Study of the Complexation Behaviour of Fexofenadine with ß-Cyclodextrin.

Fexofenadine is a selective histamine H(1) receptor antagonist, used for relief of the symptoms of allergy. However its aqueous solubility is very poor. Solid inclusion complexes of fexofenadine and ß-cyclodextrin were prepared at the molar ratios of 1:1 and 1:2 by kneading, and coprecipitation methods to improve its solubility. Characterization of the complexes was performed using infrared spectroscopy, X-ray diffractometry, and in vitro dissolution studies. Fexofenadine was found to exhibit interaction with ß-cyclodextrin both in solid and liquid state. Phase solubility studies indicated that fexofenadine forms a stable complex with ß-cyclodextrin. Both IR spectroscopy and X-ray diffractometry studies indicated interaction of fexofenadine with ß-cyclodextrin. Kneading method at 1:1 and co-precipitation method at 1:1 and 1:2 molar ratios showed significant interaction. In vitro dissolution studies confirmed the same results.

Synthesis and pharmacological investigation of 3-(substituted 1-phenylethanone)-4-(substituted phenyl)-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylates.

Fifteen new ethyl 6-methyl-2-methoxy-3-(substituted 1-phenylethanone)-4-(substituted phenyl)-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylates (6a-o) have been synthesized in a two step reaction. In first step ethyl acetoacetate, s-methylisourea and appropriate benzaldehydes reacted in a single step reaction to obtain ethyl 6-methyl-2-methoxy-4-(substituted phenyl)-1, 4-dihydropyrimidine-5-carboxylates (4a-e). Second step involves synthesis of reaction between substituted phenacyl bromides and 1-4-dihydropyrimidine-5-carboxylates (6a-o). Their structures are confirmed by IR, (1)H NMR, mass and elemental analyses. The compounds were tested for antihypertensive activity by non-invasive tail-cuff, and evaluated by carotid artery cannulation method for determining the diastolic blood pressure. Hypertension was induced by DOCA-salt. Anti-inflammatory activity was carried out by carrageenan induced rat-paw oedema method. Test compounds 6b, 6c, 6e, 6f, 6j, 6h, 6k, 6l, 6m, 6n and 6o exerted comparative antihypertensive activity at 10 mg/kg dose level compared to nifedipine. Compounds 6j, 6m and 6o showed excellent results on evaluation by direct method. Test compounds 6a-6h, 6l, 6m, 6n and 6o exerted moderate to comparative anti-inflammatory activity at the 100 mg/kg dose level compared to indomethacin. Their further investigation for analgesic activity and acute ulcerogenesis was carried out, compounds 6m, 6f, 6k, 6o showed excellent to good analgesic activity and low ulcerogenic activity.

Derivative and Q-analysis Spectrophotometric Methods for Estimation of Hydrochlorothiazide and Olmesartan Medoxomil in Tablets.

Two methods for simultaneous estimation of hydrochlorothiazide and olmesartan medoxomil in combined tablet dosage form have been developed. The first method is the application of Q-analysis method (absorbance ratio), which involves the formation of Q-absorbance equation at 264 nm (isobestic point) and at 271 nm, the maximum absorption of hydrochlorothiazide. The linearity ranges for hydrochlorothiazide and olmesartan medoxomil were 2.5-22.5 mug/ml and 4-36 mug/ml, respectively. The second method is based on the derivative spectrophotometric method at zero crossing wavelengths. The linearity ranges for hydrochlorothiazide and olmesartan medoxomil were 2.5-20 mug/ml and 4-32 mug/ml, respectively. The accuracy of the methods were assessed by recovery studies and was found to be 100.45% +/-0.4215 and 100.24% +/-0.3783 for absorbance ratio method and 99.39% +/-0.221 and 99.72% +/-0.11 for first derivative method, for hydrochlorothiazide and olmesartan medoxomil, respectively. These methods are simple, accurate and rapid, those require no preliminary separation and can therefore be used for routine analysis of both drugs in quality control laboratories.