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  Home::FORMULATION, DEVELOPMENT AND EVALUATION OF TRAMADOL HYDROCHLORIDE MOUTH DISSOLVING TABLET
  FORMULATION, DEVELOPMENT AND EVALUATION OF TRAMADOL HYDROCHLORIDE MOUTH DISSOLVING TABLET
   

FORMULATION, DEVELOPMENT AND EVALUATION OF TRAMADOL HYDROCHLORIDE MOUTH DISSOLVING TABLET Shelke O. S., Gadhave M. V., Jadhav S. L., D. D. Gaikwad Department of Pharmaceutics, VJSM’s Vishal Institute of Pharmaceutical Education and Research, Ale, Pune, Maharashtra, India. KEY WORDS: Mouth Dissolving Tablet, Tramadol HCl, Crosspovidone, Microcrystaline cellulose, Evaluation of MDT. INTRODUCTION: Recent developments in technology have presented viable dosage alternatives for patients who may have difficulty swallowing tablets or liquids. However, some patients, particularly pediatric and geriatric patients, have difficulty swallowing or chewing solid dosage forms. Many pediatric and geriatric patients are unwilling to take these solid preparations due to fear of choking. For example, a very elderly patient may not be able to swallow a daily dose of antidepressant. MDTs disintegrate and/or dissolve rapidly in the saliva without the need for water. Some tablets are designed to dissolve in saliva remarkably fast, within a few seconds, and are true fast-dissolving tablets. Others contain agents to enhance the rate of tablet disintegration in the oral cavity, and are more appropriately termed fast-disintegrating tablets. Tramadol hydrochloride is a centrally acting opioid analgesic structurally related to codeine and morphine used in the treatment of moderate to severe pain in diverse conditions. Combined with low dependence/abuse potential, it has proven to be of significant advantage over other agents, especially in the elderly. Tramadol hydrochloride has been proved to be effective in both experimental and clinical pain without causing serious cardiovascular or respiratory side effects Mouth disintegrating tablets (MDTs) are a perfect fit for all of these patients. Fast-dissolving drug delivery systems have rapidly gained acceptance as an important new way of administering drugs. There are multiple fast-dissolving OTC and Rx products on the market worldwide, most of which have been launched in the past 3 to 4 years. There have also been significant increases in the number of new chemical entities under development using a fast-dissolving drug delivery technology. ADVANTAGES OF MDT 1. Improved patient compliance 2. Rapid onset of action and may offer an improved bioavailability. 3. Patient having difficulty in swallowing tablet can easily administer this type of dosage form 4. Useful for pediatric, geriatric and psychiatric patients 5. Suitable during traveling where water is may not be available 6. Gives accurate dosing as compared to liquids 7. Good chemical stability. 8. Free of need of measuring, an essential drawback in liquids. SALIENT FEATURES OF FAST DISSOLVING DRUG DELIVERY SYSTEM • Ease of administration for patients who are mentally ill, disabled and uncooperative. • Requires no water • Quick disintegration and dissolution of the dosage form. • Overcomes unacceptable taste of the drugs. • Can be designed to leave minimal or no residue in the mouth after administration and also to provide a pleasant mouth feel. • Allows high drug loading. • Ability to provide advantages of liquid medication in the form of solid preparation. • Adaptable and ameanable to existing processing and packaging machinery • Cost- effective MATERIAL AND METHOD: Tramadol HCl is obtained as gift sample from Marksans Pharma Ltd. Other excipients are of USP grades and are obtained as gift samples