Fast Dissolving Tablets of Fexofenadine HCl by Effervescent Method

Indian Journal of Pharmaceutical Sciences 116 March April 2009 of extracts of C. trifoliata has been evaluated in vitro against gram positive and negative bacteria (Table 1) that are known to cause infections in humans and plants. As presented in Table 1 the inhibitory effect of the extracts of C. trifoliata was increased by the concentration of extracts. Although both the extracts showed significant inhibitory effect against Staphylococcus aureus, Bacillus subtilis, Enterobacter aerogenes and Escherichia coli at both concentrations (200 μg/ml and 800 μg/ml) they did not show any activity against Erwinia and Acinetobacter.

of extracts of C. trifoliata has been evaluated in vitro against gram positive and negative bacteria (Table 1) that are known to cause infections in humans and plants.As presented in Table 1 the inhibitory effect of the extracts of C. trifoliata was increased by the concentration of extracts.Although both the extracts showed significant inhibitory effect against Staphylococcus aureus, Bacillus subtilis, Enterobacter aerogenes and Escherichia coli at both concentrations (200 µg/ml and 800 µg/ml) they did not show any activity against Erwinia and Acinetobacter.
In conclusion, the aqueous and alcoholic extracts of C. trifoliata leaf possess significant inhibitory effect against the tested pathogens.The results obtained were comparable with those of standard drug ciprofloxacin.However both the extracts did not show any inhibitory effect on plant pathogens.The results of the study support the folklore claim of this plant.Many patients find it difficult to swallow tablets and hard gelatin capsules and thus do not comply with prescription, which results in high incidence of non-compliance and ineffective therapy.Recent advances in novel drug delivery systems (NDDS) aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance; one such approach is fast dissolving tablets [1][2][3][4] .Fexofenadine HCl (FXD), is a non-sedating antihistamine used in the symptomatic relief of allergic conditions including seasonal allergic rhinitis and urticaria [5] .The concept of formulating fast dissolving of tablets containing fexofenadine HCl offers a suitable and practical approach in serving desired objective of faster dissolving and dissolution characteristics with increased bioavailability.
Directly compressible mannitol (Pearlitol SD 200) and sodium stearyl fumarate (SSF) were generous gifts from Strides Acrolabs, Bangalore, India.All the other chemicals used were of analytical reagent grade.
For the preparation of fast dissolving tablets, effervescent method [6] was used.All the ingredients (except SSF and purified talc) were accurately weighed and sifted through # 44 mesh separately, sodium bicarbonate and anhydrous citric acid were pre-heated at a temperature of 80º to remove absorbed/residual moisture and were thoroughly mixed in a mortar to get a uniform powder and then added to other ingredients.The ingredients after sifting through sieve No. 44 were thoroughly mixed in a tumbling cylindrical blender (fabricated in our laboratory).The blend thus obtained was directly compressed into tablets of 150 mg weight on a 10-station rotary machine (Clit, Ahmedabad, India) using 8 mm round flat punches.The tablets were prepared according to the formulae shown in Table 1.
Twenty tablets were selected at random and weighed individually.The individual weights were compared with the average weight for determination of weight variation [7] .Hardness and friability of the tablets were determined by using Monsanto hardness tester and Roche friabilator, respectively.For determining the content uniformity, ten tablets were weighed and powdered.The powder equivalent to 30 mg of FXD was extracted into methanol and liquid was filtered (Whatman No. 1 filter paper).The FXD content in the filtrate was determined by measuring the absorbance at 259 nm after appropriate dilution with methanol.
The drug content was determined using the standard calibration curve.The mean percent drug content was calculated as an average of three determinations [8] .For determination of in vitro dispersion time, one tablet was placed in a beaker containing 10 ml of pH 6.8 phosphate buffer at 37±0.5º and the time required for complete dispersion was determined [9] .IR spectra of FXD and its formulations were obtained by potassium bromide pellet method using Perkin-Elmer FTIR series (Model 1615) spectrophotometer in order to rule out drug-carrier interactions.
In vitro dissolution of FXD fast dissolving tablets was studied in USP XXIII type-2 dissolution apparatus (Electrolab, Model-TDT 06N) employing a paddle stirrer at 50 rpm using 900 ml of pH 6.8 phosphate buffer at 37±0.5º as dissolution medium.One tablet was used in each test.Aliquots of dissolution medium (5 ml) were withdrawn at specific intervals of time and analyzed for drug content by measuring the absorbance at 259 nm.The volume withdrawn at each time interval was replaced with fresh quantity of dissolution medium.Cumulative percent of FXD released was calculated and plotted against time.
Short-term stability studies on the promising formulations (ECP 3 , ECCS 3 and ESSG 3 ) were carried out by storing the tablets in amber coloured glass vial with rubber stopper at 40º/75% RH over a 3 mo period (as per ICH guidelines).At an interval of 1 mo, the tablets were visually examined for any physical changes, changes in drug content and in vitro dispersion time.
Fast dissolving tablets of FXD were prepared by effervescent method, as this method has the advantage of taste masking.Further, aspartame 5% and 1% flavour was used in the formulations to enhance the mouth feel, employing CP, CCS and SSG as super-disintegrants along with mixtures of sodium bicarbonate and anhydrous citric acid in different ratios.Directly compressible mannitol (Pearlitol SD 200) was used as a diluent to enhance mouth feel [9] .A total of nine formulations and a control formulation EC 0 (without super-disintegrant) were designed [10] .
As the blends were free flowing (angle of repose <30º, and Carr's index <15%) tablets obtained were of uniform weight (due to uniform die fill), with acceptable variation as per IP specifications i.e., below 7.5%.Drug content was found to be in the range of 95 to 101%, which is within acceptable limits.Hardness of the tablets was found to be 2.5 to 2.8 kg/ cm².Friability below 1% was an indication of good mechanical resistance of the tablets.Among all the designed formulations, three formulations, viz., ECP 3 , ECCS 3 and ESSG 3 were found to be promising and displayed an in vitro dispersion time ranging from 19 to 26 s, which facilitates their faster dispersion in the mouth.
Overall, the formulation ECP 3 containing 8% w/w of crospovidone along with mixture of sodium bicarbonate 24% w/w and anhydrous citric acid 18% w/w was found to be promising and has shown an in vitro dispersion time of 20 s when compared to control formulation (EC 0 ) which shows 498 s value for in vitro dispersion (Table 2).
In vitro dissolution studies on the promising formulations (ECP 3 , ECCS 3 and ESSG 3 ), the control (EC 0 ) and commercial conventional formulations (CCF) were carried out in pH 6.8 phosphate buffer, and the various dissolution parameter values viz., percent drug dissolved in 5 min, 10 min and 15 min (D 5 , D 10 and D 15 ), dissolution efficiency at 10 min (DE 10 min ) [11] , t 50% , t 70% and t 90% , the dissolution profiles depicted in fig. 1.This data reveals that overall, the IR spectroscopic studies indicated that the drug is compatible with all the excipients.The IR spectrum of ECP 3 showed all the characteristic peaks of FXD pure drug, thus confirming that no interaction of drug occurred with the components of the formulation.Short-term stability studies of the above formulations indicated that there are no significant changes in drug content and in vitro dispersion time at the end of 3 mo period (P<0.05).