Improvement on compactibility of the alcoholic extract of Zingiberis Rhizoma by co-spray drying with HPMC / 中国中药杂志

Aiming to solve the poor compactibility of the alcoholic extract of Zingiberis Rhizoma(ZR), this study explored the feasibility of its physical modification using co-spray drying with a small amount of hydroxypropyl methyl cellulose(HPMC). Based on the univariate analysis, the influence of two independent variables(the HPMC content in the product and the solid content of spray material) on the powder properties and tablet properties of the dried product was investigated by the central composite design. With the tensile strength and disintegration time of the tablets as the evaluation indexes, the optimal prescription was determined as follows: the HPMC content was 15% and the solid content of spray material was 25.6%. The accuracy of the regression model established for predicting tensile strength and disintegration time of tablets was verified, and the results revealed that the measured values were close to the predicted ones with deviations of 0.47% and-8.2%, indicating good prediction and reproducibility of the model. The tensile strength(4.24 MPa) of tablets prepared with the optimal prescription was 3.59 times that(1.18 MPa, far lower than the baseline of 2 MPa for qualified tablets) with the spray-dried powder of the ZR. On the other hand, due to the addition of HPMC, the disintegration time of tablets increased from 7.3 min to 24.6 min. On the whole, this study provided a new strategy to solve the common problem of poor compactibility of raw Chinese medicinal materials, which facilitated the successful preparation of Chinese medicinal tablets with high drug loads.

Improving compactibility properties of Lonicera Japonica Flos by Plasdone S-630 / 药学学报

To improve the fluidity and compactibility properties of raw powders of traditional Chinese medicine by particle modification technology, Lonicera Japonica Flos was used as a model drug, fluidized bed bottom spray technology was used, and Plasdone S-630 was used as a modifier to prepare modified particles. The powder properties, tablet compactibility parameters, disintegration time and dissolution were measured. The surface morphology of the powder particles before and after modification and compressed tablets were characterized by combining with scanning electron microscopy technology. The results showed that the particle size of Lonicera Japonica powder has been increased after particle modification, the fluidity, compressibility and compactibility of the powder have been improved to some extent, the disintegration time has also been reduced, and the dissolution in vitro is not affected. Therefore, this study can provide reference and ideas for the common problem that raw powder of traditional Chinese medicine that cannot meet the needs of preparation production due to poor powder properties such as fluidity and compressibility.

Functionality of Benecel K4M/Carbopol 971P NF matrices in direct compression tablets for controlled release.

The aim of this work is the assessment of the eventual enhancing effects of Carbopol 971P NF on the performance of Benecel K4M as a controlled release agent and its impact on other technological properties such as compactibility and powder flowability. The effect of Carbopol 971P NF and Benecel K4M in the performance of metronidazole tablets with controlled release was assessed using dissolution and compactibility profiles and the flowability of powders. Benecel K4M produces release profiles with an average exponent n=0.711 while Carbopol 971P NF displays average values of n=1.19. The values for tablets containing equal parts of Carbopol 971P NF and Benecel K4M was an average of n=0.947. Metronidazole tablets containing the Benecel K4M/Carbopol 971P NF blend shows a compactibility 2-3 times higher than tablets containing only Benecel K4M. Metronidazole/Benecel K4M blends flow sufficiently at all studied polymer proportions (≤ 30%) while admixtures of metronidazole/Benecel K4M with Carbopol 971P NF flow sufficiently only at polymer proportions ≤ 17%. Carbopol 971P NF enhances the overall performance of Benecel K4M in the same way as Noveon AA1 does, it reduces better the drug release and improves the compactibility, although decreases the flowability.

Contrasting the crospovidones functionality as excipients for direct compression

Specific values of technological properties of excipients allow the establishment of numerical parameters to define and compare their functionality. This study investigates the functionality of Polyplasdones XL and XL10. Parameters studied included tablet disintegration profiles, compactibility profiles and powder flow. The results allowed the establishment of quantitative surrogate functionalities of technological performance, such as absolute number, and as a value relative to the known microcrystalline cellulose type 102. Moreover, the establishment of an explicit functionality to improve the technological performance of two diluents and a model drug was investigated, as was setting up of these functionalities, as quantitative values, to determine the input variables of each material and its probable functionality in a drug product. Disintegration times of pure Polyplasdone XL and its admixtures were around half that of Polyplasdone XL10. The improvement in tablet compactibility was 25-50% greater for Polyplasdone XL10 than Polyplasdone XL. Crospovidones proportions of up to 10% have little effect on the flow properties of other powders, although pure Polyplasdone XL10 and its admixtures display compressibility indexes about 20% greater than Polyplasdone XL. The observed results are in line with a smaller particle size of Polyplasdone XL10 compared to Polyplasdone XL.

