International Journal of Innovative Pharmaceutical Sciences and Research

Transcription

1 International Journal of Innovative Pharmaceutical Sciences and Research FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF IBUPROFEN 1 K.Vinay Kumar*, 1 V. Swetha Kruthika, 1 C.V.S Raghu Kiran Department of Pharmaceutics, Teegala Krishna Reddy College of Pharmacy, INDIA Abstract The aim of present investigation was to prepare fast dissolving tablets of anti-inflammatory drug Ibuprofen. The solubility of poorly soluble drug was enhanced by preparing solid dispersions of the drug with Urea in various concentrations. The optimized solid dispersions (Drug: Urea, 1:1 ratio) were further kneaded with suitable proportions of superdisintegrants such as; Crosscarmellose, Sodium starch glycolate and Crosspovidone. Fast dissolving tablets of Ibuprofen was prepared by direct compression method. The pre-compressive parameters for the blends and post-compressive parameters for the prepared tablets were evaluated. All formulations showed desired pre and post-compressive characteristics. Short term accelerated stability study was performed for optimized formulation. FTIR study showed no evidence of drug-excipient interaction. The optimized formulation was found to be F6. It was concluded that fast dissolving tablets of Ibuprofen can be prepared by solid dispersions of drug with Urea and combination of two superdisintegrants provide complete and better dissolution within in shorter period of time. Hence effective for geriatric, pediatric, mentally ill, bedridden and patients, who do not have easy access to water. Keywords: Ibuprofen, Urea, Solid dispersions, Superdisintegrants. Corresponding Author K.Vinay Kumar Department of Pharmaceutics, Teegala Krishna Reddy College of Pharmacy, INDIA vinayoct0@gmail.com Phone: Available online: May Issue 509

2 INTRODUCTION [1,,] Drug Delivery Systems (DDS) are a strategic tool for expanding markets/indications, extending product life cycles and generating opportunities. Drug delivery systems are becoming increasingly sophisticated as pharmaceutical scientists acquire a better understanding of the physicochemical and biochemical parameters pertinent to their performance. The oral route remains the perfect route for the administration of therapeutic agents because of low cost of therapy, ease of administration, accurate dosage, self medication, pain avoidance, versatility, leading to high levels of patient compliance. Improved patient compliance has achieved enormous demand. To develop a chemical entity, a lot of money, hard work and time are required. So focus is rather being laid on the development of new drug delivery systems for already existing drugs, with enhanced efficacy and bioavailabilities, thus reducing the dose and dosing frequency to minimize the side effects, enhance the safety of a drug molecule while maintaining its therapeutic efficacy. Recent advances in Novel Drug Delivery Systems (NDDS) aim for the same by formulating a dosage form, convenient to be administered so as to achieve better patient compliance. Pharmaceutical technologists have put in their best efforts to develop a Fast Dissolving Drug Delivery System. MATERIALS AND METHODS: Ibuprofen, urea, Sodium starch Glycolate, Crosspovidone, Crosscarmellose sodium and starch, Camphor, Saccharin sodium, magnesium stearate, purified Talc. Preparation of solid dispersions [4] Solid dispersions of ibuprofen were prepared with carrier (urea) in 1:0.5 (S1), 1:1 (S) and 1: (S) weight ratios by solvent evaporation method by the procedure given below. Calculated quantity of drug was dissolved in ethanol and mixed with urea different ratios. The mixture was stirred with a glass rod for 15 minutes and evaporated to dryness for 48 hours in a desiccator at room temperature to remove the solvent. The powder was passed through sieve no#60 and stored in airtight container for further studies. Preparation of fast dissolving tablets Preparation of fast dissolving tablets required quantity of optimized solid dispersions (drug: polymer, 1:1 ratio) was triturated with different proportions of Superdisintegrants via Crosscarmellose, Sodium starch glycolate and Crosspovidone. Mixed with other ingredients such as starch (filler) saccharin (sweetener) and camphor (sublimating agent) in geometric ratio of their Available online: May Issue 510

