Formulation and Evaluation of SR Tablets of Anti-diabetic drug Gliclazide

Abstract

Recent advances in Sustained Release Drug delivery System (SRDDS) aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance. This present study showed that the Gliclazide is an oral hypoglycemic (anti-diabetic drug) and is classified as a sulfonylurea. Its classification has been ambiguous, as literature used it as both a first generation and second generation sulfonylurea. Gliclazide was shown to protect human pancreatic beta-cells from hypoglycemia-induced apoptosis. It was shown to have an anti-atherogenic effect (preventing accumulation of fat in arteries) in type II diabetes. Gliclazide is used in the tablet form for antidiabetic effect. Keyword: Gliclazide, Sustained release tablet, Pharmacokinetic study, diabetes, GLI, glipizide. *Corresponding Author Email: [email protected] Received 04 April 2019, Accepted 18 April 2019 Journal home page: http://www.ajptr.com/ Tiwari., Am. J. PharmTech Res. 2019;9(03) ISSN: 2249-3387 www.ajptr.com 2 INTRODUCTION The oral route of administration is the most preferred route because of its numerous advantages. Tablets and capsules are the most preferred dosage form of pharmaceutical scientists and clinicians because of its convenience in the term of selfadministration, compactness, ease in manufacturing, high precision dosing, and relatively low cost production. Gliclazide is structurally classified as a sulphonyl urea second generation analogue. The mean absolute bioavailability of Gliclazide sustained release was 97%. It shows the linear pharmacokinetic . The objective of present work was to prepare sustained release tablet of GL by wet granulation method and study to effect on IR MATERIALS AND METHOD Materials Gliclazide was received as gift sample from Micro Labs Hosur. All other chemicals used in this experiment were of analytical grade obtained commercially. Tablet is prepared by following these methodsWet Granulation The most widely used process of agglomeration in pharmaceutical industry is wet granulation. Wet granulation process simply involves wet massing of the powder blend with a granulating liquid, wet sizing and drying. Important steps involved in the wet granulation \uf0b7 Mixing of drug and excipients. \uf0b7 Preparation of Binder solution. \uf0b7 Mixing of binder solution with powder mixture to form wet mass. \uf0b7 Drying of moist granules. \uf0b7 Mixing of screened granules with disintegrant, glidant and lubricant. Advantages 1. Permits mechanical handling of powders without loss of mix quality. 2. Improves the flow of powders by increasing particle size and sphericity Dry Granulation In dry granulation process the powder mixture is compressed without the use of heat and solvent. It is the least desirable of all methods of granulation. The two basic procedures are to form a compact of material by compression and then to mill the compact to obtain a granules. Two methods are used for dry granulation. The more widely used method is slugging, where the powder is Tiwari., Am. J. PharmTech Res. 2019; 9(03) ISSN: 2249-3387 3 www.ajptr.com recompressed and the resulting tablet or slug are milled to yield the granules. The other method is to recompress the powder with pressure rolls using a machine such as Chilosonator. Roller Compaction The compaction of powder by means of pressure roll can also be accomplished by a machine called chilsonator. Unlike tablet machine, the chilsonator turns out a compacted mass in a steady continuous flow. The powder is fed down between the rollers from the hopper which contains a spiral auger to feed the powder into the compaction zone. Like slugs, the aggregates are screened Use. Use in the production of directly compressible excipients, the compaction of drugs and drug formulations, the granulation of inorganic materials, the granulation of dry herbal material and the production of immediate/sustained release formulations. Direct compression. Gliclazide tablet is prepared by wet granulation methodThe granules were prepared by wet granulation method. Gliclazide and MCC were passed through #40 mesh. The binder solution was prepared by dissolving the povidone in purified water. The sifted blend was mixed in rapid mixer granulator at 150 rpm for 15mints in slow speed. The binder solution was added to the blend and allowed to mix thoroughly until to get granules. The obtained granules was dried in fluidized bed drier at 60°C for 60mints until to get LOD of granules not less than 2%w/w. The dried granules were sifted through #20 mesh. HPMC-K100LV, Lactose DCL-15 and iron oxide red were sifted through sieve no#40 and 100 mesh and mixed with dried granules for 10 minutes in RMG. The granules thus obtained was mixed with magnesium stearate (which was sifted through sieve no#60) for 2mints. Final blend was collected and compressed. Table 1: Formulation of Gliclazide tablet Sr. no. Ingredients Formulation code(mg) F1 F2 F3 F4 F5 1. Gliclazide 30 30 30 30 30 2. HPMC