Journal home page: EVALUATION OF BINDING EFFICACY OF MUCILAGE OF CISSUS QUADRANGULARIS IN TABLET DOSAGE FORM

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1 Page5281 Indo American Journal of Pharmaceutical Research, 2013 ISSN NO: Journal home page: INDO AMERICAN JOURNAL OF PHARMACEUTICAL RESEARCH EVALUATION OF BINDING EFFICACY OF MUCILAGE OF CISSUS QUADRANGULARIS IN TABLET DOSAGE FORM V. Hema Faith*, Subhashis Debnath, M. Niranjan Babu Department of Pharmaceutics, Seven Hills College of Pharmacy, Tirupathi , Andhra Pradesh, India. ARTICLE INFO Article history Received 03/07/2013 Available online 30/07/2013 Keywords Cissus Quadrangularis Mucilage, Binding Agent, Paracetamol, Dissolution. ABSTRACT The objective of the present research was to evaluate the mucilage of Cissus quadrangularis as a tablet binder employing paracetamol as a model drug. The mucilage was isolated from stems of Cissus quadrangularis. Physicochemical characteristics of mucilage were studied. Different formulations of tablets using Cissus quadrangularis mucilage were prepared by wet granulation method. The binder concentrations in the present tablet were1%, 2%, 4%, 6%, 8%, and 10%. Tablets were prepared and subjected for evaluation of hardness, friability, drug content uniformity. Preliminary evaluation of granules showed that to 28.51º angle of repose and to compressibility index %. Tablet hardness was found to be in the range of 4.01 to 6.7 kg/cm2, 0.42 to 4.21 min disintegration time and more than 90.00% dissolution in 120 min. Tablets at 6% w/v binder concentration showed optimum results as tablet binder. The Cissus quadrangularis mucilage was found to be useful for the preparation of tablet dosage form. Corresponding author V. Hema Faith Department of Pharmaceutics, Seven Hills College of Pharmacy, Tirupathi , Andhra Pradesh, India. nissy.noya@gmail.com. Please cite this article in press as V. Hema Faith et.al. Evaluation of binding efficacy of mucilage of cissus quadrangularis in tablet dosage form. Indo American Journal of Pharm Research.2013:3(7). Copy right 2013 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 Page5282 INTRODUCTION: Binders are added to tablet formulation to impart plasticity and thus increase the interparticulate bonding strength within the tablet. The development of new excipients for potential use as binding agent in tablet formulations continues to be of interest. This is because different binding agents can be useful in achieving various tablet mechanical strength and drug release properties for different pharmaceutical purpose. Binders are agents employed to impart cohesiveness to the granules. This ensures the tablet remains intact after compression as well as improving the flow qualities by the formulation of granules of derived hardness and size. To hold various powders together to form a tablet is a binder, fillers usually do not have good binding capacity, binder is either added in dry mix or mix in granulating liquid, binder form matrix with fillers and drug embedded in it, on drying solid binder forms glue which holds the particles together, the wet binder is the most important ingredient in the wet granulation process, most binders are hydrophilic & most times soluble in water. A large number of plant based pharmaceutical excipients are available today. Gums and mucilages are the most commonly available plant ingredients with a wide range of applications in pharmaceutical and cosmetic industries. In recent years, plant derived polymers have evoked tremendous interest due to their diverse pharmaceutical applications such as diluents, binders, disintegrants in tablets, thickeners in oral liquids, protective colloids in suspensions, gelling agents in gels and bases in suppository. The plant based polymers have been studied for their application in different pharmaceutical dosage forms like matrix controlled system, film coating agents, buccal films, microspheres, nanoparticles, viscous liquid formulations like ophthalmic solutions, suspensions, implants and their applicability and efficacy has been proven. These have also been utilized as viscosity enhancers, stabilizers, disintegrants, solubilizers, emulsifiers, suspending agents, gelling agents and bioadhesives. Different starches like rice, potato, maize, corn, wheat, tapioca starch and gums like ferula gummosa boiss, gum olibanum, beilschmiedia seed gum, okro gum, aegle marmelod gum, gum cordial, okra gum and cassia roxburghii seeds gum and plant fruit like date palm fruit and orange peel pectin shows good potency as a binding agent. 1 Cissus quadrangularis is an annual or perennial herb with huge medicinal properties distributed throughout the tropical world. It is found throughout the hotter parts of India, Malasiya, Singapore Pakistan, Bangladesh, Thailand, Java, Philippines,West Africa and Ceylon. 2 The fresh stems of Cissus quadrangularis plant has been used medicinally in treatment of gastritis, bone fractures, skin infections, constipation, eye diseases, piles, anaemia, asthma, irregular menstruation, burns and wounds. Fresh levaes and roots are used as antimicrobial, dry stem extracts shows antioxidant activity. Also used in treatment of cardiovascular diseases, diabetes, epilepsy. The various phytochemical constituents present in cissus stems are carbohydrates, gums and mucilages, proteins, aminoacids, alkaloids, glycosides, phytosterol, flavanoids, tannins and phenolic compounds. 3 The present work is an attempt to extract and investigate the pharmaceutical properties of the mucilage to assess its suitability as a binding agent in the pharmaceutical formulation. Binding ability was used as the basis for evaluating the performance of Cissus quadrangularis mucilage as binding agent. MATERIALS AND METHODS: Paracetamol (SDFCL-SD Fine Chemicals Ltd, Mumbai), Acacia (Loba Chemie pvt Ltd, Mumbai), Starch (Final chemicals Ltd, ahmedabad), Lactose (Oxford Laboratory, Mumbai), Magnesium stearate (Himedia Laboratories Pvt Ltd, Mumbai), Talc (Accord Labs, Hyderabad) was procured from open market. All the other solvents, reagents used were of pharmacopoeial and analytical grade. Cissus quadrangularis stems were collected form sorroundings of venkatramapuram, Tirupathi. Matured stems were selected because they contain more mucilage content when compared to tender stems.

