The Pharma Innovation Journal 2018; 7(10): 447-455
ISSN (E): 2277- 7695 ISSN (P): 2349-8242 NAAS Rating: 5.03 Comparitive in-vitro drug release study of enteric TPI 2018; 7(10): 447-455 © 2018 TPI coated rabeprazole tablets using synthetic and www.thepharmajournal.com Received: 21-08-2018 natural polymers Accepted: 24-09-2018
Sofia Konain Sofia Konain and Sirisha Mittapally Deccan School of Pharmacy, Dar-us-salam, Aghapura, Nampally, Hyderabad, Abstract Telangana, India Enteric coated tablets are tablets which are coated with polymers to prevent the release of drug in the stomach and allow the drug release in the small intestine. Enteric Coating is used to protect the active Sirisha Mittapally Pharmaceutical Ingredient from the acidic environment and to prevent gastric distress caused from a drug Deccan School of Pharmacy, due to irritation. The purpose of this research work is formulation of enteric coated tablets using Dar-us-salam, Aghapura, Synthetic and Natural polymers and comparing their release studies. Nine formulations of Rabeprazole Nampally, Hyderabad, core tablets were formulated from which F9 was found to be the optimized one. Then the optimized core Telangana, India tablet was coated with 4 different polymers- Eudragit L100, HPMC, Sodium Alginate and Shellac with different concentrations F1 to F16. Compatibility studies were performed which showed no interaction.
The dissolution study shows that Eudragit L100 has 100% drug release and the natural polymers Sodium
Alginate and Shellac were also equally effective. Therefore, it can be concluded based on the experimental studies that the natural polymers can also be a good alternative to synthetic polymers. Out of the two Natural Polymers, Shellac exhibited good performance compared to Sodium Alginate.
Keywords: enteric coating, rabeprazole, synthetic polymers, natural polymers, eudragit l100, sodium alginate, shellac, HPMC, anti-ulcer drug
Introduction
Solid dosage form A solid dosage form is drug delivery system that includes tablets, capsules, sachets and pills as well as a bulk or unit-dose powders and granules. Oral route of drug administration is widely acceptable, and drugs administered orally as solid dosage form represents the preferred class of products. Over 90% of drugs formulated to produce systemic effects are produced as solid
dosage forms
Coatings Coating is a process by which an essentially dry, outer layer of coating material is applied to the surface of a dosage form to confer specific benefits that broadly ranges from facilitating [4] product identification to modifying drug release from the dosage form .
Reasons for tablet coating The core contains a material which has a bitter taste in the mouth or has an unpleasant odour.
Coating will protect the drug from the surroundings with a view to improve its stability. Coating can modify the drug release profile, e.g., enteric coating, osmotic pump, pulsatile delivery [6].
Enteric coating An enteric coating is a barrier that controls the location of oral medication in the digestive system where it is absorbed. The word “enteric” indicates small intestine; therefore enteric coatings prevent release of medication before it reaches the small intestine. The enteric coated polymers remain unionize at low pH, and therefore remain insoluble. But as the pH increases Correspondence Sofia Konain in the GIT, the acidic functional groups are capable of ionization, and the polymer swells or Deccan School of Pharmacy, becomes soluble in the intestinal fluid. Materials used for enteric coatings include CAP, CAT, Dar-us-salam, Aghapura, PVAP and HPMCP, fatty acids, waxes, shellac, plastics and plant fibers. Nampally, Hyderabad, Telangana, India ~ 447 ~ The Pharma Innovation Journal
Polymers for enteric coating Polyvinyl derivatives polyvinyl acetate phthalate (PVAP) Polymers are substance containing a large number of Polyvinyl Derivatives Polyvinyl acetate phthalate (PVAP) structural units joined by the same type of linkage. Polyvinyl acetate phthalate (PVAP) is manufactured by the These substances often form into a chain-like structure starch, esterification of a partially hydrolyzed polyvinyl acetate with cellulose, and rubber all possess, polymeric properties. pthalic anhydride. This polymer is similar to HP-55 in stability and pH-dependent solubility. It is supply as ready-to- Classification of polymers use or ready-to-disperse enteric systems. Natural polymers