature review reveals the traditional use of Aloe barbadensismiller (Ab) for hair growth and for improvement in hair growth following alopecia. Thus an attempt was made to develop an emulgel for hair care with the combined effect of silica in RHA and Ab. Preformulation studies revealed that the drug component, silica, polymers and other excipients were compatible with each other. Different formulations containing 1% silica using emulsifying agents (Tween 20/Span 20) and gelling agents (Carbopol/HPMC) in various ratios were prepared and characterized by analyzing their physicochemical and rheological parameters viz. appearance, extrudability, ph, spreadability, viscosity, globule size and distribution. The mean globule size and poly dispersity index were found to be 2417 nm and respectively. The skin irritation test for the optimized formulation was performed on healthy albino rats had shown no erythema, edema or reddening of skin. The stability studies were carried out as per ICH guidelines which indicated no significant change in their rheological parameters, drug content and globule size. Thus, it was concluded that silicon dioxide obtained from rice husk ash can be used as an excipient in formulating hair care products which also supports technological and economical points of view. Keywords: Aloes, Emulgel, Hair-care, Rice hull. INTRODUCTION Excipients have been seen as among the primary stumbling blocks for formulating active pharmaceutical ingredients (API), dietary supplements and processing of food materials. Excipients are defined, by the International Pharmaceutical Excipients Council, as substances apart from the active drug or pro-drug which has been properly evaluated for safety and is included in a drug delivery system to either aid processing of the system during manufacture, protect, support or ~ 24~

2 enhance stability, bioavailability or patient acceptability; assist in product identification; enhance any other attribute or overall safety and effectiveness of the product during storage and use [1]. Excipients aid in designing formulation and thereby help us to obtain the desired properties for the finished products. There has been trendy shifts from the use of synthetic materials to renewable resources like herbs. Also waste management like recycling and semi synthetic approaches like partial chemical synthesis, compounds isolated from natural sources (e.g. plant material or bacterial or cell cultures) as starting materials. From a synthesis point of view, it is very tedious to obtain a biosynthesizing structurally complex chemical compound [2, 3]. Thus, using a small agricultural investment, a plant can be grown to produce chemicals/chemical intermediates that can synthesis would be utilized for a variety of industrial applications. The waste materials after the generation of primary products are intended for disposal. The cultivation and collection of paddy produces large amount of wastes in terms of rice hulls. This agricultural waste produced in a particular period of the year pose potential pollution problem and therefore an efficient utilization and transformation, to excipient, is of great importance which not only for minimizes environmental pollution but also for gains higher profit. RHA contains high quantities of silicon dioxide (SiO 2 ). This component is used for different purposes, such as the production of Portland cement, optical fibers for telecommunication, primary raw material for many ceramics such as earthenware, stoneware, and porcelain, sand casting, primary component of diatomaceous earth, manufacturing of photovoltaic cells, additive in the production of foods, as a flow agent in powdered foods or to adsorb water in hygroscopic applications, used as a wine, beer, juice fining agent, as filler material in paints and polymers industry [4]. Hydrophobic silica is used as a defoamer component. In hydrated form, it is used in toothpaste as a hard abrasive to remove tooth plaque. A silica-based aerogel was used in the Stardust spacecraft to collect extraterrestrial particles. Silica is also used in the extraction of DNA and RNA due to its ability to bind to the nucleic acids under the presence of chaotropes. In cosmetics, it is useful for its light-diffusing properties and natural absorbency. It is also used as a thermal enhancement compound in ground source heat pump industry [5, 6]. Colloidal silicon dioxide is used in the pharmaceutical industry to