3 weight and powdered in a mortar. The blend was transferred to a poly bag; purified talc and magnesium stearate were added and mixed for 10 minutes. The blend was directly compressed to obtained flat rounded tablets weighing ~150mg. PRE-FORMULATION STUDIES Physical appearance The appearance of the active pharmaceutical ingredient was done by visual observation. A small quantity of Ibuprofen drug taken in a butter paper and viewed in well illuminated place. Solubility Small amount of drug is taken and dissolved in different solvents like distilled water, 0.1N HCL, 0.1N NaOH, 6.8 ph Buffer and determine the solubility of drug substance. Determination of λmax absorbance of Ibuprofen A known (0ug/ml) concentration of drug solution was prepared. And to determine the absorbance values in between nm. Then one specific nm value show more absorbance then this is the max absorbance of the drug substance. Determination of standard calibration curve of ibuprofen in 0.1N NaOH Take 100mg powder of Ibuprofen and dissolve in 100ml of 0.1N NaOH. This is stock solution. Now pipette,4,6,8 & 10 ml from above solution and dilute up to 100ml. Measure the absorbance at 5 nm using UV visible spectrometer and plot the graph of concentration versus absorbance. Drug-Excipients Compatibility Studies Drug-excipient compatibility studies were performed for physical mixtures of drug with various excipients in 1:1 ratio. This blend was placed in closed glass vials held at 40ºc/75% RH. This sample was withdrawn at the end of 4 th week and subjected to FTIR studies over a range of nm. The peak of physical mixer was then correlated with the peaks of the pure drug. EVALUATION OF SOLID DISPERSIONS [5] Aqueous solubility studies It was carried out to determine solubility of Ibuprofen alone in aqueous medium and also in presence of carrier urea. This was done by dissolving excess drug in different flasks containing different concentration of carrier in distilled water. The flasks were shaken thoroughly for 6 hours and kept aside for 4hours. The suspensions were filtered, diluted suitably and absorbance was measured at 5nm. Available online: May Issue 511

4 Drug content Solid dispersion equivalent to 100mg of drug was accurately weighed and dissolved in 1000ml of 0.1 N NaOH, from that 1ml of solution was diluted to 10ml 0.1 N NaOH and assayed for drug content by spectrophotometric method. EVALUATION OF PRE-COMPRESSIVE PARAMETERS [6,7, 8] Angle of repose (θ) Angle of repose is defined as the maximum angle possible between the surface of a pile of the powder and horizontal plane. The frictional force in a loose powder or granules can be measured by angle of repose. Bulk Density Tan θ = h / r θ = tan -1 (h/r) Bulk density is determined by pouring powder into a graduated cylinder via a large funnel and measure the volume and weight. Tapped Density Compressibility Index Bulk Density = weight of sample/ Bulk volume of the sample Tapped Density = weight of sample/tapped volume of the sample Compressibility Index [%] = Tapped density Bulk density / Tapped density X 100 Haussner s ratio Haussner s ratio = ρt/ρ Where ρt = tapped density ρb = bulk density EVALUATION OF POST-COMPRESSIVE PARAMETERS: All the formulations of Ibuprofen prepared tablets were evaluated for the following physical and chemical parameters. Physical appearance Size and shape The tablets formulated shape done by visual observation. Size was calculated by Vernier calipers. Colour The appearance of the Ibuprofen fast dissolving tablets were done by visual observation. Available online: May Issue 51

