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Research Article ISSN: 0974-6943 V.Felix Joe et al. / Journal of Pharmacy Research 2011,4(2),507-508 Available online through http://jprsolutions.info Formulation and evaluation of Pseudoephedrine hydrochloride and Loratadine extended release tablet. V. Felix Joe *1, Prasanth V. V2, B. A. Viswanath 1, Rinku Mathappan2, Kamalakkannan Vairappan3, Sam .T.Mathew4 Department of Pharmaceutics, Aditya Bangalore Institute for Pharmacy Education and Research, Bangalore – 560064, India 2 Department of Pharmaceutics, Gautham College of Pharmacy, Bangalore 560032, India 3 Caplin Point Laboratories Limited, Puducherry - 605 502, India 4 Accenture Pharmaceutical services, Bangalore, 560072, India *1 Received on: 10-09-2010; Revised on: 17-10-2010; Accepted on:13-01-2011 ABSTRACT The present study was aimed to develop extended release tablets of pseudophedrine hydrochloride and loratadine using hydroxy propyl methyl cellulose and sodium carboxymethylcellulose in different proportions a matrix material in core tablet and loratadine is used as immediate release for this a film coating formula was developed, so as to provide immediate release from the zone of coating. The results of the dissolution study indicated the formulations FC – VI and FC – VII showed maximum drug release up to 12 hr, the release of the drug was found to be dependent on the relative proportions of hydroxypropylmethylcellulose and sodiumcarboxymethylcellulose used in core tablet. Mathematical treatment of the in vitro drug release data suggests that, all the formulations best fitted into first order release kinetics. Drug release from the matrix occurred by combination of two mechanisms, diffusion of drug from tablet matrix and erosion of tablet surface. Key words:Pseudoephedrine hydrochloride, loratadine, extended release and film coating INTRODUCTION Pseudoephedrine Hydrochloride a sympathomimetic drug effective for treating nasal congestion. Loratadine, a non-sedating Antihistaminic agent is also known to be useful as an anti-allergy agent for the treatment of seasonal allergic rhinitis symptoms such as sneezing and itching. Therefore an oral dosage composition containing both loratadine and pseudoephedrine is used for treating patients showing the sign and symptoms associated with upper respiratory diseases and allergic rhinitis [1, 2]. Biological half-life of Pseudoephedrine Hcl is only about 6.3hours, while loratadine which combines with plasma proteins after being absorbed through the gastrointestinal tract has a much longer biological half-life of 12-15hrs. Further loratadine has poor water solubility and exhibits a very low dissolution rate. Therefore a conventional formulation prepared by simply mixing loratadine and pseudophedrine is not capable of maintain therapeutically effective blood concentrations of both ingredients at the same time for a prescribed period. A film coated tablet comprising an extended release matrix core containing Pseudoephedrine Hydrochloride and a hydrophilic gel, a coating layer containing loratadine being formed when this formulation is ingested, loratadine having a longer biological half-life is released from the coating layer before the dissolution of Pseudoephedrine Hydrochloride having a shorter biological half-life from the extended release matrix core [1, 2]. The selection of release regarding excipients is necessary to achieve a constant in vivo input rate of the drug. The matrix tablets composed of drug and the release retarding material (polymer) offers the simplest approach in designing an extended release system [3]. Number of studies shows the use of hydrophilic matrices to formulate the controlled release dosage forms of different drugs. Because of their simplicity and cost effectiveness, matrix tablets are widely used for oral controlled release dosage forms. Hydrophilic polymers from a gel like structure around the tablet core, which controls the drug release. The Hydrophilic polymer hydroxy propyl methylcellulose and sodium carboxymethylcellulose was selected in the present study is a pH- independent material, which has been widely used to prepare extended release dosage forms [4]. *Corresponding author. V.Felix Joe Lecturer Department of Pharmaceutics Aditya Bangalore Institute of Pharmacy Education and Research Bangalore – 560064, India Hence in the present work, an attempt has been made to develop extendedrelease matrix tablets of Pseudoephedrine Hydrochloride and loratadine and to study the in vivo release characteristics and kinetics of the prepared formulations. MATERIALS AND METHODS Pseudoephedrine Hcl, Loratadine, as gift sample were obtained from Medo Pharm, Chennai, India. Hydroxy propyl methylcellulose, Carboxy methylcellulose were obtained as gift samples from Colorcon Asia Pvt.Ltd (Goa, India). Dicalcium Phosphate and polyvinylpyrrolidine (pvp-k30). Materials and excipients used in preparing tablets were of IP grade. All the other ingredients used throughout the study were of Analytical