Shellac Syntehtic Polymers Shellac is a polymer used in coating applications to provide Polymethacrylates (Methacrylic acid/ethyl acrylate) various functional properties. It can be used in film coatings Two forms of commercially available enteric acrylic resins to achieve enteric applications, aesthetic and immediate- are Eudragit L and Eudragit S both resins produce film that release properties, taste masking, and seal coating. Shellac is a are resistant to gastric fluid. Eudragit L and Eudragit S are natural and versatile polymer used for coating applications. soluble in intestinal fluid at pH 6 to 7 respectively. Eudragit L is available as an organic solution, solid, or aqueous Sodium alginate dispersion. Eudragit S is available as an organic solution and Sodium alginate is the sodium salt form of alginic acid and solid [4]. gum mainly extracted from the cell walls of brown algae, with Rabeprazole is a proton pump inhibitor that suppresses gastric chelating activity. In tablet formulations, sodium alginate may acid production in the stomach. Rabeprazole's mechanism of be used as both a binder and disinter grant. action involves the permanent inhibition of proton pumps in the stomach, which are responsible for gastric acid Cellulose esters production. Rabeprazole belongs to a class of antisecretory Cellulose esters have been widely used in the industry. CAP compounds that do not exhibit anticholinergic or histamine has the disadvantage of dissolving only above the pH 6, and H2-receptor antagonist properties but suppress gastric acid possibly delaying the absorption of drugs. HPMCP-50, secretion by inhibiting the gastric H+/K+ATPase at the 55,55S these are derived from Hydroxy propyl cellulose, secretory surface of the gastric parietal cell. these polymers dissolves at low pH (5 to 5.5) than CAP or acrylic co-polymers. 2. Materials and Methods Materials
Table 1: List of Ingredients
S. No. Materials Category Suppliers 1 Rabeprazole Proton Pump Inhibitors Reddy Laboratories, Hyderabad 2 Micro Crystalline Cellulose Diluent S.D.Fine Chem.Ltd,Mumbai,India 3 Cross Providone Superdisintegrant S.D.Fine Chem.Ltd,Mumbai,India 4 Crosscarmellose Sodium Superdisintegrant Myl Chem.Ltd,Mumbai,India 5 Sodium Starch Glycolate Superdisintegrant Myl Chem.Ltd,Mumbai,India 6 Magnesium Stearate Lubricant S.D.Fine Chem.Ltd,Mumbai,India 7 Starch Binder Essel Fine Chem. Mumbai 8 Lactose Monohydrate Filler Essel Fine Chem. Mumbai 9 Aerosil Glidant Myl Chem.Ltd,Mumbai,India 10 Eudragit L 100 (%W/W) Film Former S.D.Fine Chem.Ltd,Mumbai,India 11 Hpmc Hydrophilic Polymer S.D.Fine Chem.Ltd,Mumbai,India 12 Sodium Alginate Release-Retarding Agent S.D.Fine Chem.Ltd,Mumbai,India 13 Shellac Polymer Myl Chem.Ltd,Mumbai,India 14 Acetone Solvent Myl Chem.Ltd,Mumbai,India
Experimental Methods Preparation of 6.8pH phosphate buffer Determination of λmax of Rabeprazole Dissolve 28.80g of disodium hydrogen phosphate and 11.45g Standard Stock solution: 100 mg of Rabeprazole was of potassium dihydrogen phosphate in sufficient water to dissolved in 100 ml of pH 6.8 phosphate buffer (1000 μg/ml) produce 1000ml. Scanning: From the stock solution 10μg/ml was prepared in methanol and UV scan was taken between 200 to 400 nm. Calibration curve of rabeprazole in 6.8pH phosphate The absorption maximum was found to be 282 nm and was buffer used for the further analytical studies. From the standard stock solution (1000 μg/ml), appropriate aliquot were transferred to series of 10 ml volumetric flasks Calibration curve of rabeprazole in 0.1N HCL and made up to 10 ml with 6.8pH phosphate buffer so as to From the standard stock solution (1000 μg/ml), appropriate get concentration of 4, 8, 12,16 and 20 μg/ml. the absorbance aliquot were transferred to series of 10 ml volumetric flasks of the solution were measured at 282nm. This procedure was and made up to 10 ml with 0.1 N HCL, so as to get performed in triplicate to validate calibration curve. A concentration of 4, 8, 12,16 and 20 μg/ml. the absorbance of calibration graph was plotted. the solution were measured at 282nm. This procedure was performed in triplicate to validate calibration curve. A Formulation development of rabeprazole enteric coated calibration graph was plotted. tablets An ideal mixture of powder is directly punched into tablets ~ 448 ~ The Pharma Innovation Journal
weighing about 200 mg containing 20 mg of Rabeprazole, using rotary tablet compression machine.