Os valores específicos de propriedades tecnológicas de excipientes permitem o estabelecimento de parâmetros numéricos para definir e comparar a sua funcionalidade. Este estudo investiga a funcionalidade dos excipientes. Os parâmetros estudados foram perfis de desintegração dos comprimidos, perfis de compactação e fluxo de pó. Os resultados permitiram expressar o desempenho tecnológico através de valores absolutos e valores relativos à conhecida celulose microcristalina tipo 102. Do mesmo modo, permitiram estabelecer uma funcionalidade explícita para melhorar o desempenho tecnológico de dois diluentes e um fármaco modelo. A criação destas funcionalidades, como valores quantitativos, permite conhecer as variáveis de entrada de cada material e sua provável funcionalidade em um medicamento. Os tempos de desintegração do Poliplasdone XL e das suas misturas são cerca da metade do observado para as misturas com o Poliplasdone XL10. Melhoria da compressão de comprimidos que contêm Polyplasdone XL10 é 25-50% maior do que o Polyplasdone XL. Crospovidonas em proporções de até 10% têm pouco efeito sobre as propriedades de fluxo dos outros pós embora o Poliplasdone XL10 e suas misturas exibam índices de compressibilidade cerca de 20% maior do que o Poliplasdone XL. Os resultados observados estão em sintonia com o menor tamanho de partícula do Poliplasdone XL10, em comparação com o Poliplasdone XL.

Noveon AA1 as enhancer of HPMC as a direct compression matrix for controlled release.

This work aimed the assessment of the effect of different proportions of Noveon AA1 on performance of HPMC as a controlled release agent for direct compression tablets. The functionality of polymer blends was determined using dissolution profiles, compactibility profiles and the powders compressibility index. Ten percent HPMC allows a metronidazole release after 3 h of 85%, an exponent n=0.48 and a release constant K=6.9. The increasing polymer substitution by Noveon AA1 decreases drug dissolution up to 36%, increases the exponent to 1.0 and decreases the release constant to 0.2%. The metronidazole/HPMC blend shows a slower increasing and a lower potential of tablets compactibility (20 N) while its increasing substitution by Noveon AA1 attains faster increasing and higher potential compactibilities (39 N). The metronidazole/HPMC (90:10) blend shows a low compressibility index (14%) that increases up to 33.2% with increasing Noveon AA1 proportions. Noveon AA1 proportions ≤ 5% display good/passable powder flowabilities. Noveon AA1 enhances the overall controlled release performance of HPMC, inducing zero order release patterns without lag or burst effects and reducing drug release more efficiently. Noveon AA1 also improves the compactibility of metronidazole/HPMC blends, however, decreases their flowability; flowability is acceptable only at lesser polymer proportions.

Multivariate analysis on micromeritic properties of Sarcandrae Herba Granule and its correlation with tablet compactibility / 中草药

Objective: To investigate the correlations between micromeritic primary properties and compactibility of granules produced by wet granulation of Sarcandrae Herba with soluble starch and microcrystalline cellulose (MCC). Methods: Micromeritic primary properties and compactibility of granules produced by wet granulation which was obtained by different prescriptions and processes were determined. Particle size (D90), specific surface area (SSA), pore volume (PV), moisture content (MC), bulk density (BD), tap density (TD), tap index (TI), angle of repose (AOR), and Kawakita equation parameters a and b were used as evaluation indexs to study the micromeritic primary properties of granulation. The tensile strengths of granules at 5, 10, 15, 20, 25, and 30 kN pressure were used as the indexs to evaluate the compactibility of granules produced. Multivariate analysis was applied to evaluating the correlations between micromeritic primary properties and compactibility of granules produced. Results: The micromeritic primary properties of granules could be extracted as two principal components, morphology parameter and compressibility parameter. The significant effects on the tablet compactibility are the compressibility, moisture, and surface morphology of granules produced. Conclusion: Multivariate data analysis could make the quick and easy classification of Sarcandrae Herba Granule. The correlation between granules micromeritic primary properties and tablet compactibility is given. By controlling compressibility, moisture, and surface morphology of granules produced, the tablets with good compactibility can be obtained.

Functionality of GalenIQ 721 as excipient for direct compression tablets.

The purpose of the work is the comparative evaluation of GalenIQ 721, against known excipients such as Pharmatose M200 and Alfacel type 102. The evaluated parameters included compactibility curves, tablet ejection pressure, disintegration time and flowability of individual powders and mixtures of the excipients and amoxicillin. The surrogate and explicit compactibility of Alfacel 102 (492 N; 7.9 N) is superior, followed by GalenIQ 721 (310 N; 0.93 N) and Pharmatose M200 (203 N; -2.8 N). The lubricity of Alfacel 102 is superior (ejection pressure - Pe=0.590 MPa), followed by GalenIQ 721 (Pe=6.45 MPa) and Pharmatose M200 (Pe=6.51 MPa). Disintegrability of tablets was better by GalenIQ (0.33 s/N), followed by Alfacel 102 (2.48 s/N) and Pharmatose M200 (4.47 s/N).GalenIQ 721 displays a powder fluidity of (14.4 g/s), followed by Alfacel 102 (7.88 g/s) and Pharmatose M200 (0.99 g/s). The tableting functionality of GalenIQ 721 is better than that of Pharmatose M200 but inferior of that of Alfacel 102. Although the GalenIQ 721 characteristics, predominantly brittle, are expected to be more stable to changes in formula composition and process conditions than those of Alfacel 102, plastic behavior.