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.

Estudo de propriedades físico-químicas envolvidas no processo de compactação de uma formulação experimental contendo zidovudina / Study of physical-chemical properties involved in the compaction process of an experimental formulation containing zidovudine

Estudo das propriedades físico-químicas envolvidos no processo de compactação de uma formulação experimental contendo como fármaco modelo a zidovudina. O objetivo foi caracterizar o comportamento físico-químico de comprimidos produzidos por compressão direta usando-se diferentes pressões de compactação. Nas análises foram empregadas metodologias convencionais e não convencionais. A metodologia não convencional foi o uso da técnica da atenuação de raios-gama na determinação da porosidade. As metodologias convencionais utilizadas foram os testes de friabilidade, dureza e dissolução. Os modelos teóricos utilizados para explicar o comportamento físico-químico da formulação sob compressão são os proposto por Heckel e Walker. Os estudos mostraram que o processo de densificação é governado principalmente por deformações do tipo plásticas e pressões em torno de 246MPa são suficientes para induzir deformação plástica e consolidação do sistema compactado. Os resultados da análise de Walker indicam que a formulação tem propriedades de compressão que podem ser melhoradas.

This paper presents a study of the physical-chemical properties involved in powder compaction of an experimental formulation containing as model drug the zidovudine. The aim of this work was to characterize the physical-chemical behavior of experimental tablets produced by direct compression applying different strengths. In these analyses were employed conventional and non-conventional methodologies. The non-convectional methodology was the use of gamma-ray attenuation technique for tablet porosity determination. The conventional methodologies used were the tests of hardness, friability and dissolution. The theoretical models used to explain the physical-chemical behavior of the formulation under compression were those proposed by Heckel and Walker. These tests showing that the densification process is to take mainly by plastic deformation and pressures about 246 MPa are enough to produce robust tablets. Results obtained from the analysis of the Walker equation, indicate that the formulation has compression properties that could be improved.

Performance equivalence study of sodium starch glycolate, modified maize starch and maize starch as disintegrants in paracetamol tablet formulation

Fierce price competition informed the reappraisal and reformulation of paracetamol tablet. Sodium starch glycolate [SSG] was implicated in the high cost and needed to be replaced. The use of modified maize starch [MMS] produced by cold, dilute acid hydrolysis of maize starch [MS] offered good and cheaper alternative. Evaluation of different disintegrants using 5 batch formulations coded SSG-3, MS-3, MMS-3, MMS-6 and MMS-9 and characterization of resultant tablets showed that interchanging SSG with MMS resulted in no deleterious therapeutic consequences. Inclusion of 6% MMS in the paracetamol formulation gave tablets that exhibited good mechanical and dissolution properties comparable to the tablets produced with 3% sodium starch glycolate. Indeed, at 95% confidence level, t-test which compares the p-value [?0.05] of dissolution of the batch formulations returned values of 0.000056 for MS-3, 0.0182 for MMS-3, 0.0965 for MMS-6 and 0.1433 for MMS-9. The values confirmed the significant differences between batch SSG-3 and batches MS-3 and MMS-3 and no difference of any significance in batches MMS-6 and MMS-9. Hence MS and MMS at 3% level can not effectively replace SSG at 3% level. The poor friability [1.12%] as well as higher disintegration time [16 minutes, 54 seconds], both higher than official limits of<1% and ?15 minutes respectively, would not also allow the use of MMS at 3 and 9% level as substitutes for 3% SSG. Thus, only MMS at 6% inclusion level can interchange with SSG 3%. Cost-benefit analysis showed that over 9% cost reduction is achieved by the replacement without compromising both physical and chemical qualities of the resultant tablets which include mean dissolution time [MDT] 50% of 4.5 minutes and dissolution of 103.87% in 30 minutes

Formulation development and optimization of Ibuprofen tablets by direct compression method

Ibuprofen is widely used as a prescription and non-prescription medicine. The aim of study is to prepare Ibuprofen tablets [200mg] using direct compression technique which is now days considered a cost effective and simple method of manufacturing. It is considered as an appropriate method for hygroscopic and thermolabile substances. In order to obtain the best, optimized product, nine different formulations were developed. Diluent [X1], disintegrant [X2] and lubricant [X3] were taken as independent variables. Weight variation [Y1], thickness [Y2], length and width [Y3], hardness [Y4], friability [Y5], disintegration [Y6], dissolution [Y7] and pharmaceutical assay [Y8] were studied as response variables. The results of all nine formulations were found within the acceptable limits conforming to those given in official compendia. However, F-6 was selected as an optimized product on the basis of high dissolution [99.05%] and Assay [100.04%]. The variation of weight among the tablets of F-6 was least which showed best ratio of excipients in the formulation. Optimization has proven as an effective tool in product development. This is because no clear relationship exists between the variables

comparative study of dissolution characteristics of polymeric and wax granulations of theophylline and their tablets

Matrix [non disintegrating] granules of theophylline have been formed and their dissolution characteristics investigated for sustained release application. The polymeric granulations were formed by massing the drug powder with a concentrated [40%w/w] ethanolic solution of an acrylatemethacrylate copolymer [ERS100R]. Wax granulations were also formed by massing the drug powder with previously melted carnuba wax followed by screening and drying. The content of polymer or wax in the resulting granules was 16.7%w/w. Conventional granules of theophylline were formed by massing the drug powder with starch mucilage [20%w/v]. Resulting granules were subjected to particle size analysis and in vitro dissolution tests. The granules were further compressed to tablets [weight 500 +/- 4.2mg each] at a constant load [30 arbitrary units on the load scale]. The tablets were subjected to hardness, disintegration and dissolution tests. The dissolution kinetics were also considered. The mean granule size was 646.5 +/- 4.3 micro m [convention al], 821.4 +/- 4.8 micro m [polymeric granulations] and 892.7 +/- 5.4 micro m [wax granulations], the matrix granules were therefore larger than the conventional granules. Dissolution of the granules generally followed a first order rate kinetic. The rate constant [k1] for the conventional, polymeric and wax granulations were [h-1]: 0.53, 0.31 and 0.27 respectively. Thus, the wax granulations appeared to be more effective than the polymeric granulations in retarding drug release from the granules but the difference was not statistically significant [p > 0.05]. The tensile strength of tablets derived from the conventional, polymeric and wax granulations were [MNm-2] 0.85, 1.68 and 1.96 respectively, indicating that the matrix granules [compared with the conventional granules] produced harder tablets at the same compression load. The corresponding first order dissolution rate constants were [h-1]: 0.46, 0.28 and 0.21. Thus, tableting of the matrix granules produced a slight but significant decrease in dissolution rates, attributabl e to the disintegration of the tablets to more compact particles

Development of fast release mebeverine hydrochloride tablets

The drug release from five commercial br and s of mebeverine hydrochloride tablets was tested. The results revealed the presence of large interbr and and intrabatch differences. These differences in drug release were attributed mainly to the physical behavior of the raw material during the production processes. Mebeverine hydrochloride crystals prepared from benzene were used for the preparation of four tablet formulations by the direct compression technique. The release of the drug from formulated tablets was superior to most of the commercially available br and s