Table 2: Compilation of Rabeprazole core Tablets
Formulation(mg) F1 F2 F3 F4 F5 F6 F7 F8 F9 Rabeprazole 20 20 20 20 20 20 20 20 20 Sodium starch glycolate 5% 7.5% 10% Cross povidone 5% 7.5% 10% Cross caramellose sodium 5% 7.5% 10% Starch 4% 4% 4% 4% 4% 4% 4% 4% 4% Lactose monohydrate Qs Qs Qs Qs Qs Qs Qs Qs Qs Aerosil 2.5% 2.5% 2.5% 2.5% 2.5% 2.5% 2.5% 2.5% 2.5% Magnesium stearate 2% 2% 2% 2% 2% 2% 2% 2% 2% Total weight 200 200 200 200 200 200 200 200 200
Table 3(a): Enteric Coating Formulation
Ingredients EC1 EC2 EC3 EC4 EC5 EC6 EC7 EC8 Eudragit L 100 (%W/W) 2% 4% 6% 8% - - - - HPMC - - - - 2% 4% 6% 8% Sodium alginate ------Shellac ------Acetone QS QS QS QS QS QS QS QS
Table 3(b): Enteric coating formulation
Ingredients EC9 EC10 EC11 EC12 EC13 EC14 EC15 EC16 Eudragit L 100 (%W/W) ------HPMC ------Sodium alginate 2% 4% 6% 8% - - - - Shellac - - - - 2% 4% 6% 8% Acetone QS QS QS QS QS QS QS QS
Rabeprazole enteric coated tablets funnel that was secured with its tip at a given height above the Rabeprazole enteric coated tablets were prepared by direct graph paper was placed on a flat horizontal surface. Granules compression technique using different excipients as well as were carefully poured through the funnel until the apex of the with varying concentrations disintegrants. conical pile just touches the tip of the funnel. The radius and height of the pile were then measured. The angle of repose () Manufacturing process for samples were calculated using the following equation [1]. 1. Co-sift Rabeprazole, Starch and Disintegrant through sieve # 30. height of the heap tan θ = 2. Sift Lactose monohydrate through sieve # 30. radius of the heap 3. Sift the Step 1 and Step 2 materials through # 30 mesh. 4. Load the step 3 materials into blender and mix for 30 Bulk Density mins. Bulk density of a compound varies substantially with the 5. Sift Aerosil through sieve # 40 along with a portion of method of crystallization, milling or formulation. Bulk prelubricated blend. density is determined by pouring pre-sieved granules into a 6. Load the step 5 material to the blender and mix for 5 graduated cylinder via a large funnel and measure the volume mins. and weight [1]. 7. Compress the lubricated blend of step no. 8 into tablets. Weight of Granules Bulk Density = Preparation of enteric coating solution: Bulk Volume of Granules 1. Disperse coating polymer in Acetone under stirring to prepare clear solution. Tapped Density 2. Add plasticizer and talc to the step no. 10 solution. Tapped density is determined by placing a graduated cylinder 3. Add color which is pre-sifted and add to the step no.11 containing a known mass of granules and mechanical tapper apparatus, which is operated for a fixed number of taps until Spray coating solutions on tablets using spray gun in coating the powder bed volume has reached a minimum volume. pan. Warm the enteric-coated tablets in coating pan at 50°C ± Using the weight of the granules in the cylinder and this 5°C for 20 -30 mins. minimum volume, the tapped density may be computed [1].