3 Page5283 Method for Extraction of mucilage: The stems of cissus plant were thoroughly washed to remove sandy matter. Stems are chopped and made into smooth paste, which is heated by adding small amount of water for 1 hr till it turns to pale green in colour. And the extract was squeezed through musclin cloth which is collected and poured into tray dryer and heated upto 80 c. Then the dried extract was scrapped and pulverised and sieved through 100# mesh to get powdered extract which is stored in an air tight containers. Mucilage is extracted by adding powdered extract to separating funnel which is filled with equal amounts of chloroform and water and shaked for 15 minutes and kept aside for 24 hrs. Then the aqueous extract was carefully collected and heated to get powdered mucilage, which is stored in a dessicator. 4 The physicochemical properties of extracted mucilage mentioned in Table No:2. Drug-excipient compatability studies: This study has been done to check whether there is any compatibility related problems are associated with drug and excipients used for the formulation of tablet. The drug and excipients must be compatible with one another to produce a product that is stable, efficacious, attractive and easy to administer and safe. If the excipients are new and not been used in formulations containing the active substance, the compatibility studies are of paramount importance. FTIR can be used to investigate and predict any physicochemical interactions between components in a formulation and can therefore be applied to the selection of suitable chemically compatible excipients. FTIR Spectroscopy: The IR spectral analysis of a drug and other excipients were taken using Press pellet technique (using KBr). The IR spectra s were determined by using IR spectrometer (BRUKER) wavelength from 4000 cm -1 to 400 cm -1 shown in Fig No: 1, 2. Phytochemical examination: Preliminary tests were performed to confirm the nature of mucilage obtained. The chemical tests that were conducted are: Ruthenium red test, Molisch test. Preparation and evaluation of granules: Paracetamol was used as a model drug to formulate granules. Starch was used a disintegrant, whereas lactose and magnesium stearate were used as diluents and lubricant respectively as in working formula (Table 1). The binder solution was prepared by dissolving the mucilage of cissus quadrangularis in water at 1%, 2%, 4%, 6%, 8%,10% w/v concentrations. The granules were prepared by wet granulation process. The drug, lactose and starch were mixed thoroughly and a sufficient volume of different concentrations of binding agent cissus mucilage was added slowly to powder blend, and kneading was performed for some time until formation of wet mass with enough cohesiveness. The wet mass is forced through a no. 10 sieve. The same process was used for preparation of standard granules using acacia as a binder and a combination of acacia+mucilage (50:50) was also formulated.