like Microcrystalline Cellulose, Lactose Monohydrate , Sodium Starch Glycolate , Crosscarmellose sodium, Crosspovidone, Colloidal Silicon Dioxide, Orange Flavor, Aspartame, Magnesium Stearate. PREFORMULATION STUDIES: Preformulation testing is the first step in the rational development of dosage form of a drug substance. It can be defined as investigation of physical and chemical properties of a drug substance alone and when combined with excipients. The overall objective of pre-formulation testing is to generate information useful to the formulator in the developing stable. 1. Active Pharmaceutical Ingredient (API) Characterization: A) Evaluation of API B) Bulk Characterization A) Evaluation of API: a) Organoleptic properties b) Analytical Evaluation Sr. No. Ingredient Formulation F1 F2 F3 F4 F5 F6 1 Tramadol HCl 50 50 50 50 50 50 2 MCC (AVICEL 102) 40 40 40 40 40 40 3 Lactose Monohydrates ( SuperTab 11SD) 90.5 90.5 90.5 80.5 80.5 80.5 4 Sod. Starch Glycolate 10 - - 20 - - 5 Cross Carmellose Sodium - 10 - - 20 - 6 Crosspovidone - - 10 - - 20 7 Aerosil 200 4 4 4 4 4 4 8 Sacchrine Sodium 1 1 1 1 1 1 9 Orange Flavour 1.5 1.5 1.5 1.5 1.5 1.5 10 Magnesium Stearate 3 3 3 3 3 3 11 Total 200 200 200 200 200 200 Table No.1 Formulation of Tramadol HCl Mouth Dissolving Tablet Preapaeration of Tablets Tramadol HCl was mixed with excipients according to respective formulation like Microcrystalline Cellulose, Lactose Monohydrate , Sodium Starch Glycolate , Crosscarmellose sodium, Crosspovidone, Colloidal Silicon Dioxide, Orange Flavor, Aspartame. This bulk is blended for 10 min at 10 min in Kalveka Bin Blender. Magnesium Stearate was added into it and lubricated for 3 min at 10 min in Kalveka Bin Blender. Evaluation of Mouth Dissolving Tablet 1. Description Rouned tablet with embossing ‘269’ on one side and ‘G’ on another side 2. Weight Variation Tablets of each of formulation were weighed individually using an electronic balance. The average weight was calculated and individual tablet weight was compared with average value and the deviation was recorded. The percentage deviation for weight uniformity of tablets as per USP limits. 3. Tablet Hardness Tablet hardness is also known as tablet crushing strength. Dr. Schleuniger tester was used. It applies force to the tablet diametrically with the help of an in built spring. Triplicate determinations were done. The hardness of the tablet is measured by using conventional hardness testers like Dr. Schleuniger tester tester. The limit is toward the lower range in order to help early disintegration in mouth. 4. Friability Test Roche Friabilator was used for the purpose. Compressed tablets should not lose more than 1% of their weight (as per USP) It is a difficult job to maintain the percentage of friability within the limit, since all the methods of preparation of orodispersible tablets have a tendency to increase the percentage of friability. In all aspect, the range is within limit of 0.1%-0.9%. Roche friabilator is used in conventional form in order to measure friability of thetablets. 5. Thickness The thickness of tablets was determined using Digital Vernier Caliper, (Mitutoyo, Japan). It is expressed in mm. 6. In-vitro Disintegration Time The disintegration time of the tablet was measured in water (37±2°C) according to USP disintegration test with disk. Six tablets from every batch (formulation) were tested for the disintegration time. The in-vitro disintegration time was determined using disintegration test apparatus. A tablet was placed in each of the six tubes of the apparatus. The time in seconds taken for complete disintegration of the tablet with no palatable mass remaining in the apparatus was measured in seconds. 