stabilize emulsions, as thixotropic agent, thickening and suspending gels, in the preparation of semi-solid, being used in concentrations ranging from 0.5 to 20%. Aloe vera belonging to the Lily (Liliaceae) family is a perennial succulent plant. This miracle plant has been used for traditional medical purposes in several cultures for millennia. It has been demonstrated that Aloe vera has growth promoting activities [7, 8]. It repairs dead skin cells on the scalp. It also acts as a great conditioner and leaves the hair very smooth and shiny. It promotes hair growth, prevents itching on the scalp, reduces dandruff and conditions the hair. It is rich in amino acids, vitamin A, folic acid and vitamin C [9, 10]. Topical preparations are used for the localized effect at the site of their application by virtue of drug penetration into the underlying layer of skin or mucous membrane. Over the last decades the treatment of illness has been accomplished by administrating drug to human body via various routes namely oral, sublingual, rectal, parental, topical, inhalation etc. Topical delivery can be defined as the application of a drug containing formulation to the skin to directly treat cutaneous disorders (e.g. acne) or the cutaneous disorders (e.g. psoriasis) with the intent of containing the pharmacological or other effect of the drug to the surface of the skin or within [11, 12, 13]. The combination of hydrophilic cornified cells in hydrophobic intercellular material provides a barrier to both hydrophilic and hydrophobic substances [14]. Within the major group of semisolid preparations, the use of transparent gels has expanded both in cosmetics and in pharmaceutical preparations. In spite of many advantages of gels a major limitation is in the delivery of hydrophobic drugs. So to overcome this limitation an emulsion based approach is being used so that even a hydrophobic moiety can enjoy the unique properties of gels. When gels and emulsions are used in combined form the dosage forms are referred as Emulgel [15, 16]. In recent years, there has been great interest in the use of novel polymers with complex functions as emulsifiers and thickeners because the gelling capacity of these compounds allows the formulation of stable emulsions and creams by decreasing surface and interfacial tension and at the same time increasing the viscosity of the ~ 25~

3 aqueous phase[17, 18, 19]. In fact, the presence of a gelling agent in the water phase converts a classical emulsion into an emulgel. Both oil-in-water and water-in-oil emulsions are used as vehicles to deliver various drugs to the skin [20, 21, 22]. Emulsions possess a certain degree of elegance and are easily washed off whenever desired. They also have a high ability to penetrate the skin. Emulgels for dermatological use have several favorable properties such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, nonstaining, water-soluble, longer shelf life, bio-friendly, transparent & pleasing appearance [23, 24]. The present investigation is carried out with an aim to formulate a hair care emulgel using Aloe vera and silica extracted from rice husk ash; and to evaluate its physicochemical, rheological parameters and shelf life. MATERIALS AND METHODS The plant Aloe Barbadensis Miller (Family: Liliaceae), selected for the proposed study was collected from Kalady, Ernakulam District Kerala state, India. Aloe vera gel is the mucilaginous jelly obtained from parenchyma cells of the Aloe vera plant. When exposed to air, the gel rapidly oxidizes, decomposes and looses much of its biological activities. The entire process involves washing the freshly harvested Aloe vera leaves in water. In order to avoid contamination of internal fillet with the yellow sap, the traditional hand-filleting method of processing Aloe leaves was developed. In this method, the lower 1 inch of the leaf base (the white part attached to the large rosette stem of the plant), the tapering point (2-4 inch) of the leaf top and the short, sharp spines located along the leaf margins are removed by a sharp knife, then the knife, is introduced into the mucilage layer below the green rind avoiding the vascular bundles and the top rind is removed. The bottom rind is similarly removed and the rind parts, to which a significant amount of mucilage remains attached, are discarded. It was peeled and scooped out the gel with a spoon. Finally it was placed into a blender, then transferred into