3. Evaluation Weight of Granules Tapped Density = Pre-compression Characteristics Tapped Volume of Granules Angle of Repose Angle of repose is used to determine the flow properties of Compressibility Index (CI) powders, pellets or granules. Angle of repose is the maximum Compressibility index is measured by using the values of bulk angle possible between the surface of a pile of the blend and density and tapped density. The following equation is used to the horizontal plane. Fixed funnel method was employed. A ~ 449 ~ The Pharma Innovation Journal
find the Carr’s index. assembly was positioned in the beaker containing 900ml of Water. The disintegration time of each tablet was recorded [5]. Tapped Density − Bulk Density CI = × 100 Tapped Dissolution Procedure: Drug release studies were carried out using a USP Hausner’s ratio type II dissolution test apparatus at 50rpm for 2hours in The ratio of tapped density to bulk density of powders is 900ml 0.1N HCl previously maintained at 37 °C ± 0.5 °C. 5ml called the Hausner’s ratio. It is calculated by the following of sample was taken and analyzed. equation1. After 2hrs replaced with pH 6.8 and tested for drug release for Tapped Density 12hrs at same temperature and rotation speed. 5ml of aliquots Hausner′s Ratio = Bulk Density were withdrawn at pre-determined time intervals and an equal amount of the medium will be replaced to maintain sink Post-Compression Characteristics conditions. The aliquots were diluted suitably, and the amount Weight Variation of drug released will be determined by U.V method. The USP weight variation test will be run by weighing 20 tablets individually, calculating the average weight, and 4. Results And Discussions comparing the individual tablet weights to the average [2]. Ultraviolet Visible (Uv-Visible) Spectroscopy Drug sample showed wavelength of maximum absorption (λ- Weight of Tablet − Average Weight max) 282 nm Weight Variation = × 100 Weight of Tablet − Average Weight
Weight variation should not be more than 7.5%.
Table 4: Weight Variation Tolerances for Uncoated Tablets
Average Weight of Maximum Percentage S. No. Tablets (mg) Difference Allowed 1 80 or less 10 2 80 to 250 7.5 3 More than 250 5
Thickness and diameter The thickness of a tablet will be the only dimensional variable related to the process. 10 tablets were measured for their thickness and diameter with Vernier calipers, Thickness 3 Gauge. Average thickness and diameter were calculated . Fig 1: λ-max of Rabeprazole
Hardness Standard Graph of Rabeprazole (0.1 N Hcl): Hardness of the tablets will be determined by Varian The standard graph of RABEPRAZOLE has shown good Hardness Tester and the hardness should be found within the linearity with R2 values 0.998 in 0.1 N Hcl and which range of 3.5-5.5 kg/cm². A tablet is placed between the anvils suggests that it obeys the “Beer-Lambert’s law”. and the crushing strength which causes the tablet to break is 4 recorded . Table 5: Standard Graph Readings
Friability Concentration Absorbance at 282nm The friability of tablets will be determined by Electrolab EF- 0 0 2 0.202 2, Friabillator. 20 tablets were taken and weighed. After 4 0.395 weighing the tablets were placed in the Electrolab EF-2, 6 0.558 Friabillator and subjected to the combined effects of abrasion 8 0.745 and shock by utilizing a plastic chamber that revolves at 25 10 0.912 rpm, dropping the tablets from a distance of six inches with each revolution. After operation the tablets were de-dusted and reweighed5. Friability is determined by using below equation: W F = 100(1 − 0⁄ ) Wt
Where, W0= weight of tablets before friability test. Wt= weight of tablets after friability test.