4 Page5284 Table 1: Formulation design of paracetamol tablets with different binder concentrations of Cissus mucilage INGREDIENTS M 1 M 2 M 3 M 4 M 5 M 6 A 1 A 2 A 3 A 4 A 5 A 6 A 7 (650 MG) Paracetamol(mg) Cissus mucilage (mg) Lactose (mg) starch (mg) Talc (mg) Magnesium stearate (mg) Acacia (mg) (M)+ 32.5(A) Preparation and evaluation of tablets: The tablets were compressed by using 16 station rotary tablet machine (Cadmach Machinery, Ahmedabad) using 12 mm flat-faced punches. The batch size of 100 tablets was prepared. The prepared tablets were evaluated for content uniformity, hardness, friability, disintegration time and invitro dissolution profile. 7 (Table 4). In-vitro dissolution procedure: In dissolution test the release rate of paracetamol from tablets was determined using USP dissolution test apparatus (paddle: type II) (Labindia). The dissolution test was performed using 900 ml phosphate buffer (ph 7.2), at 37 c with speed of 50 rpm and the samples are withdrawn at time intervals 5, 10, 15, 20, 25, 30, 40, 50, 60, 80, 90,120 mints and The samples were suitably diluted with the dissolution fluid and assayed for paracetamol at 257nm and using the corresponding dissolution fluid as blank. And the cumulative amount of drug release is calculated using standard calibration curve. Each sample withdrawn was replaced with an equal amount of drug free dissolution fluid. And the cumulative amount of drug release from the formulations with different concentrations of binder(cissus mucilage) and standard binder (acacia) are mentioned below in Table:5,6. And graphical representation of drug release profile shown in Fig: 3,4. RESULTS AND DISCUSSION The dried mucilage was isolated using water as a mucilage precipitating solvent. The physicochemical properties of mucilage was determined and shown in Table No:2. The ph of the mucilage is near to neutral, so it may be less irritating to gastro-intestinal tract.

5 Page5285 Table 2: Physicochemical characteristics of mucilage. S. No Parameters Results 1. Solubility Insoluble in acetone, ethanol, chloroform. Soluble in water. 2. P H Loss on drying 12.01% 4. Bulk density Compressibility index Tapped density Hausner s ratio Angle of repose ǀ The drug-excipient compatability studies showed after interpretation through the below spectra in Fig no 1,2 it was confirmed that there are no major shifting as well as no loss of functional peaks between the spectra of mucilage, physical mixture of drug and mucilage. From the I.R studies it was concluded that, the selected binding agent and other excipients are compatible with the selected Drug paracetamol. Figure 1: IR spectrum of mucilage Figure 2: IR spectrum of drug+ mucilage The prepared granules are evaluated for flow properties (Table No:3). It was observed that friability was reduced as the concentration of gum was increased. The flow property of granules was determined by angle of repose, which was found to be to Hence all the granules exhibited good flow properties.

6 Page5286 Formulation code Table 3: Precompression parameters paracetamol and acacia granules Bulk density (g/ml)±sd* Tapped density (g/ml) ±SD* Parameters Compressibility index (%)±SD* Hausner s ratio ±SD* Angle of repose (degrees) ±SD* M ± ± ± ± ±0.04 M ± ± ± ± ±0.02 M ± ± ± ± ±0.05 M ± ± ± ± ±0.06 M ± ± ± ± ±0.03 M ± ± ± ± ±0.04 A ± ± ± ± ±0.01 A ± ± ± ± ±0.02 A ± ± ± ± ±0.03 A ± ± ± ± ±0.02 A ± ± ± ± ±0.02 A ± ± ± ± ±0.02 A ± ± ± ± ±0.03 Values are means of SD± n=3. The bulk densities of prepared granules were found to decrease slightly by increasing concentrations of cissus quadragularis mucilage. This result may be due to formation of larger agglomerates and the decrease in fines in the granules as increasing cissus quadragularis mucilage provides more binding to the granules. The compressibility index indicates a decrease in flowability with increasing cissus quadragularis mucilage. All the formulations showed good flow properties. In general, compressibility index upto 20% showed excellent flow properties. Six batches of 100 tablets were prepared using gum of cissus quadragularis mucilage at six different concentrations viz 1%, 2%, 4%, 6%, 8% and 10% w/v. Acacia was used as binder for comparison. The prepared tablets were evaluated for content uniformity, hardness, friability, disintegration time and in vitro dissolution profiles. All the batches of tablets exhibited good uniformity of content (Table No:4). Table 4: Post compression parameters of mucilage and acacia tablets. Formulation codes Weight variation (mg) ± SD Hardness (kg/cm 2 ) ± SD Parameters Friability (% weight loss) ± SD Disintegration time (min)±sd Drug content (mg/tab) ± SD M ± ± ± ± ±0.125 M ± ± ± ± ±0.13 M ± ± ± ± ±1.3 M ± ± ± ± ±0.19 M ± ± ± ± ±0.23 M ± ± ± ± ±0.42 A ± ± ± ± ±0.30 A ± ± ± ± ±0.27 A ± ± ± ± ±0.06 A ± ± ± ± ±0.01 A ± ± ± ± ±0.22 A ± ± ± ± ±0.16 A ± ± ± ± ±0.17 Values are means of SD± n=3.