a sterilized clean glass jar and stored in the refrigerator. The rice hull ash selected for the proposed study was collected from a rice milling industry in Ernakulam district, Kerala, India. The selection of ash is important as the quality of ash determines the total amount as well as quality of silica recoverable. Ash which has undergone maximum extent of combustion is highly desirable as it contains higher percentage of silica. It appears white-grey in color when compared to the black colored ash obtained from incomplete combustion. The carbon present in such ash hinders the main silica digestion reaction and may change the product characteristics. The foreign matter and other residual materials are removed carefully from the ash. In first step, the silica in the ash gets extracted with caustic soda at specific conditions to form sodium silicate solution. After completion of digestion process, the solution was filtered to remove any residual undigested ash content. And the clear filtrate is taken for precipitation process which was taken place in the precipitator. Dilute sulphuric acid at a specific flow rate is passed through the silicate solution with continuous stirring. Then the precipitated silica is filtered and washed with water to remove the soluble salts. The third step of the process involves purification of wet impure silica which has obtained above. For this successive demineralized water washings were given for the removal of sulphate impurities constitute and then dried to obtain the amorphous powder form [25, 26]. Precipitation of silica from RHA involves the following reactions SiO 2 + 2NaOH C Na2SiO 3 + H2O Ash Caustic soda DIGESTION Sodium silicate Water Na 2 SiO 3 + H 2 SO C SiO 2 + Na 2 SO 4 + H 2 O Sodium silicate Sulphuric acid PRECIPITATION Silica Sodium sulphate Water Formulation of emulgel Different formulations were prepared using varying amounts of gelling agent. The method only differed in the process of making gel in different formulations. The preparation of emulsion was same in all the formulations. The gel bases were prepared ~ 26~

4 by dispersing Carbopol 934 and Carbopol 940 in distilled water separately with constant stirring at a moderate speed using mechanical shaker. Formulations F1, F2 and F3 were prepared by Carbopol 934 and F4, F5 and F6 by Carbopol 940 as gelling agent. In formulations F7, F8 and F9 the gels were prepared by dispersing HPMC K100 in heated distilled water at 80 C, then the dispersion was cooled and left overnight for the hydration of gel. The ph of all the formulations was adjusted to using triethanolamine (TEA). The oil phase of the emulsion was prepared by dissolving Span 20 in coconut oil. Silica being hydrophobic was also dissolved in oil phase while the aqueous phase was prepared by dissolving Tween 20 in purified water. Methyl and Propyl parabens were dissolved in propylene glycol and mixed with the aqueous phase. Both the oily and aqueous phases were separately heated to C, then the oily phase was added to the aqueous phase with continuous stirring until it got cooled down to room temperature. The obtained emulsion was mixed with the gel in 1:1 ratio with gentle stirring to obtain the emulgel. Table 1. Composition of emulgel formulations Ingredients (% w/w) F1 F2 F3 F4 F5 F6 F7 F8 F9 Aloe Vera Gel (ml) Precipitated Silica (%) Carbopol 934 (%) Carbopol 940 (%) HPMC K100 (%) Tween 20 (ml) Span 20 (ml) Coconut Oil (ml) Propylene Glycol (ml) Methyl Paraben (g) Propyl Paraben (g) Characterization of emulgel formulations Preformulation studies were carried out which involves IR spectral analysis to check the compatibility among drug, silica and polymers used in formulating emulgel. The prepared emulgel formulations were inspected visually for their color, homogeneity, consistency, grittiness and phase separation. The ph of emulgel formulations was determined by using digital ph meter. All measurements for each formulation were done in triplicate and average mean values were thereby calculated. Viscosity of the prepared emulgels was determined using Brookfield viscometer [Spindle type, model LVDV-1(prime)] at 10 rpm [27]. Spreadability denotes the extent of area to which the emulgel readily spreads on application to skin. The bioavailability or efficiency of a formulation also depends on its spreading value. The hair care emulgel formulation was sandwiched between two slides in an area occupied by a distance of 7.5 cm along