5 Hardness test [9] Tablets require a certain amount of strength, or hardness and resistance to friability, to withstand mechanical shocks of handling in manufacture, packaging and shipping. The hardness of the tablets was determined using Monsanto Hardness tester. It is expressed in Kg/cm. Friability test Roche Friabilator was used for testing the friability using the following procedure. Twenty tablets were weighed accurately and placed in the plastic chamber that revolves at 5 rpm for 4minutes dropping the tablets through a distance of six inches with each revolution. After 100 revolutions the tablets were reweighed and the percentage loss in tablet weight was determined. % F = Initial weight Final weight / Initial weight X 100 % Friability of tablets less than 1% is considered acceptable. Weight variation test The tablets were selected randomly from each formulation and weighed individually to check for weight variation. Twenty tablets were weighed individually and the average weight was determined. Then percentage deviation from the average weight was calculated. The % weight variation was calculated with the following formula. %Weight variation= (Average weight- individual weight) / individual weight 100 Drug content uniformity [10] Twenty tablets were weighed and crushed in a mortar. Then weighed powder contain equivalent to 100mg of drug transferred in 100ml of 0.1 N NaOH. Its concentration 1000 ug/ml. 10ml from this stock solution taken and diluted to 100ml of 0.1N NaOH, it makes 100μg/ml. Then take ml from stock solution and diluted to 10ml of 0.1N NaOH it makes 0 μg/ml. Absorbance measure at 5nm and compare with standard calibration curve. Wetting time A piece of paper folded twice was kept in a Petri dish containing 6 ml of purified water containing amaranth dye. A tablet was placed on the tissue paper. The time required to develop a color on the upper surface of the tablet was recorded as the wetting time. Disintegration test The disintegration time for all formulations was carried out using tablet disintegration test apparatus. Six tablets were placed individually in each tube of disintegration test apparatus. The water was maintained at a temperature of 7 ± C and time taken for the entire tablet to disintegrate completely was noted. Available online: May Issue 51

6 In vitro dissolution studies [11] In vitro dissolution studies are performed by using USP dissolution test apparatus using 6.8 phosphate buffers as dissolution medium. The paddles are allowed to rotate at speed of 50 rpm. The dissolution medium was maintained at a temperature of 7±0.5 ºC and samples are withdrawn at an interval of every 5 min. The volume of the withdrawn samples is replaced by fresh dissolution medium in order to keep the volume of the dissolution medium as constant. The withdrawn samples were filtered and absorbance was measured at absorption maxima of 5 nm using UV-visible spectrophotometer. RESULT &DISCUSSION Preformulation studies of drug The colour of Ibuprofen was observed as the white to partially crystalline powder. Drug Slightly soluble Distilled water and 0.1 N HCL.Completely soluble in 0.1 N NaOH and 6.8 ph Buffer. Melting point of Ibuprofen is determined by capillary tube method. Then melting point of Ibuprofen is 79ºC was observed. The Max absorbance of Ibuprofen found to be 5nm.Standard calibration curve of ibuprofen done. Result of drug excipients compatibility studies The FTIR data of drug with excipients was superimposable with the peaks of pure Ibuprofen drug. Thus the FTIR studies confirmed that there were no drug-excipient interactions. Evaluation of solid dispersions The results of the evaluation of solid dispersions were indicated the S formulation is better for the processing of formulation of tablets. Evaluation of tablets Angle of repose The results of the table No 6.6indicate that the drug powder was ready to filling showing fair to good flowability with the angle of repose values ranging from 8º.68 to º.61. Flow properties The flow properties (Bulk density, Tapped density, carr s index/compressibility index) of the drug powder ready for compression were determined. Post-compression parameters studies The post compression parameters like average weight, hardness, thickness, % friability, drug content and disintegration time were evaluated. The hardness of the all the tablets was found to be Available online: May Issue 514

7 within the range of.5-.5 KP. The thickness of the tablets was observed to be 4.00 mm. Thus this data demonstrated the uniformity in thickness, hardness and weight of the tablets. The friability of the all the formulations was found to be less than 1 % and hence the tablets can withstand the mechanical stress during handling and storage. The tablets showed a disintegration requirement that is less than 0 sec which is better to the formulations. Cumulative drug percentage of Ibuprofen tablets studies All the formulations of Ibuprofen were subjected to drug release to according to official method. The % drug release profiles of all the formulations were compared with each other. The effect of concentration of super disintegrating agent on the drug release of Ibuprofen was studied. Good correlation was observed between the concentration of superdisintegrant and rate of the dissolution studies. The results indicated that the formulation prepared with the combination of Sodium starch glycolate and Crosscarmellose was found to be optimized which provides maximum drug release (98.6 %) and minimum disintegration time ( sec). Table 1: Solubility of drug Solvent Solubility Distilled water Slightly soluble 0.1 N HCL Slightly soluble 0.1 N NaOH Soluble 6.8 ph BUFFER Soluble Fig.1: Max absorbance of Ibuprofen Available online: May Issue 515

