Development, evaluation and optimization of baclofen oral floating tablet

The present investigation concerns the development of a floating matrix tablet, which after oral administration prolong the gastric residence time and increases bioavailability of drugs, which are predominantly absorbed from gastric region .With this aim, floating dosage form containing baclofen as drug, and different grades of HPMC as release retarding polymer was prepared. Sodium bicarbonate and citric acid were used as gas generating agents. Some factors were investigated concerning the effect of release retarding polymer on drug release behaviors like t50% and t90%. A 32 factorial design was applied to optimize the drug release profile. The amounts of HPMC K4M(X1) and HPMC K100M (X2) were selected as independent variables. The time required for 50% (t50%) and 90% (t90%) drug dissolution were selected as dependent variables. The results of full factorial design indicates that moderate amount of both the release retardant polymer, controlled the release behavior. It can be concluded from release kinetic models that the release followed Higuchi model, as the correlation coefficient (R2 value) was high in all the evaluated models. The release mechanism followed non-fickian diffusion as the release exponent (n-value) was >0.5 in all the optimized formulations.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Acute toxicity, brine shrimp cytotoxicity and relaxant activity of fruits of callistemon citrinus curtis

<p>Abstract</p> <p>Background</p> <p><it>Callistemon citrinus </it>Curtis belongs to family Myrtaceae that has a great medicinal importance. In our previous work, fruits of <it>Callistemon citrinus </it>were reported to have relaxant (antispasmodic) activity. The current work describes the screening of fractions of the crude methanol extract for tracing spasmolytic constituents so that it shall help us for isolation of bioactive compounds. Acute toxicity and brine shrimp cytotoxicity of crude methanol extract are also performed to standardize it.</p> <p>Methods</p> <p>The crude methanol extract was obtained by maceration with distilled water (500 ml) three times and fractionated successively with <it>n-</it>hexane, chloroform, ethyl acetate and <it>n-</it>butanol (300 ml of each solvent). Phytochemical analysis for crude methanol extract was performed. Acute toxicity studies were performed in mice. Brine shrimp cytotoxicity studies were performed to determine its cytotoxicity and standardize it. In other series of experiments, rabbits' jejunum preparations were used in screening for possible relaxant activities of various fractions. They were applied in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on spontaneous rabbits' jejunum preparations. In similar fashion, fractions were also tested on KCl (80 mM) -induced contractions. Calcium chloride curves were constructed in K-rich Tyrode's solution. The effects of various fractions were tested on calcium chloride curves at concentrations 1.0, 3.0, 5.0 and 10.0 mg/ml. Curves of verapamil used as reference drug at concentration 0.1 μM and 0.3 μM were also constructed. The curves were compared with their respective controls for possible right shift.</p> <p>Results</p> <p>Methanol extract tested strongly positive for saponins and tannins. However, it tested mild positive for presence of proteins, amino acids, carbohydrates and phenolic compounds. LD₅₀value for crude methanol extract is 476.25 ± 10.3 (470-481, n = 4) mg/ml. Similarly, EC₅₀value for brine shrimp cytotoxicity is 65.5 ± 7.28 (60.8- 69.4, n = 4) mg/ml. All the fractions relaxed the spontaneous and KCl-induced contractions. EC₅₀values (mg/ml) for effects of ethyl acetate fraction on spontaneous and KCl induced contractions are 2.62 ± 0.78 (2.15-3.0, n = 4) and 3.72 ± 0.86 (3.38-4.28, n = 4) respectively. Respective EC₅₀values (mg/ml) for <it>n-</it>butanol fraction are 3.59 ± 0.2(3.07-3.9, n = 4) for spontaneous, and 5.57 ± 0.2 (5.07-6.11, n = 4) for KCl- induced contractions. EC₅₀value for control calcium chloride curve (without extract) is -2.73 ± 0.19 (-2.6 - -2.81, n = 4) while EC₅₀for curves treated with 5.0 mg/ml of chloroform is -2.22 ± 0.02 (-2.16 - -2.3, n = 4). EC₅₀value for ethyl acetate treated (1.0 mg/ml) tissues is -1.95 ± 0.10 (-1.88 - -2.0, n = 4) <it>vs</it>. control EC₅₀= -2.71 ± 0.08 (-2.66 - -2.76, n = 4). All the fractions, except <it>n-</it>hexane, showed a right shift like that of verapamil (EC₅₀= -1.72 ± 0.15 (-1.62 - -1.8, n = 4) vs. Control EC₅₀= -2.41 ± 0.06 (-2.38 - - 2.44, n = 4), a standard drug that blocks voltage operated calcium channels.</p> <p>Conclusion</p> <p>Relaxant constituents were more concentrated in ethylacetate fraction followed by chloroform, <it>n -</it>butanol and aqueous fractions that warrant for its isolation. The crude methanol extract is safe at concentration 250 mg/ml or below and results of brine shrimp cytotoxicity assay imply the plant specie may be a source of cytotoxic agents.</p