the slide. The time taken for the upper slide to travel the distance of 7.5 cm and separated away from the lower slide under the influence of the weight was noted. Spreadability was calculated by using the following formula, S = m x l/t where, S-spreadability, m-weight tied to the upper slide (20gm), l-length of the glass (7.5 cm) and t-time taken in seconds. The extrudability test was carried out by using Pfizer hardness tester. About 15 g of emulgel was filled in an aluminium tube and the plunger was adjusted to hold the tube properly. The pressure of 1kg/cm 2 was applied for 30 sec and the quantity of gel extruded was weighed by repeating the same at three equidistance places of the tube [28]. The primary skin irritation test was performed on male albino rats to check whether product is safe to be used on skin. All the experimental protocols were approved by the Institutional Animal Ethical Committee of Al Shifa College of Pharmacy, Perinthalmanna, Kerala (approval reference number: IAEC.025/16). Test animals were maintained on standard animal feed and free access to water. They were kept under standard laboratory conditions. Dorsal abdominal hairs were shaved carefully and 50 mg of prepared emulgel was applied to the skin of wistar albino rats. After 24 hours of exposure, the applied emulgel was removed, ~ 27~

5 washed with tap water and checked for undesirable skin changes i.e. change in skin colour or morphology. RESULTS According to the IR spectrums as shown in Figure 1, the principal absorption frequencies of silica (1126, 809, 452 and 200 cm -1 ) were also observed in spectrums of silica with polymers which indicates that there was no incompatibility between silica and different polymers used in formulating emulgel [29]. The prepared emulgel formulations were white colored viscous creamy preparations with a smooth and homogeneous appearance. They were easily spreadable with acceptable bioadhesion and fair mechanical properties. All formulations showed good homogeneity with absence of lumps and greasiness. The ph values of all the prepared formulations were measured using digital ph meter and ranged from 5.4 to 5.8, which is considered acceptable to avoid the risk of irritation upon application to hair and scalp. The rheological behavior of all formulated emulgels was studied using viscometer with spindle 64 at 10 rpm. In gel system, consistency depends on the ratio of solid fraction, which produces the structure to liquid fraction. Viscosity of various formulated emulgels was found in range of centipoises which in turn implies that it depends upon the polymer concentration. A B C ~ 28~

6 Figure 1. IR Spectrum of A) Silica, B) Silica+Carbopol 934, C) Silica+Carbopol 940 & D) Silica+HPMC K100 D The value of spreadability indicates that the emulgel is easily spreadable by small amount of shear. Spreadability of HPMC and Carbopol 940 gel was in the range gcm/sec whereas for Carbopol 934 it was in the range gcm/ sec which indicate spreadability of Carbopol 934 containing emulgel was good as compared to HPMC and Carbopol 940 emulgel. The extrusion of the emulgel from the tube is very important during its application and in customers acceptance. Emulgels with high consistency may not extrude from tube whereas, low viscous gels may flow quickly, and hence suitable consistency is required in order to extrude the emulgel from the tube. Extrudability of the prepared emulgel formulations was found to be acceptable. Mean globule size in emulgel was found to be 2417 nm. The poly dispersity index (PDI) of the prepared emulgel was found to be which proves the homogeneity of emulgel. The optimized formulation was checked on healthy Albino rats for skin irritation which had shown no erythema, edema or reddening of skin. This observation indicates acceptability of this emulgel for topical use. Table 2. Characterization of emulgel formulations Formulation Code Homogeneity* Consistency* Exdrudability* ph Viscosity (centipoise) Spreadability (gcm/sec) F F F F F F F F F *+++ Good, ++Satisfactory, +Fair The skin irritation studies revealed that the formulation F2 was non-sensitizing and safe for use which also underwent stability studies as per ICH guidelines at 40±2 0 C and 75±5% RH for 6 months. The results revealed that no significant changes in the physicochemical and rheological behaviors of the selected emulgel. DISCUSSION AND CONCLUSION The aim of the study, to formulate and evaluate a hair care emulgel from rice husk ash was successfully attained through this proposed research work. The silica was extracted from RHA using caustic soda and dilutesulphuric acid. The extracted silica was formulated into six different formulations by changing the concentrations of Carbopol 934, Carbopol 940 and HPMC K100. On evaluation of all the formulations, F2 (1.5 % Carbopol 934) was found to be optimum in terms of gel consistency, viscosity, spreadability and significant difference in the physical and chemical parameters. Pharmacological evaluation of emulgel revealed that all formulations ~ 29~