8 %Transmittance RESEARCH ARTICLE K.Vinay Kumar et.al / IJIPSR / (5), 015, Fig. : Calibration curve of ibuprofen in 0.1 N NaOH at 5 nm Fig. : FTIR Spectra of Ibuprofen IBUPROFEN with excipients Wavenumber Fig.4: FTIR Spectra of Drug with Excipients Available online: May Issue 516

9 Table : Solubility of solid dispersions in distilled water Formulation Solubility of solid Dispersions Solubility of pure drug Table : Drug content of solid dispersions Table 4: Composition of fast dissolving tablets of ibuprofen Ingredients(mg/tablet) FDT1 FDT FDT FDT4 FDT5 FDT6 Solid dispersions containing 50 mg of drug. Crosscarmellose 0 10 _ 10 Crosspovidone _ Sodium starch glycolate _ Camphor Saccharin sodium starch Talc Magnesium stearate Formulation Table 5: Evaluation of pre-compression parameters Bulk density(g/ml) Tapped density(g/ml) Haussner s ratio Compressibility Index (%) Angle of repose(θ) F º96 F º1 F º61 F º10 F º4 F º86 Formulation S S S Formulation Drug content S1 95.% S 97.5% Table 6.Evaluation of post-compression parameters Hardness test(kg/m ) S 9.% Weigh variation Friability (%) Disintegratio n test(sec) Wetting time(sec) Drug content (%) F1.5 Complies F Complies F.8 Complies F4.6 Complies F5.8 Complies F6. Complies Available online: May Issue 517

10 Table 7: Cumulative Percentage Drug Release Data for Prepared FDT'S TIME(min) FTD1 FTD FTD FTD4 FTD5 FTD Fig 5: Cumulative Percentage Drug Release FTD1 FTD FTD FTD4 FTD5 FTD6 CONCLUSION The present investigations showed that, fast dissolving tablets of Ibuprofen can be successfully prepared by using solid dispersions of the drug with urea and then blending with suitable proportions of superdisintegrants such as; Crosscarmellose sodium (CC) and sodium starch glycolate (SSG). After direct compression, In view of the data of all forms of evaluation studies, the optimized formulation was found to be FDT6. REFERENCES 1. Tejvirkaur, Bhawandeep gill, Sandeepkumar, Mouth dissolving tablets: a novel approach to drug delivery; International Journal of Current Pharmaceutical Research, Vol, Issue 1, 011,( ).. Nyol sandeep, Dr. M.M. Gupta, Immediate drug release dosage form: A review; journal of drug delivery & therapeutics; 01, (), ( ).. Mouth Dissolving Tablets; Review; International journal of advances in pharmacy, biology and chemistry,vol. 1(4), oct- dec, 01 ( ). Available online: May Issue 518

11 4. Syed Shariff Miyan, Mohammed Khaleel, Vazir Ashfaq Ahamed and H. Mohammed Yakhoob; Design and development of fast dissolving tablets of gliclazide by solid dispersions technique; IJPCBS (), 01, (4-50). 5. Formulation and Evaluation of Solid Dispersion of Aceclofenac Mohammed Gulzar Ahmed *, Kiran Kumar GB, Satish Kumar BP and Harish AR Dept of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, BG Nagar, India. 6. Manavalan R and Ramaswamy L. Physiccal Pharmaceutics 1st Edn., Vighnesh Publishers. (41). 7. Subramanyan CVS. Text book of Physical Pharmaceutics. 1st Edn., Published by Vallabh Prakash.(). 8. Alfred Martin. Text book of Physical Pharmacy 4th Edn., B.I Wavesly Pvt Lts.(44). 9. Bhagwati ST, Hiremath SN, Srinivas SA. Comparative Evaluation of disintegrants by formulating Cefixime dispersible tablets. Indian Journal of Pharmaceutical Education ; 005 Oct-Dec., 9(4); (194). 10. Kuchekar BS, Badhan AC, Mahajan HS. Mouth Dissolving tablets of Salbutamol Sulphate. A Novel drug delivery system. Indian Drugs 004 Oct, 41(10);(59-594). 11. Sudhir Bhardwaj, Vinay Jain, R.C. Jat, Ashish Mangal, Suman Jain.Formulation and evaluation of fast dissolving tablet of aceclofenac. International Journal of Drug Delivery ; 010; (9-97). Available online: May Issue 519