K4M 5 8 7 6 7 3. HPMC K100M 8 10 5 8 7 4. Ethyl cellulose 5 2 3 3 2 5. NaHCo3 5 2 5 5 5 6. Talk 2 1 3 4 3 7. Mg. stearate 2 5 5 2 4 8. Lactose Qs QS QS QS QS Tiwari., Am. J. PharmTech Res. 2019;9(03) ISSN: 2249-3387 www.ajptr.com 4 Evaluation of Tablets Blend Precompression The quality of tablet, once formulated, is generally dictated by the quality of physicochemical properties of blend. There are many formulation and process variables involved in mixing step and all these can affect the characteristics of blends produced. Angle of Repose (θ) The frictional forces in a loose powder can be measured by the angle of repose (θ). It is an indicative of the flow properties of the powder. It is defined as the maximum angle possible between the surface of a pile of powder and the horizontal plane. Angle of repose was determined by using funnel method. Powder was poured from funnel, which can be raised vertically until a maximum cone height. (Chaulang et al., 2008 &Lakshmi et al., 2011) θ = tan h r Whereas; θ is angle of repose h is height of pile and r is the radius of the base pile. Standard range for measurement of angle of repose Angle of repose (\uf071) Type of flow \uf03c 25 Excellent 25-30 Good 30-40 Passable (addition of 0.2% Glidant is required) \uf03e 40 Poor Bulk Density (Db) It is the ratio of total mass of powder to the bulk volume of powder. It was measured by pouring the weighed powder (passed through standard sieve #20) into a measuring cylinder and the initial volume was noted. From this, the bulk density is calculated according to the formula mentioned below. It is expressed in g/ml and is given by (Lakshmi et al., 2011) Db = M Vb Where, M is the mass of powder Vb is the bulk volume of the powder. Tapped Density (Dt). It is the ratio of total mass of powder to the tapped volume of powder. The volume was measured by tapping the powder for 100 times. Tapping was continued until the difference between Tiwari., Am. J. PharmTech Res. 2019; 9(03) ISSN: 2249-3387 5 www.ajptr.com successive volumes is less than 2% (in a bulk density apparatus). It is expressed in g/ml and is given by (Lakshmi et al., 2011) Dt = M Vt Where, M is the mass of powder Vt is the tapped volume of the powder. Compressibility Index (Carr’s Consolidation Index) One of the ways of measurement of free flowing powder is compressibility as computed from density of a powder. It was calculated by using the formula. (Lakshmi et al., 2011) % Compressibility = ( Tapped Density − Bulk Density Tapped Density ) × 100 Standard values for Carr’s index (\uf025 compressibility) Carr’s index Type of flow 5-15 Excellent (free flowing granules) 12-16 Good (free flowing powdered granules) 18-21 Fair (powdered granules) 23-35 Poor (fluid cohesive powder) 33-38 Very poor (fluid cohesive powder) \uf03e 40 Extremely poor (cohesive powder) Hausner Ratio Hausner ratio is an indirect index of ease of powder flow. If the Hausner ratio of powder is near to 1.25, indicates better powder flow. It is calculated by the formula(Lakshmi et al 2011) Hausner Ratio = Dt Db Where, Db = Bulk density of the powder Dt = Tapped density of the powder. EVALUATION OF SR TABLETS: Post compression parameters: Appearance: Uncoated tablets were examined under a lens for the shape of the tablet and colour was observed by keeping the tablets in light. Dimension: Thickness and diameter were measured using a calibrated barmier calliper. Six tablets of each formulation were picked randomly and dimensions determined. and it was determined to within +_ 0.01mm. Tiwari., Am. J. PharmTech Res. 2019;9(03) ISSN: 2249-3387 www.ajptr.com 6 Weight Variation Test Twenty tablets were weighed individually and all together. Average weight was calculated from the total weight of all tablets. The individual weights were compared with the average weight. The percentage difference in the weight variation should be within the permissible limits (±7.5%). The percent deviation was calculated using the following formula.(Kuchekar et al., 2004). Percentage Diviation = ( Individual weight − Average weight Average weight ) × 100 The weight was determined by using Sartorius balance and there is shown that every individual in a batch should be in uniform weight and weight variation within the permissible limits. IP Standards for Percentage Weight Variation Average weight. Percentage deviation 80 mg or less. 10 More than 80 mg but less then 250 mg 7.5 250 mg or more 5 Hardness test: Hardness indicates the ability of a tablet to withstand mechanical shocks while handling. The hardness of the tablets was determined using Monsanto hardness tester. It is expressed in kg/cm. Six tablets were randomly picked and analyzed for hardness. The mean and standard deviation values were also calculated. (Lachman et al., 1991) A tablet hardness about is 6-8kg was considered adequate for mechanical stability. Friability test Friability is the loss of weight of tablet in the container/package, due to removal of fine particles from the surface. This