ABSTRACT
The symptoms of some diseases show circadian rhythms, such as the morning stiffness associated with pain at the time of awakening in rheumatoid arthritis. Therapy for such diseases doesn't require immediate release or sustained release of medicament. In such therapies, pulsatile drug release is more suitable with a programmed drug release. The purpose of this research was to formulate press-coated aceclofenac tablets for pulsatile drug delivery with a distinct delay time of no drug release and release of the drug when it is more likely desired (i.e., after 5 to 6 h). Immediate release core tablets having aceclofenac were formulated. Three formulations, F1, F2, and F3, were prepared with variable concentrations of sodium croscarmellose. Pre- and post-compression tests were performed on the core tablets. The selection criteria included the lowest disintegration time as a requirement of pulsatile drug delivery with an immediate release core and a delayed release coat. The disintegration times of F1, F2, and F3 were 120 s, 60 s, and 15 s, respectively. Therefore, the F3 formulation was selected as the core tablet formulation because it had the shortest disintegration time (15 s). The core tablets were press-coated using different polymers, such as HPMC K100M, Eudragit L100, HEC, and HPMC E5. The polymers were used in the coatings to hinder the release of the core for the desired time. 36 formulations of polymer were prepared: A1 to A10 had HPMC K100M and Avicel PH102; formulations B1 to B6 had HPMC K100M, Eudragit L100, and Avicel PH102; formulations C1 to C7 had HPMC K100M and hydroxyethyl cellulose; formulations D1 to D7 had HPMC K100M and HPMC E5; and formulations E1 to E6 had changed the coating weight of the formulation used for D6 (having HPMC K100M and HPMC E5 in the ratio of 12.5% to 87.5%). Evaluations of the press-coated tablets were carried out through thickness, hardness, weight variation, friability, and in vitro dissolution tests. These parameters concluded that the formulation of E6, having HPMC K100M and HPMC E5 in the ratio of 12.5% to 87.5% at 600 mg weight, was the most optimum formulation as it showed 3.5% drug release after 4 h, 21.4% drug release after 5 h, and 99.27% drug release after 6 h.
ABSTRACT
Two promising antibiotics, JF-A and JF-B were isolated from the chloroform extract of a Banglaeshi Streptomyces strain. The mean zones of inhibition produced by the chloroform extract (400 microg/disc), JF-A (200 microg/disc) and JF-B (200 microg/disc) against 19 pathogenic bacteria were found to be 9-50, 12-38 and 10-41 mm while those produced by a standard antibiotic, kanamycin were 11-40 mm at 30 microg/disc. MICs of JF-A and JF-B were determined to be 64 microg/ml against Bacillus subtilis and 64 and 128 microg/ml against Shigella sonnei, respectively. The extract and the antibiotics were also tested for cytotoxicity against Artemia salina nauplii and LC50 values of 23.26, 18.05 and 32.27 microg/ml were obtained. 90% mortality of shrimp nauplii was observed at 69.18, 50.12 and 110.91 microg/ml, respectively. In a potato disc bioassay, the chloroform extract at 25 microg/disc demonstrated 37.39% inhibition of crown gall tumour induced by G -ve Agrobacterium tumefaciens B6 and the result was statistically significant (P < 0.05). The sub-acute toxicity studies on the JF-A and JF-B reflected innocuous nature of these antibiotics on hepatic, renal and haemopoietic system of rats at 1 mg/kg b.w. on daily administration for 21 consecutive days. This is also confirmed by detailed histopathological studies. No mortality was observed in experimental animals.