Disintegration test Disintegration testing of coated dosage forms was carried out in the six tablets basket rack USP disintegration apparatus.
One tablet was introduced into each tube of the basket rack assembly of the disintegration apparatus without disc. The Fig 2: Calibration Curve for Rabeprazole in 0.1N Hcl at 282nm
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Standard Graph of Rabeprazole in 6.8pH phosphate buffer: The standard graph of RABEPRAZOLE has shown good linearity with R2 values 0.999 and, which suggests that it obeys the “Beer-Lambert’s law”.
Table 6: Standard Graph Readings in 6.8 PH Buffer
Concentration Absorbance 0 0 2 0.156 4 0.290 6 0.419 8 0.580
10 0.718 Fig 3: Calibration Curve for Rabeprazole in 6.8 pH Phosphate Buffer at 28
Drug - excipients compatibility studies By Ft-Ir
Fig 4: FTIR Spectra of Rabeprazole
Fig 5: FTIR of rabeprazole optimized formulation
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Evaluation of pre compression parameters for enteric coated tablets of rabeprazole
Table 7: Precompression data of rabeprazole core tablet
Formulations Angle of Repose (θ) Loose Bulk Density (g/ml) Tapped Bulk Density (g/ml) %Compressibility Hausner’s ratio F1 27.520.15 0.44±0.04 0.50 ± 0.04 12.00±0.6 1.13±0.04 F2 28.400.11 0.44±0.05 0.50 ± 0.1 12.00±0.4 1.13±0.02 F3 28.310.13 0.43±0.045 0.51± 0.04 15.68±0.8 1.18±0.08 F4 25.340.13 0.45±0.044 0.52± 0.01 13.46±0.1 1.15±0.06 F5 26.100.12 0.43±0.045 0.51 ± 0.04 15.68±0.6 1.18±0.08 F6 29.670.19 0.42±0.044 0.50 ± 0.09 16.00±0.8 1.19±0.09 F7 28.33±0.2 0.47±0.02 0.53±0.05 11.32±0.8 1.12±0.09 F8 25.66±0.14 0.45±0.03 0.56±0.05 19.64±0.05 1.24±0.05 F9 28.540.19 0.51±0.045 0.59 ± 0.04 13.55±0.07 1.15±0.06
Angle of repose Compressibility index Angle of repose values for batch F1 –F9 falls within the range The percentage compressibility for the batch F1- F9 was of 25-30, and the flow property was found to be good. found in to be within the range 17 and the flow property was found to be excellent. Bulk and Tapped Density The bulk density value for the formulated blend was found to Hausner’s ratio be within the range of 0.4 to 0.5 gm/ml, where as the tapped The Hausner’s ratio value for the batch F1 –F9 falls within density was found to be within the range of around 0.5 to the range of 1.11-1.26 and found to have good flow property. 0.6gm/ml.
Table 8: Post Compression Parameters of Core Tablet
Formulations Weight variation (mg) Hardness (Kg/cm2 ) Thickness (mm) Friability (%) Assay % (W/W) F1 200 ± 0.04 3.40 ± 0.2 2.5 ± 0.01 0.43 ± 0.11 100.3± 0.21 F2 202 ± 0.02 3.62 ± 0.1 2.2 ± 0.04 0.45 ± 0.12 100.1± 0.16 F3 201 ± 0.04 3.50 ± 0.2 2.8 ± 0.01 0.49 ± 0.12 100.8± 0.16 F4 199 ± 0.05 3.43 ± 0.3 2.3 ± 0.04 0.50 ± 0.11 99.0± 0.19 F5 200 ± 0.05 3.44 ± 0.3 2.2 ± 0.03 0.31 ± 0.12 98.9± 0.19 F6 202 ± 0.02 3.47 ± 0.2 2.1 ± 0.04 0.32 ± 0.12 99.4± 0.21 F7 201 ± 0.02 3.49 ± 0.1 2.6 ± 0.06 0.19 ± 0.11 100.6± 0.16 F8 199 ± 0.04 3.50 ± 0.2 2.2 ± 0.03 0.16 ± 0.12 100.2± 0.16 F9 201 ± 0.03 3.50 ± 0.1 2.0 ± 0.02 0.29 ± 0.12 99.5± 0.16
Hardness The Hardness of the formulated batch F1 to F9 was maintained in the range 3.4 to 3.6 Kg/cm2.