7 Page5287 The hardness of tablets increased with increase in percentage of binding agent as well in combination of acacia+mucilage. It is well known that a high concentration of a plasto-elastic binding agent leads to an increase in plastic deformation of the formulation and subsequently to the formation of more solid bonds, resulting in tablets with more resistance to fracture and abrasion. The tablets (6%) of cissus quadragularis mucilage showed good hardness when compared to tablets (8%) Acacia. Table 5: Invitro drug release data of paraceetamol tablet formulations containing mucilage in different binder concentration. Time (mints) Cumulative % of drug release Formulation codes M 1 M 2 M 3 M 4 M 5 M ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.08 Values are means of SD± n=3. The percentage friability values were reduced as the concentration of gum was increased. Conventional compressed tablet lose their weight less than 0.5 to 1.0% are generally considered as acceptable. The mucilage with increase in concentration, increase in disintegration time. The disintegration time of tablet (6% mucilage) was in limits when compared to 8% acacia (Table No:4). The in vitro dissolution profile is shown in (Figure No:3,4). It was found that the drug release decreased with increase in concentration of mucilage. All the batches showed the good drug release (Table No:5,6). This study showed that the drug release from the tablets prepared using gum at six different concentrations was more than 90.00% at the end of 120 min. These tablets had given reduced diffusion of drug.

8 Page5288 Table 6: Invitro drug release data of paracetamol tablet formulations containing acacia at different binder concentration Time (mints) Cumulative % of drug release Formulation codes A 1 A 2 A 3 A 4 A 5 A 6 A ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.12 Values are means of SD± n=3. Figure 3: Drug release profile of mucilage formulations with different binder concentrations. (M1,M2,M3,M4,M5,M6- with different binder concentrations of (mucilage) 1%,2%,4%,6%,8%,10%) Figure 4: Drug release profile of acacia formulations with different binder concentrations. (A1,A2,13,A4,A5,A6,A7- with different concentrations of binder (acacia) 1%,2%,4%,6%,8%,10%)

9 Page5289 CONCLUSION From the present study, it can be concluded that cissus quadragularis mucilage at 6% w/v exhibited good binding properties comparable to that of 8% acacia. Mucilage can be used as a binding agent for the preparation of tablets. The increased concentration of gum showed slight retardation in drug release. Hence, there is further need to study the cissus quadragularis mucilage for sustained release dosage forms. REFERENCES 1. Vipul D. Prajapati, Girish K. Jani, Naresh G. Moradiya, Narayan P. Randeria (2013). Pharmaceutical applications of various natural gums. Mucilages and their modified forms. Carbohydrate polymers 92 : Anitha R, Suji P (2012). Pharmacognostic evaluation of Cissus quadrangularis L.Stem. International journal of pharmaceutical sciences and research 3 (7): Garima Mishra, Saurabh Srivastava B, Nagori P (2010). Pharmacological and therapuetical activity of Cissus quadrangularis: An overview. International journal of pharmtech research 2 (2) : Owuno F, Eke-Ejiofor J, Wordu G (2012). Effects of cissus (Cissus populnea) gum on dough rheology and quality of wheat cassava composite bread. Journal of food, agriculture & environment 10 (2) : Enauyatifard R, Azadbakht M, Fadakar Y (2012). Assesment of Ferula gummosa gum as a binding agent in tablet formulations. Acta poloniac pharma. Drug research 69: Oyi AR, Olayemi OJ, Allagh TS (2009). Comparative binding effects of wheat, rice and maize starches in chloroquine phosphate tablet formulations, Res. J. App. Sci. Eng. Tech. 1: Gilbert S. Banker, Neil R. Anderson (2009). Tablets. In The Theory and Practice of Industrial Pharmacy (Lachman L, Lieberman HA), Special Indian edition, CBS publishers. pp