Development of fast dispersing tablets of nebivolol: experimental and computational approaches to study formulation characteristics

Formulation of FDT (fast dispersing tablets) of nebivolol was optimized and evaluated using simplex lattice design (SLD). The influence of type and concentration of three disintegrants viz., Ac-Di-Sol, Primojel and Polyplasdone XL on hardness, friability and disintegration time of tablet was studied. Response surface plot and the polynomial equations were used to evaluate influence of polymer on the tablet properties. Results were statistically analyzed using ANOVA, and a p < 0.05 was considered statistically significant. Results reveal that fibrous integrity and optimal degree of substitution in Primojel and Ac-Di-Sol are mainly responsible for the hardness of the tablet. Use of Polyplasdone in higher percentage in tablet formulation may result in high friability. Increase in concentration of Ac-Di-Sol increases the disintegration time but increased concentration of Primojel in the tablet formulation decreases the disintegration time. This is also evident from model terms for disintegration time with a high 'F' value of 14.69 and 'p' value of 0.0031 (<0.05). The reason could be that Primojel has higher swelling properties and an optimum hydration capacity, which favors fast disintegration of a tablet. In conclusion, careful selection of disintegrant for FDT could improve their properties. Use of Simplex Lattice Design for formulation development could simplify the formulation process and reduce the production cost.

Otimizou-se e avaliou-se formulação de comprimidos de dispersão rápida (CDR) de nebivolol, usando planejamento de grade simplex (PGS). Estudou-se a influência do tipo e da concentração de três desintegrantes viz, Ac-Di-Sol, Primojel e Poliplasdona XL, na dureza, friabilidade e tempo de desintegração do comprimido. O gráfico de superfície de resposta e as equações polinomiais foram utilizados para avaliar a influência do polímero nas propriedades do comprimido. Os resultados foram analisados estatisticamente por ANOVA, considerando-se p < 0,05 como estatisticamente significativo. Os resultados revelam que a integridade das fibras e o grau de substituição ótimo no Primojel e Ac-Di-Sol são os principais responsáveis pela dureza do comprimido. O uso de Poliplasdona em maior porcentagem na formulação pode produzir friabilidade elevada. O aumento de Ac-Di-Sol aumenta o tempo de desintegração, mas o aumento da concentração de Primojel na formulação diminui o tempo de desintegração. Isto é, também, evidente no modelo de tempo de desintegração com alto valor de "F" de 14,69 e "p" de 0,0031 (< 0,05). A razão poderia ser que o Primojel tem maiores propriedades de intumescimento e ótima capacidade de hidratação, favorecendo a desintegração rápida do comprimido. Em conclusão, a cuidadosa seleção de um desintegrante para CDR poderia aprimorar suas propriedades. O uso do PGS para o desenvolvimento da formulação poderia simplificar o processo de formulação e reduzir o custo de produção.

Application of Simplex Lattice Design in Formulation and Development of Buoyant Matrices of Dipyridamole.

The present study describes the design and development of buoyant matrices of dipyridamole. The matrices were prepared by direct compression method using simplex lattice design as an optimization technique. Amount of HPMC K4M (X1), sodium bicarbonate (X2) and ethyl cellulose (X3) were used as the independent variables where floating lag time (Y1) and percentage drug release at 6h (Y2) were considered as the response variables. As per the simplex lattice design total 7 formulations were formulated. Matrices were evaluated for physical parameters, in-vitro buoyancy, in-vitro drug release, water uptake studies. Drug release data was fitted into different kinetic models. The results of response variables were statistically evaluated using design expert 8.0 software. Polynomial models were generated for all the response variables using multiple linear regression analysis (MLRA) approach. A statistical model incorporating 7 interactive terms was used to evaluate the responses. The results of response variables are expressed for model analysis by Scheffe’s special cubic model. Graphical representation was done by response surface plots and contour plots. The resulted model equation showed that factor X1 responsible for prolongation of drug release. On the basis of acceptance criteria the formulation coded by DP3 was selected as a promising formulation from the simplex lattice batches which fitted best to zero order release kinetic model.