grade. Preparation of core matrix tablets: Different tablet formulations (Batch size of 300 tablets) were prepared by wet granulation technique i.e. F-I to F-VII (Table 1). Accurately weighed quantities of pre-sieved drug, Pseudoephedrine Hydrochloride, Hydroxy propyl methyl cellulose, sodium carboxy methyl cellulose, Dicalcium phosphate and Polyethylene glycol 6000 were mixed uniformly and wetted with solution of PVP in IPA as granulating fluid, the cohesive mass this obtained was screened through a sieve NO:12. The granules were dried at 40°c for 15 minutes. The coarse granules so obtained were once again screened using the same sieve. Stearic Acid, Microcrystalline cellulose and silicon dioxide were finally added as antifrictional agents to the uniform sized granules and the granules were compressed (11.11mm diameter, biconvex punches) in a rotary tablet machine [3]. Each tablet contained 400mg of Pseudoephedrine hydrochloride and other excipients as listed in Table.1 Evaluation of Granules: Both loose bulk density (LBD) and tapped bulk density (TBD) were determined. A quantity of 2g of granules from each formulation. Previously lightly shaken to break any agglomerates, was introduced a 10ml measuring cylinder. After the initial volume was observed, the cylinder was allowed to fall under its own weight onto a hard surface from the height of 2.5cm at 2sec intervals. After 300 taps, the tapped volume of packing was noted. LBD and TBD were calculated using the formulae; LBD = weight of the powder / volume of the packing. TBD = weight of the powder / tapped volume of the packing. The compressibility index of the granules was determined by Carr’s compressibility index, Carr’s index (%) = [(TBD – LBD) x 100] / TBD. The angle of repose of granules was determined by the funnel method. The accurately weighed Journal of Pharmacy Research Vol.4.Issue 2. February 2011 507-508 V.Felix Joe et al. / Journal of Pharmacy Research 2011,4(2),507-508 granules were taken in a funnel, which was maintained at 4 inches from the surface. The granules were allowed to flow through the funnel freely onto the surface. The diameter of the powder cone was measured and angle of repose was calculated using the equation tanθ = h/r, θ = tan-1 h/r, where θ is the angle of repose, ‘h’ is the height in cm of the powder cone and r the radius in cm of the powder cone. Moisture content of granules was determined using Karl Fisher instrument [3] Evaluation of matrix tablets: Hardness test: For the determination of the hardness, Pfizer hardness tester was used. For each formulation 10 tablets were determined [5, 6]. Weight variation test: Twenty tablets were randomly selected and weighed to determine the average weight and were compared with individual tablet weight. The percentage weight variation was calculated [5, 6]. Thickness and diameter test: The thickness and diameter was determined for 10 tablets with the help of a digital vernier caliper. Friability test: Weighed amount of 20 dedusted tablets were subjected to rotating drum of friability test apparatus. The drum was rotated at a speed of 25 rpm for 4 minutes and reweighed the tablets [5, 6]. Drug content: Drug content of the matrix tablets was determined by weighing and finely grinding 10 tablets of each batch. Aliquot of this powder equivalent to 25mg of Pseudoephedrine Hydrochloride and dilute to 100ml with water to get a solution of 25mcg/ml. To 5ml each of standard and sample solutions added 1ml of sodium carbonate solution and 2ml of sodium Meta periodate solution mix. Allow standing for 10 minutes. Add 20ml of n-hexane and shake for 30 seconds. Measure the absorbance of both standard and sample solutions at the maximum at about 242nm using uv/vis spectrophotometer. In vitro release studies The in vitro release rate studies were carried out in USP dissolution test apparatus Type I in distilled water from 3-12 hr. rotation speed of 50 rpm at temperature of 37 ± 0.5° the dissolution medium of 900ml was maintained throughout the experiment. At predetermined time intervals, 10ml of sample was with drawn and replaced with the same volume fresh dissolution medium. The samples withdrawn were filtered through 0.45µ membrance filters, and drug content in each sample was analyzed after suitable dilution by uv/vis spectrophotometer at 242nm. All dissolution studies were carried out in duplicate and repeated at least thrice [3]. Preparation of coating solution With the objective to develop Pseudoephedrine (ER) and Loratadine (IR) combination a coating formula was developed so as to provide immediate release of loratadine from the zone of coating. Loratadine was deposited in the form of a thin and uniform film. Loratadine is dissolved in IPA coating solution is prepared by the mixture of titanium dioxide, HPMC, castor oil and methylene chloride. To the above mixture drug solution is added and stirred well. Tablets are transferred to a coating pan and the coating solution sprayed on the core tablet. During coating, the temperature is maintained at 40°c. The