Preparation of novel modified-release dosage forms of diclofenac sodium and ibuprofen.

Mini-matrix multiple unit dosage forms (MUDFs) of diclofenac sodium and S(+) ibuprofen have been prepared. Normal tabletting techniques were used to form the mini-matrices prior to their enclosure in hard gelatin capsules. Four natural hydrophilic gums, namely xanthan, karaya, locust bean and carrageenan gums as well as hydroxypropyl methylcellulose (HPMC) were used as the principle release-retarding agents. Various excipients - lactose, Encompress®, cellulose acetate phthalate (CAP), Veegum F® and Avicel PH101® - were added in different proportions to further modify drug release. The diclofenac sodium mini-matrices (4.5 mm in diameter) were produced by the wet granulation method. The release profiles from several encapsulated minimatrices in phosphate buffer solution (pH 7.0) showed that xanthan, karaya and locust bean gums could sustain the release of diclofenac sodium while the carrageenan gum did not produce a satisfactory sustaining effect. The rank order of decreasing swelling rate in both axial and radial dimensions was xanthan > karaya > locust bean gum and each of these gums showed almost Fickian swelling behaviour. The solvent penetration rates were consistent with the swelling rates. However, the order of decreasing drug release and erosion rates was locust bean> xanthan > karaya gum. For each of these gums, the release behaviour was anomalous indicating that both Fickian drug diffusion and polymer relaxation were involved in the release process. The dominant mechanism depended on the nature and content of the gum, as well as the stage in the dissolution period. The study involving xanthan gum showed that the diclofenac sodium release rate declined linearly with a progressive increase in the gumcontent, without changing the release behaviour. However, for high drug: xanthan gum ratio (2:1), the release kinetics changed to Super Case II. Solubility differences between the excipients did not affect the release rate, but increasing proportions of each excipient produced a faster release rate with the release mechanism changing from anomalous to Case II and then to Super Case II transport. Mini-matrices containing HPMC produced faster drug release than those containing the three natural gums. There was no synergistic effect between xanthan and locust bean gums on the release of diclofenac sodium from mini-matrices. Variation in the stirring speed (used in the dissolution apparatus) and matrix volume had little effect on drug release, whereas the pH of the dissolution medium greatly affected the release of diclofenac sodium. Following on from the studies involving diclofenac sodium, xanthan and karaya gums were used to produce mini-matrices of S(+) ibuprofen. Excipients with good compressibility characteristics such as lactose, Encompress® and Avicel PH101® were needed in the formulations. At pH 7, higher drug release rates were obtained with karaya gum (Super Case II mechanism) compared with xanthan gum (anomalous behaviour). Solubility differences between the excipients slightly affected the release rate. Compression forces (11 - 26 kN) slightly affected the crushing strength. The minimatrices were relatively stable to variation in temperature (5 - 37°C) and relative humidity (10 - 75%) over a 2 month time period. These studies have shown that near zero-order release of diclofenac sodium and S(+) ibuprofen can be achieved using encapsulated mini-matrices formulations. The release mechanisms and release rates can be adjusted by variation of the type and content of gums and/or excipients

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

Influence of binder type and process parameters on the compression properties and microbial survival in diclofenac tablet formulations

The influence of binder type and process parameters on the compression properties and microbial survival in diclofenac tablet formulations were studied using a novel gum from Albizia zygia. Tablets were produced from diclofenac formulations containing corn starch, lactose and dicalcium phosphate. Formulations were analyzed using the Heckel and Kawakita plots. Determination of microbial viability in the formulations was done on the compressed tablets of both contaminated and uncontaminated tablets prepared from formulations. Direct compression imparted a higher plasticity on the materials than the wet granulation method. Tablets produced by wet granulation presented with a higher crushing strength than those produced by the direct compression method. Significantly higher microbial survival (pA influência do tipo de ligante e os parâmetros do processo de propriedades de compressão e sobrevivência microbiana em comprimidos de diclofenaco foram estudados utilizando uma nova goma de Albizia zygia. Os comprimidos foram produzidos a partir de formulações de diclofenaco contendo amido de milho, lactose e fosfato bicálcico. As formulações foram analisadas usando os gráficos de Heckel e Kawakita. A determinação da viabilidade microbiana nas formulações foi feita nos comprimidos contaminados e não contaminados preparados a partir de formulações. A compressão direta confere maior plasticidade dos materiais do que o método de granulação úmida. Comprimidos produzidos por granulação úmida apresentaram maior força de esmagamento do que aqueles produzidos pelo método de compressão direta. Observou-se sobrevivência significativamente maior (p<0,05) em formulações preparadas por compressão direta. A sobrevivência percentual dos esporos de Bacillus subtilis diminuiu com o aumento da concentração do agregante. O estudo mostrou que a goma de Albizia é capaz de conferir maior plasticidade aos materiais e apresentou maior redução da contaminação microbiana nas formulações. O método de compressão direta produziu comprimidos com viabilidade reduzida de contaminantes microbianos

Compaction, compression and drug release properties of diclofenac sodium and ibuprofen pellets comprising xanthan gum as a sustained release agent

Compaction and compression of xanthan gum pellets were evaluated and drug release from tablets made of pellets was characterised. Two types of pellets were prepared by extrusion-spheronisation. Formulations included xanthan gum, at 16% (w/w), diclofenac sodium or ibuprofen, at 10% (w/w), among other excipients. An amount of 500 mg of pellets fraction 1000-1400 [mu]m were compacted in a single punch press at maximum punch pressure of 125 MPa using flat-faced punches (diameter of 1.00 cm). Physical properties of pellets and tablets were analysed. Laser profilometry analysis and scanning electron microscopy of the upper surface and the surface of fracture of tablets revealed that particles remained as coherent individual units after compression process. Pellets were flatted in the same direction of the applied stress evidencing a lost of the original curvature of the spherical unit. Pellets showed close compressibility degrees (49.9% for pellets comprising diclofenac sodium and 48.5% for pellets comprising ibuprofen). Xanthan gum pellets comprising diclofenac sodium experienced a reduction of 65.5% of their original sphericity while those comprising ibuprofen lost 49.6% of the original porosity. Permanent deformation and densification were the relevant mechanisms of compression. Fragmentation was regarded as non-existent. The release of the model drug from both type of tablets revealed different behaviours. Tablets made of pellets comprising ibuprofen released the model drug in a bimodal fashion and the release behaviour was characterised as Case II transport mechanism (release exponent of 0.93). On the other hand, the release behaviour of diclofenac sodium from tablets made of pellets was anomalous (release exponent of 0.70). For the latter case, drug diffusion and erosion were competing mechanisms of drug release.http://www.sciencedirect.com/science/article/B6T7W-4FR3ND1-1/1/7bebf72d7c381f0ef545c3c20689017