7 are non-irritating and safe for use. Emulgel, a type of topical preparation is very pleasant to use and also easily washed with water. In this aspect it was found to be far superior to other formulations, thus fulfilling the objectives of the study. The coming years will witness an excessive use of hair care products as these ensure better compliance and constitute an effective hair care option, devoid of side effects. More clinical and human studies have to be performed to evaluate the effectiveness of product in the management of hair. REFERENCES [1]. Robertson MI. Regulatory issues with excipients. Int J Pharm. 187, 1999, [2]. Rowe R, Sheskey P, Quinn M. Handbook of Pharmaceutical Excipients, APhA, 6, [3]. Yoshioka S, Stella V. Stability of Drugs and Dosage Forms. Kluwer Academia Publishers [4]. Florke, Otto W. "Silica" in Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. 2008; doi: / a23_583.pub3 [5]. Baibhav, Rana AC, Seema S, Vikas S. Emulgel: a comprehensive review on the recent advances in topical drug delivery. Int Res J Pharmacy. 2(11), 2011, [6]. Stan-Posthumd JJ, Vink J, Lecessies, Bruijn JA. Topical tretinoin under oocclusion on a typical navei. Asn J Pharm Clnl Res. 3, 1988, 548. [7]. YogeshPounikar, Pushpendra Jain, NavneetKhurana, Omray K, Patil S. Formulation and characterization of aloe vera cosmetic herbal hydrogel. Int J Pharm Pharm Sci. 4(4), 2012, [8]. Eshu K, He Q. Aloe vera: a valuable ingredient for the food, pharmaceutical and cosmetic industries--a review. Critical reviews in food sci and nutrition. 44, 2004, [9]. Grace OM, Simmonds MS, Smith GF, Wyk AE. Therapeutic uses of Aloe L. (Asphodelaceae) in southern Africa. J Ethnopharmacol. 119, 2008, [10]. Abdul Wadood Khan, SabnaKotta, ShahidHussain Ansari, Rakesh Kumar Sharma, Amit Kumar, Javed Ali. Formulation development, optimization and evaluation of aloe vera gel for wound healing. Pharmacogn Mag. 9(1), 2013, S6 S10. [11]. Khullar R, Saini S, Sethi N, Rana AC. Emulgel A surrogate approach for topically used hydrophobic drugs. Int J Pharm Biol Sci. 4(1), 2011, [12]. Mohamed MI. Topical emulsion gel composition comprising diclofenac sodium. AAPS J. 6(3), 2004, 26. [13]. Botchkareva NV, Ahluwalia G, Shander D. Apoptosis in the hair follicle. J Invest Dermatol. 126, 2006, [14]. Stenn KS, Paus R. Controls of hair follicle cycling. Physiol Rev. 81, 2001, [15]. Fernandez Ledesma E, Rodriguez Acosta C, LivaGarrido M, DiazPolanco I, CazanaveGuarnaluce D. Evaluation of rice husk as an excipient for the pharmaceutical industry. J Mater Environ Sci. 6(1), 2015, [16]. Rieger MM, Lachman L, Lieberman HA, Kaing JL. The theory and practice of industrial pharmacy. PA Lea and Febiger, Philadelphia. 3, 1986, [17]. Beth Johnson, Lylenette Canfield. New Approaches for Assessing Conditioning and Quantifying Silicone Deposition on Hair. Dow Corning. 27(1247A-01), 2012, 1-5. [18]. Vasanthi N, Lilly, Saleena M. Silicon in Day Today Life. World ApplSci Journal. 17(11), 2012, [19]. Herrwerth S, Ulrich-Brehm I, Kortemeier U, Winter P. Silicone Quaternium-22: New Silicone Technology for Premium Hair Conditioning with Additional Benefits. SOFW-Journal. 6, 2009, 1-7. [20]. Subbukrishna DN, Suresh KC, Paul PJ. Precipitated silica from rice husk ash by IPSIT process. European biomass conference and exhibition. 15, 2007, [21]. Muxin Liu, AmroRagheb, Paul Zelisko. Preparation and Applications of Silicone Emulsions Using Biopolymers. Elaissari. 4304(Ch26), 2003, [22]. Adriana Urrutia. Silicone: The Basis of a Perfect Formulation for Hair Care. Dow Corning; 25, 2001, [23]. Kalapathy U, Proctora A, Shultz J. A simple method for production of pure silica from rice hull ash. Bioresource Technology. 73, 2000, [24]. Garaud JL: Silicones in Personal Care Applications, Dow Corning, Europe, SA, 1998, ~ 30~

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