Preparation and Evaluation of Orodispersible Tablets of Pheniramine Maleate by Effervescent Method

Indian Journal of Pharmaceutical Sciences 151 March April 2009 accurate analytical HPLC method for the simultaneous estimation of these drugs without their prior separation. The method gives good resolution between both the compounds with a short analysis time (<10 min). The method was validated and found to be simple, sensitive, accurate and precise. Percentage of recovery shows that the method is free from interference of the excipients used in the formulation. Therefore, the proposed method can be used for routine analysis of ramipril and telmisartan in their combined dosage form.

accurate analytical HPLC method for the simultaneous estimation of these drugs without their prior separation.The method gives good resolution between both the compounds with a short analysis time (<10 min).The method was validated and found to be simple, sensitive, accurate and precise.Percentage of recovery shows that the method is free from interference of the excipients used in the formulation.Therefore, the proposed method can be used for routine analysis of ramipril and telmisartan in their combined dosage form.Many patients express difficulty in swallowing tablets and hard gelatin capsules, tending to non-compliance and ineffective therapy [1] .Recent advances in novel drug devliery systems (NDDS) aim to enhance safety and efficacy of drug molecules by formulating a convenient dosage form for administration and to achieve better patient compliance.One such approach is orodispersible tablet [1][2][3][4] .Advantages of this drug delivery system include administration without water, accuracy of dosage, easy portability, alternative to liquid dosage forms, ideal for pediatric and geriatric patients and rapid onset of action.Pheniramine maleate is a member of alkylamine class of H 1 receptor antagonists.It is an antihistamine used in the treatment of allergic conditions including urticaria and angioedema [5] .Orodispersible tablets of pheninamine maleate were prepared by effervescent method [6] according to the formulae given in Table 1.Sodium bicarbonate and tartaric acid were preheated at a temperature of 80 o 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 shifting through sieve No. 44 were thoroughly mixed in a tumbling cylindrical blender (fabricated in our laboratory).The blend thus obtained was directly compressed using 8 mm round flat beveled edge punches to get tablets of 150 mg weight on 10-station rotary tablet machine (Clit, Ahmedabad).A batch of 60 tablets was prepared for all the designed formulations.
Twenty tablets were selected at random and weighted 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 a Monsanto Hardness Tester and a Roche Friabilator, respectively.For content uniformity test, ten tablets were weighed and powdered.The powder equivalent to 12.5 mg of pheniramine maleate was extracted into methanol and liquid was filtered.The pheninamine maleate content was determined by measuring the absorbance at 265 nm after appropriate dilution with methanol.
The drug content was calculated 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 ± 0.5° and the time required for complete dispersion was determined [9] .IR spectra of pheniramine maleate and its formulations were obtained by KBr pellet method using Perkin-Elmer FTIR series (model-1615) spectrophotometer in order to rule out drug-carrier interactions.
In vitro dissolution of pheniramine maleate orodispersible tables was studied in USP XXIII type-II dissolution apparatus (Electrolab, Model-TDT 06N) employing a paddle stirrer at 50 rpm using 900 ml of pH 6.8 phosphate buffer at 37±0.5 o as dissolution medium [10] .Aliquots of dissolution medium were withdrawn at specified intervals of time and analyzed for drug content by measuring the absorbance at 265 nm.The volume withdrawn at each time interval was replaced with fresh quantity of dissolution medium.Cumulative percent of pheniramine maleate released was calculated and plotted against time.
Short term stability studies on the promising formulation ECP 4 were carried out by storing the tablets in an amber coloured rubber stoppered vial at 40±2 o /75±5% RH over a 3 mo period.At intervals of one month, the tablets were visually examined for any physical changes, changes in drug content and in vitro dispersion time.
Orodispersible tablets of pheniramine maleate were prepared by effervescent method using pregelatinized starch (PGS), sodium starch glycolate (SSG), croscarmellose sodium (CC) and crospovidone (CP) as super-disintegrants while microcrystalline cellulose (MCC) and directly compressible mannitol (Pearlitol SD200) were used as diluent and sweetening agent respectively.The slight bitter taste of the drug has been masked by using 4% w/w of aspartame and 2% w/w of flavouring agent (spray dried pineapple flavour, Trusil).A total of 12 formulations and a control formulation E o (without super-disintegrants) were designed.
As the material was free flowering (angle of repose values < 30 o 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 97.52 to 101.56%, which is within acceptable limits.Hardness of the tablets was found to be 2.57 to 2.93 kg/cm 2 .Friability below 1.2% was an indication of good mechanical resistance of the  [11] , t 50% and t 70% are shown in IR spectroscopic studies indicated that the drug is compatible with all the excipients.The IR spectrum of ECP 4 showed all the characteristic peaks of pheniramine maleate pure drug, thus confirming that no interaction of drug occurred with the components of the formulation.Short-term stability studies of the above formulation indicated that there were no significant changes in drug content and in vitro dispersion time at the end of a 3 mo period (P < 0.05).

TABLE 1 : SUMMARY OF VALIDATION PARAMETERS
a RSD indicates relative standard deviation; RAM is ramipril and TEL is telmisartan

TABLE 2 : SYSTEM SUITABILITY TEST PARAMETERS FOR RAMIPRIL AND TELMISARTAN BY THE PROPOSED METHOD
*mean of six observationscompliance by effervescent method.

TABLE 1 : COMPOSITION OF DIFFERENT BATCHES OF ORODISPERSIBLE TABLETS OF PHENIRAMINE MALEATE Ingredients Formulation Code (mg/tablet) Eo EP 2 EP 4 EP 6 EP 8 ES 2 ES 4 ES 6 ES 8 ECC 2 ECC 4 ECP 2 ECP 4
Formulations EC 4 , ECC 2 and ECP 4 were selected as the best and used in further studies.

TABLE 2 : EVALUATION OF ORODISPERSIBLE TABLETS
Average of three determinations.E 0 = Control formulation without super disintegrant, EP= Formulations containing pregelatinized starch as superdisintegrant, ES=Formulations containing sodium starch glycolate as superdisintegrant, ECC= Formulations containing croscarmellose sodium as superdisintegrant.ECP= Formulations containing crospovidone as superdisintegrant.CP was found to be overall best promising formulation and has shown an in vitro dispersion time of 19 s, when compared to ES 4 , ECC 2 and control (E o ) formulations which show 35, 39 and 59 s values, respectively for the above parameter (Table2).The performance of the above formulations based on in vitro dispersion time in decreasing order is as follows: ECP 4 >ES 4 >ECC 2 >E 0 . *

TABLE 3 : iN Vitro DISSOLUTION PARAMETERS IN PH 6.8 PHOSPHATE BUFFER
conventional commercial formulation, t 50% = time for 50% drug dissolution, t 70% = time for 70% drug dissolution, DE 4 min = dissolution efficiency in 4 min, D 4 = percent drug released in 4 min. CF=