Development of meloxicam formulations utilizing ternary complexation for solubility enhancement

Meloxicam [an oxicam derivative], a relatively new cyclo-oxygenase inhibitor, is a member of enolic acid group of non-steroidal anti-inflammatory drugs. It is generally used in the treatment of rheumatoid arthritis, osteoarthritis and other joint pains. Meloxicam is practically insoluble in water [8 microg/ml], which directly influences the C[max], T[max], as well as the bioavailability of the drug. In the present study, an attempt has been made to improve the dissolution of Meloxicam by preparation of its solid dispersion using p-cyclodextrin blended with various water soluble polymer carriers i.e., HPMC [methocel IH], methylcellulose [400cps], PVP K30, HPMC [K[4]M], HPMC [50cps]. It is reported that when small amount of water soluble polymer is added to beta-cyclodextrin, its nature of solubilization significantly increases due to increase in the apparent complex stability constant. Phase solubility studies were carried out to evaluate the solubilizing power of beta-cyclodextrin along with various water soluble polymers. The solid dispersion was prepared and formulated into tablets and suspension, which were evaluated on the basis of various official tests. All the studies suggest that formulations of Meloxicam utilizing solid dispersion technique significantly enhances solubility [90 microg/ml] of the drug and results in superior formulations of the drug by using beta-cyclodextrin blended with 0.12% w/w HPMC [Methocel IH]. Ternary complexation is a valuable tool for solubility enhancement of drugs

Effect of processing variables and in-vitro study of microparticulate system of nimesulide

Microparticulate systems of nimesulide (NIM) were prepared by modified solvent evaporation method using different variables such as polymer: drug (NIM) ratios (cellulose acetate, CA: nimesulide, NIM) (1:9, 1:6 and 1:3), agitation speeds (500-1500 rpm) and stirring time (15-30 min). The effects of processing variables were evaluated by microparticle size and entrapment efficiency. The average microparticle size increases from 66.8±1.45 to 87.3±1.06 µm with increase in the polymer concentration while reduces with increase in agitation speed and stirring time; but at the too higher speed gives irregular shape of particles. The highest entrapment efficiency (77.83±0.51 percent), size uniformity, free flowability, i.e., angle of repose (23.5±0.4º) and compressibility index (14.2±0.6 percent), of microparticles were found with 1:6 (polymer: drug ratio), at 1000 rpm and 20 min stirring time among all prepared microparticles (P < 0.05). The in-vitro drug release study of microparticles with optimized processing variables (agitation speed and time) were carried out and compared with conventional and marketed SR tablets. The conventional tablet releases maximum drug within 4 h while microparticulate system releases more than 14 h. All formulations followed first order release kinetic and diffusion controlled drug release (Higuchi model). These microparticles are stable at room temperature (25±1 ºC) but agglomerate at elevated temperature (50±1 ºC) by softening and fusion of the polymer observed under SEM study.

Prepararam-se sistemas microparticulados de nimesulida (NIM) pelo método modificado de evaporação do solvente usando diferentes variáveis, tais como proporções polímero fármaco(NIM) (acetato de celulose, CA: nimesulida, NIM) (1:9, 1:6 e 1:3), velocidades de agitação (500-1500 rpm) e tempo de agitação (15-30 min). Os efeitos das variáveis do processo foram avaliados pelo tamanho da partícula e pela eficiência no encapsulamento. O tamanho médio das micropartículas aumenta de 66,8±1,45 a 87,3±1,06 µm com o aumento na concentração de polímero, enquanto reduz com o aumento da velocidade e do tempo de agitação, mas velocidades mais altas resultam em partículas de formas irregulares. A eficácia de encapsulamento mais alta (77,83±0,51 por cento), uniformidade de tamanho, fluxo livre, isto é, ângulo de repouso (23,5±0,4º), e índice de compressibilidade (14,2±0,6 por cento), das micropartículas foram encontrados com a proporção de 1:6 (polímero:fármaco), a 1000 rpm e 20 min de tempo de agitação entre todas as micropartículas preparadas (P < 0,05). O estudo da liberação do fármaco das micropartículas in vitro com variáveis do processo otimizadas (velocidade de agitação e tempo) foi desenvolvido e comparado com comprimidos convencionais e comercializados SR. O comprimido convencional libera o máximo de fármaco dentro de 4 h enquanto o sistema microparticulado libera em mais que 14 h. Todas as formulações seguiram cinética de liberação de primeira ordem e liberação do fármaco controlada pela difusão (modelo de Higuchi). Estas microparticulas são estáveis à temperatura ambiente (25±1 ºC), mas se aglomeram a temperaturas elevadas (50 ± 1 ºC) por meio do amolecimento e fusão do polímero observada sob o estudo SEM.