Percentage friability The percentage friability for the formulated batches F1 to F9 was found to be within the range i.e, NMT 1% w/w.
Assay For the entire formulated batch from F1-F9 the assay value was found to be within the limits of 90-110% w/w.
Weight variation The weight variation values for all the formulated batch F1 to F9 was found to be within the 5% acceptable limits.
In vitro dissolution studies Fig 6: Percentage CDR of rabeprazole core tablet
Table 9: Dissolution Data of Rabeprazole Core Tablet In F9 formulation the concentration of Crospovidone was
Time F1 F2 F3 F4 F5 F6 F7 F8 F9 optimized and found to have good flow property, and releases 6.8pH phosphate buffer 99.9% of drug. 15min 22.8 38.3 14.5 33.4 58.2 50.8 33.8 54.3 50.2 30min 45.3 52.8 38.9 52.1 75.6 76.1 68.2 92.4 80.1 Evaluation parameters for enteric coated tablets 45 min 62.1 72.6 59.2 66.8 90.9 92.4 91.6 95.6 99.9 F9 formulation with highest drug release was selected for 60min 75.8 85.1 70.4 79.2 95.8 98.4 98.9 99.2 99.9 coating. Four different coating polymers were used in four different concentrations.
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Table 10: Post compression data of rabeprazole enteric coated tablet
Formulations Weight variation Hardness Thickness (mm) Friability (%) Acid resistance time Assay%(w/w) EC 1 205 ± 0.05 3.5 ± 0.2 2.4 ± 0.05 0.44 ± 0.14 2hrs 95.3 ± 0.16 EC 2 205 ± 0.07 3.5 ± 0.1 2.4 ± 0.07 0.44 ± 0.12 2hrs 97.1 ± 0.17 EC 3 205 ± 0.04 3.5 ± 0.3 2.4 ± 0.1 0.44 ± 0.14 2hrs 99.9 ± 0.16 EC 4 205 ± 0.09 3.5 ± 0.1 2.4 ± 0.14 0.44 ± 0.16 2hrs 93.8 ± 0.19 EC 5 204 ± 0.1 3.5 ± 0.3 2.3 ± 0.03 0.55 ± 0.11 2hrs 99.9 ± 0.21 EC 6 204 ± 0.08 3.5 ± 0.05 2.3 ± 0.06 0.55 ± 0.15 2hrs 98.4 ± 0.20 EC 7 204 ± 0.05 3.5 ± 0.1 2.3 ± 0.08 0.55 ± 0.13 2hrs 95.6 ± 0.21 EC 8 204 ± 0.07 3.5 ± 0.07 2.3 ± 0.12 0.55 ± 0.16 2hrs 99.2 ± 0.19 EC 9 208 ± 0.09 3.5 ± 0.04 2.6 ± 0.01 0.48 ± 0.1 2hrs 95.3 ± 0.15 EC10 208 ± 0.11 3.5 ± 0.3 2.6 ± 0.05 0.48 ± 0.13 2hrs 96.6 ± 0.17 EC11 208 ± 0.15 3.5 ± 0.18 2.6 ± 0.09 0.48 ± 0.17 2hrs 97.2 ± 0.17 EC12 208 ± 0.13 3.5 ± 0.15 2.6 ± 0.18 0.48 ± 0.20 2hrs 97.9 ± 0.16 EC13 210 ± 0.18 3.5 ± 0.5 2.8 ± 0.03 0.45 ± 0.08 2hrs 93.2 ± 0.20 EC14 210 ± 0.06 3.5 ± 0.17 2.8 ± 0.08 0.45 ± 0.11 2hrs 94.8 ± 0.21 EC15 210 ± 0.05 3.5 ±0.06 2.8 ± 0.15 0.45 ± 0.15 2hrs 97.8 ± 0.16 EC16 210 ± 0.1 3.5 ±0.05 2.8 ± 0.2 0.45 ± 0.17 2hrs 99.2 ± 0.20