formula for coating solution is given in Table II. The coated tablets were evaluated for drug dissolution, assay and other parameters. Evaluation of coated tablets Drug content of the coated tablets was determined by weighing and finely grinding 10 tablets weigh accurately about 10mg loratadine equivalent sample powder in 20ml volumetric flask. Add 10ml methanol and shake for 10 minutes make up with mobile phase. Filter through 0.45 µ filter paper and inject the filtrate by high performance liquid chromatography and the content was compared from a calibration curve prepared with standard loratadine in the same medium. Table 1. Tablet formulations with combined matrix material Sl.No Ingredients (mg / tablet) F-I F-II F-III F-IV F-V F-VI F-VII 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Pseudoephedine Hydrochloride Dicalcium Phosphate Hydroxy Propyl Methyl Cellulose Poly Vinyl Pyrolidone Silicon dioxide Magnesium Sterate Stearic Acid Talc Isopropyl Alcohol Methylene Chloride Microcrystalline Cellulose Ethyl Cellulose Sodium Carboxymethyl Cellulose Polyethylene Glycol 6000 120 200 25 6 10 3 3 3 Q.S Q.S - 120 120 10 6 3 6 Q.S Q.S 60 60 - 120 123 26 6.6 6.6 6.6 Q.S Q.S 50 50 - 120 147 20 13 3 13 Q.S Q.S 30 147 16 - 120 90 80 40 8 13 Q.S Q.S 13 100 8 120 100 80 90 8 13 Q.S Q.S 13 100 8 120 180 40 6.6 6.6 6.6 Q.S Q.S 30 60 - Table 2. Film Coating Solution Sl.No Ingredients Qty / Batch (gm) 1 2 3 4 5 6 Loratadine Hydroxy Propyl Methyl Cellulose Titanium dioxide Castor Oil Isopropyl Alcohol Methylene Chloride 8.25 10.200 9.800 0.006 0.120 0.300 RESULTS AND DISCUSSION Formulation of granules is the key factor in the production of tablet dosage from involving extended release of drug from matrix type particle. Physical parameters such as area, hardness, surface characteristics and size can significantly affect the rate of dissolution of drugs contained in a complex system. The selection of wet granulation technique for matrix tablet preparation was based on previously reported study which suggested that wet granulation results in harder tablets with lower matrix porosity that give very slow release rates when compared to direct compression. The granules of different formulations were evaluated for LBD, TBD, compressibility index, angle of repose and moisture content. The LBD and TBD of granules ranged from 0.19 ± 0.6g/ml and 0.26 g/ml respectively. Compressibility index values up to 15% result in good to excellent flow properties, but readings above 25% indicates poor flowability. Angle of repose values form 27.53 ± 0.12° to 38.32 ± 0.25°. Generally values of angle of repose are rarely less than 20° and values up to 40° indicate reasonable flow properties. All these results indicate that the formulated granules possessed satisfactory flow properties and compressibility. The moisture content of all the formulations was found to be satisfactory. The results of hardness and friability of the prepared matrix tablets ranged from 5.5 ± 0.22 to 8 ± 0.12 kg/cm2. All the batches of fabricated tablets were of good quality with regard to hardness, friability and drug content. The results of thickness and diameter of tablets ranged from 4.0 ± 0.05 to 5.4 ± 0.02 and 10.4 ± 0.3 to 11.3 ± 0.2 mm, respectively. Thus all formulations showed uniform variation results of the matrix tables ranged from 395 ± 1 to 406 ± 1 mg. For weight variation test, the pharmacopocial limit for the percentage deviation for tablets of more than 250mg is ± 5%. The average percentage deviation of all tablet formulations was found to be within the above limit in compliance with official standards. Defined bulk weight per tablet is 400mg-containing 120mg of Pseudoephedine Hydrochloride; F-I to F-VII represents the various formulations of Pseudoephedine Hydrochloride. In which F-VI Dissolution profile was satisfactory and complies with the limit of 12hr. By using this F-VI formula a stability batch F-VII was taken and their dissolution was also satisfactory. REFERENCES 1. 2. 3. 4. 5. 6. Kim HS, Park YJ, HB Jo, Pharmaceutical capsule compositions containing loratadine and psuedoephedrine - US Patent 6, 2001, 251,427. Irwin J, Shati T, Shrish A. Pseudoephedine Hydrochloride extended release tablets - United States Pant 5,1999, 895,663, Keny R V, Mankame SA, Lourenco CF. Formulation and Evaluation of Once Daily Minocycline Hydrochloride Extended Release Matrix Tablets. Indian J Pharm Sci 2009, 71(3): 295–302 Ganesh S, Radhakrishnan M, Ravi M, Prasannakumar B, Kalyani J. In vitro Evaluation of the Effect of Combination of Hydrophilic and Hydrophobic Polymers on Controlled Release Zidovudine Matrix Tablets. Indian J Pharm Sci 2008, 70(4): 461–465 Pandey S, Viral D, Manish G. Formulation and Evaluation of Taste Masked Fast Disintegrating Tablets of Lisinopril. International Journal of PharmTech Research 2010, 2(2): 1639-1643 The E-Tongue in pharmaceutical industry, AAPS exhibition: Booyh 442. Source of support: Nil, Conflict of interest: None Declared Journal of Pharmacy Research Vol.4.Issue 2. February 2011 507-508