Candesartan cilexetil

Candesartan cilexetil is a prodrug of candesartan – a compound that inhibits binding of angiotensin II to the AT1 – receptor.  It is mainly used in the treatment of hypertension. In the present work attempts were mase to prepare fast dissolving tablets of candesartan cilexetil by sublimation technique. The prepared formulations were evaluated for pre-compressional and post-compressional parameters. The compatibility of drug with other ingredients was checked by FTIR studies, these results revealed that there was no interaction between dug and other excipients. The values of pre-compressional parameters were within prescribed limits and indicated good free flowing properties. In all the formulations the hardness test indicates good mechanical strength. Friability of all formulations was less than 1. Drug content was found to be high (≥ 100.27%) and uniform in all the formulations. The tablet thickness was found to be 3.14 – 3.47. The weight variation results revealed that average percentage deviation was less then ± 7.5 %, which provides good uniformity in all formulations. The disintegration time of the tablets decreased significantly with increase in the concentration of subliming agent. The formulations CSC3, CSM3, CSA3, and CSU3 50 % of drug released in 1.38, 2.55, 4.00 and 3.57 min, and 90 % of drug released in 3.39, 6.04, 7.50 and 7.18 min. The formulation CS (control) released 42.16 % in 60 min. Stability study carried out as per ICH guidelines for three months and results revealed that upon storage disintegration time of tablets decreased significantly (p<0.05). The results concluded that by adopting a systemic formulation approach, an optimum point could be reached in the shortest time with minimum efforts. Sublimation technique would be an effective alternative approach compared with the use of more expensive adjuvants in the formulations of fast dissolving tablets.

The aim of the present study is to develop and evaluate floating microspheres containing candesartan cilexetil in order to achieve extended release of drug and thereby to enhance the patient compliance. Floating microspheres were prepared by using solvent evaporation method. The microspheres were formulated using different polymers like ethyl cellulose, HPMC K4M and eudragit RSPO 100 in different concentrations and combinations. The prepared floating microspheres were characterized for their percentage yield (95.44 - 98.52%), drug entrapment efficiencies (71.52 - 97.87 %) and percentage buoyancy (93.45 - 98.66%). The FTIR and DSC studies revealed absence of interactions between drug and selected polymers. In vitro release studies were performed in 0.1 N HCl which showed a drug release of 97.62 % at 24 hour in case of formulation (F7). Fitting the in vitro drug release data to Korsmeyer equation indicated that Fickian diffusion is the mechanism of drug release.

A simple, accurate and sensitive RP-HPLC method was developed and validated for the determination of candesartan cilexetil and hydrochlorothiazide in tablet dosage form. The separation of the two drugs was achieved on a Reprospher 100 –C l 8 column (250 x 4.6 mm, 5 µm particle size) with UV detection at 260 nm. The mobile phase consists of two solution, solution (1) orthophosphoric acid (pH 2.2) and the solution (2) which is acetonitrile and purified water in the ratio 55: 45 v/v, respectively. The method was validated in terms of linearity, accuracy, precision, specificity, limit of detection, limit of quantitation and robustness. Linearity was observed in the concentration range 10-70µg/ml for hydrochlorothiazide and 12.8 -89.6µg/ml for candesartan cilexetil. The limit of quantitation was found to be 8.58 and 4.6 µg/ml for hydrochlorothiazide and candesartan cilexetil, respectively whereas the limit of detection, was found to be 2.8 and 1.5 µg /ml for hydrochlorothiazide and candesartan cilexetil, respectively. The % recovery range of candesartan cilexetil was 97.84-101.62% and 100.9-101.53% for hydrochlorothiazide. Variation in HPLC conditions (flow rate, column temperature, mobile phase composition, and wavelength) were used to evaluate the robustness of the method. The method proved to be robust and still produces good results.