Dissolution study for enteric coated tablet
Table 11(a): Dissolution profile for rabeprazole enteric coated tablet
Time EC1 EC2 EC3 EC4 EC5 EC6 EC7 EC8 0.1 NHCL 5 min 0 0 0 0 0 0 0 0 15 min 0 0 0 0 0.002 0.001 0.0046 0.0028 30 min 0 0 0 0 0.009 0.007 0.009 0.008 45 min 0 0 0 0 0.012 0.013 0.017 0.019 60 min 0 0 0 0 1.07 1.02 1.089 1.02 75 min 0 0 0 0 1.35 1.56 1.67 1.42 90 min 0 0 0 0 1.92 1.96 1.93 1.87 120 min 0 0 0 0 2 2 2 1.94 5 min 10.02 23.45 35.10 21.69 31.26 35.02 25.26 10.97 15 min 21.11 35.47 50.28 30.93 53.89 47.04 31.30 13.43 30 min 41.95 48.89 85.56 48.24 70.01 70.47 72.41 36.02 45 min 57.50 67.23 97.5 61.86 84.17 85.56 84.82 54.82 60 min 70.19 78.80 98.3 73.34 92.41 92.69 91.58 65.19 75 min 78.20 80.21 99.1 77.16 95.03 94.22 93.5 80.14 90 min 83.19 92.28 99.9 88.24 96.22 96.95 94.1 91.4 120 min 95.3 97.1 99.9 93.8 97.2 98.4 95.6 92.7
Table 11(b): Dissolution profile for rabeprazole enteric coated tablet
Time EC9 EC10 EC11 EC12 EC13 EC14 EC15 EC16 0.1NHCL 5 min 0 0 0 0 0 0 0 0 15 min 0.001 0.003 0.001 0.0049 0.002 0.006 0.009 0.01 30 min 0.045 0.09 0.035 0.08 0.02 0.07 0.08 0.04 45 min 1.02 1.04 0.98 0.95 1.03 1.39 1.56 1.07 60 min 1.67 1.52 1.24 1.27 1.78 1.95 1.87 1.57 75 min 1.98 1.96 1.76 2.14 2.01 2.05 2.09 1.89 90 min 2.06 2.13 2.19 2.86 2.23 2.65 2.5 2.5 120 min 2.45 2.73 2.98 3 2.54 2.76 2.9 2.89 5 min 10.25 15.02 22.15 25.63 30.95 31.15 23.6 20.14 15min 13.49 25.47 29.43 37.93 53.89 47.04 31.30 45.06 30min 30.17 50.89 30.02 49.24 70.01 70.47 72.41 52.19 45 min 53.90 64.23 45.82 68.46 84.17 85.56 84.82 68.23 60min 73.25 82.80 69.19 73.34 92.41 92.69 91.58 87.63 75 min 80.4 83.10 87.3 79.15 92.56 92.9 92.8 90.9 90 min 89.7 85.35 90.7 83.05 93.0 93.25 96.73 95.34 120min 95.3 96.6 97.0 97.2 93.2 94.8 97.8 96.2
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in 45 mins when compared with other formulations and the natural polymers are also equally effective with a release of 97.2% for E12 and 97.8 for EC 15.
