ABSTRACT
Aims: Develop an anti-tuberculosis (TB) Fixed Dose Combination (FDC) tablet containing an immediate release layer (IRL) composed of both rifampicin (RIF) and pyrazinamide (PYR) and a retarded release layer (RRL) comprised of isoniazid (INH) which would allow segregated delivery of RIF and INH. Study Design: Trials were conducted on the pre-formulations and formulations to assess the compatibility of excipients and obtain a modified release profile, for an IRL consisting of both RIF and PYR and a RRL containing INH. Place and Duration of Study: This study was performed at the Laboratory of Pharmaceutical Industrial Technology, Drug and Pharmaceutical Department, Faculty of Pharmacy, between March 2008 and April 2010. Methodology: Preformulation studies were performed on RIF and PYR, alone and in combination with excipients. The pharmacopeic attributes of the distinct layers and the FDC tablets were evaluated for hardness, friability and disintegration time. The FDC bilayer tablets were analyzed for their drug content and cumulative dissolution of the drug. Results: Fourier transform infrared, x-ray diffraction and differential scanning calorimetry results revealed the presence of amorphous and crystalline RIF forms and no potentially relevant incompatibilities were identified in the kneaded system containing RIF, PYR and excipients. In vitro drug release from the FDC tablets revealed that the intragranular addition of croscarmellose sodium into the IRL rendered a cumulative dissolution of RIF and PYR within the limits of simulated gastric fluid. And, for RRL, the most effective retardant matrix excipient was found to be hydroxypropyl methylcellulose. Conclusion: Segregated delivery of RIF and INH from bilayer tablets is an option for the development of immediate release FDC tablets and the retarded release of INH, this strategy proved suitable for preventing contact of these two drugs under acidic conditions. This finding suggested that RIF had a high in vivo bioavailability which qualifies this FDC for future bioavailability studies.
ABSTRACT
Este trabalho teve como objetivo avaliar o efeito fungitóxico do óleo essencial de capim-citronela e do seu constituinte majoritário citronelal sobre a inibição micelial do fitopatógeno Fusarium subglutinans, agente causal da fusariose da cultura do abacaxi (Ananas comosus). Para avaliar o efeito do óleo essencial no crescimento micelial do fungo, foram utilizadas seis alíquotas (0, 5, 10, 15, 20 e 25 ìL) do óleo e do citronelal que foram distribuídas na superfície do meio BDA (batata-dextrose-ágar) antes da repicagem do fungo. O crescimento micelial foi medido após 48 h de instalação do experimento e em cinco épocas de avaliação (2, 4, 6, 8 e 10 dias após repicagem). Os resultados indicaram que o óleo essencial do capim-citronela demonstrou maior efeito inibitório do crescimento micelial do fungo F. subglutinans do que o composto citronelal. Em todas as alíquotas utilizadas o óleo essencial proporcionou menor taxa de crescimento micelial do que o citronelal.
This study aimed to evaluate the fungitoxic effect of the essential oil of citronella grass and its major constituent citronellal on the inhibition of mycelial pathogen Fusarium subglutinans, the causal agent of Fusarium culture of pineapple (Ananas comosus). To evaluate the effect of essential oil in the mycelial growth of the fungus were used six rates (0, 5, 10, 15, 20 and 25 mL) of oil that were distributed on the surface of PDA medium (potato dextrose agar) before subculturing of the fungus. Mycelial growth was measured after 48 h of the experiment and five times of assessment (2, 4, 6, 8 and 10 days after subculturing). The results indicated that the essential oil of citronella grass showed higher inhibitory effect of mycelial growth of the fungus F. subglutinans than compound citronellal. In all rates used of the essential oil gave lower growth rate than the mycelial citronellal.