7. Content Uniformity Ten tablets from each batch were powdered. Then powdered sample equivalent to 100mg of drug was transferred to a volumetric flask. Powder equivalent to 100 mg of Drug was dissolved in 0.1 N HCl. 1 ml of filtrate was further diluted to 100 ml with 0.1 N HCl and it was determined by spectroscopy at 271 nm. 8. Wetting Time This is carried out as a measure of hydrophilicity of tablets . Wetting time is a length of time required to wet the tablet. Apiece of tissue paper (12 x 10.75) was folded and placed in small petridish (I.D.=6.5cm) containing 6 ml of simulated saliva. Tablet was put on the paper and time required for complete wetting was measured. Three trials for each batch was performed and standard deviation was determined. A piece of tissue paper folded twice was placed in a small petridish (ID=6.5cm) containing 6 ml of simulated saliva pH 7.4, a tablet was put on the paper, and the time for complete wetting was measured. Three trials for each formulation was performed. 9. In-Vitro dissolution Studies The in-vitro dissolution study was carried out using 0.1 N HCl as dissolution medium with 100 rpm speed using USP Type-II dissolution apparatus. The study was carried out in 900 ml of 0.1N HCl for 1 Hours maintained at 37 ± 0.5°C. At the end 5 ml of sample is withdrawn replenish with equal volume of 0.1 N HCl. Time points 1, 2, 3, 5, 10, 15, 30, 45,60 min. RESULT AND DISCUSSION Evaluation of Tablets Tablets prepared by direct compression method were found to be good, without any chipping, capping and sticking. The Evaluation parameter of fast dissolving tablets was studied and shown in Table 3. Sr. No. B.D. T.D. Carr’s Index Hausner ratio Melting Points Water by KF 1 0.27 0.52 48.07% 1.92 2830 C 1.93 2 0.28 0.53 47.16% 1.89 2840 C 1.97 Table No. 2 Bulk Characterization of Tramadol HCl Formulation Hardness Friabilty(%) Thickness mm Content Uniformity % Drug Content Wetting Time(Sec) F1 4.5 0.15 3.6 101 95.2 50 F2 4.2 0.05 3.66 98.1 99.9 47 F3 3.8 0.045 3.59 96.4 100.8 48 F4 4.1 0.08 3.65 98.9 95.9 52 F5 4.3 0.06 3.66 100 95.4 45 F6 3.9 0.04 3.7 100.9 99.5 27 Table No. 3 Evaluation of Mouth Dissolving tablet Time % Cumulative Drug Release 0.1N HCl , USP-II, 900ml, 100 RPM min F1 F2 F3 F4 F5 F6 1 70 60 64 72 70 75 2 81 71 78 85 80 89 3 93 82 84 94 91 98 4 99 89 91 106 97 100 5 100 96 97 106 99 101 10 100 100 100 107 105 101 Table No. 4: In-Vitro dissolution study of Tramadol HCl Tablet. Figure No. 1: In-Vitro dissolution study of Tramadol HCl Mouth Dissolving Tablet. Batch No. F6 Initial 1M 40/75 2M 40/75 3M 40/75 Stability incubation date 05-04-2013 Dissolution Medium 0.1N HCl USP-II, 100 RPM,900ml Time Point % Release 1 68 65 67 65 2 87 84 83 85 3 95 98 97 97 4 97.1 96.2 96.8 96.6 5 68 65 67 65 10 97.1 96.2 96.8 96.6 15 98.8 97.9 100. 101 Assay (%) 99.3 101 99.7 98.6 Table No. 5: The stability studies of final formulation F2H in HDPE in 40˚C75%RH for 1st, 2nd and 3rd month. Batch No. F6 Initial 1M 25/60 2M 25/60 3M 25/60 Stability incubation date 05-04-2013 Dissolution Medium 0.1N HCl USP-II, 100 RPM,900ml Time Point % Release 1 68 66 67 67 2 87 87 86 85 3 95 96 97 98 4 97.1 96.2 97.8 98.6 5 68 66 67 67 10 97.1 96.2 96.8 96.6 15 98.8 97.9 100. 101 Assay (%) 97.1 96.2 97.8 98.6 Table No. 6: The stability studies of final formulation F2H in HDPE in 25˚C/60%RH for 1st, 2nd and 3rd months REFERENCES:  Raja S, Vedavathi T. Recent Trends of Oral Fast Disintegrating Tablets-An Overview of Formulation. 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Date: 26, Aug 2013 Posted By: OM SHELKE
   
 
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