5. Conclusion Rabeprazole enteric coated tablets were prepared by using four different enteric coating polymers. The first two polymers (synthetic) used for enteric coating are Eudragit L100 and HPMC EC1 – EC8. These were used in the concentration 2%, 4%, 6%, and 8%. The in-vitro dissolution was carried out in 0.1 N HCL for 2 hours and in 6.8 PH phosphate buffer for 2 hours. In 0.1 HCL the Eudragit L100 had zero drug release. The natural polymers used for enteric coating were Sodium
Alginate and Shellac EC9 – EC16. The natural polymers were Fig 7: Cumulative% drug release graph for formulation EC1-EC8 coated in the concentration 2%, 4%, 6%, and 8%. The in-vitro dissolution was carried out in 0.1 N HCL for 2 hours and in 6.8 PH phosphate buffer for 2 hours. When comparing the natural and synthetic polymers, it can be concluded that the in-vitro drug release showed Eudragit L100 polymer with 6% concentration had 100% release in PH 6.8 Phosphate buffer, and sodium alginate with 8% concentration and Shellac with 6% concentration exhibited good release of 97.2% and 97.8% respectively. The Eudragit L100 exhibited good performance but the natural polymers are also equally effective. Instead of using the synthetic polymers, natural polymers can be a good alternative. Out of the two natural polymers that we used, Shellac presented good performance when compared to Sodium Alginate because Enteric coating of Sodium Alginate is quite difficult and unreliable.
Fig 8: Cumulative% drug release graph for formulation EC9-EC16 6. References 1. Cooper, Gun. Size Reduction’. In: Carter SJ, editor. Tutorial Pharmacy. 6th ed. 2000, 183-91. 2. Leon Lachman, Herbert A Lieberman, Joseph L Kanig. ‘The Theory and Practice of Industrial Pharmacy’, Lea & Febiger, 1986. 3. Richard Dietrich, Maximilian Moravek, Christine Buerk, Véronique Broussolle, Marie-Hélène Guinebretière, Per Einar Granum, Christophe Nguyen-the, Erwin Märtlbauer, ‘Determination of the toxic potential of Bacillus cereus isolates by quantitative enterotoxin analyses’, FEMS Microbiology Letters, 2006; 257:293- 298. 4. Sushama Pole, Suryaprakash Maurya, Pooja Hasnale, Nitin Rathod, Sharayu Bendale, Dr. Nilesh M Khutle, ‘A Detail Understanding of Enteric Coated Tablet:
Fig 9: Cumulative% drug release graph for formulation EC3 Vs Manufacturing and Evaluation’, European Journal of EC11 Vs EC15 Pharmaceutical and Medical Research. 2016; 3(4):135- 144. Dissolution studies of all the formulations were carried 5. Singh Deep Hussan, Roychowdhury Santanu, Verma P, out using dissolution apparatus USP type Bhandari V. ‘A review on recent advances of Enteric I. The dissolution studies were conducted by using dissolution Coating’, IOSR Journal of Pharmacy. 2012; 2(6):5-11. media, 0.1 N HCl for 2hrs and 6.8 pH phosphate buffer for 6. Graham C Cole, Pharmaceutical Production Facilities – next two hours. The results of the in-vitro dissolution studies Design and Applications, Second Edition, 1998. of formulations EC1 – EC16, shown in table no.- The plots of 7. Steven W Baertschi, Karen M Alsante, Robert A Reed. Cumulative percentage drug release Vs Time. Figure -- ‘Pharmaceutical Stress Testing: Predicting Drug shows the comparison of% CDR for formulations EC1– Degradation’, Second Edition, 2005. EC16. 8. Shantha Kumar GS, Divya Bhanu Parchuri, Divakar The formulations EC3 showed a maximum release of 99.9 Goli, Roopa Karki. ‘Formulation and Evaluation of within 120 mins in 6.8pH Phosphate buffer after hours of acid Nanoparticulate Drug Delivery System of Acyclovir for resistance. Topical Drug Delivery’, World Journal of Pharmacy and Among all formulations EC 3 shows Maximum drug release Pharmaceutical Sciences, 2013; 2(6):5602-5617.
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