Tableting
Dotaz
Zobrazit nápovědu
Despite the high quantities of tablets produced daily, many tableting processes are still operated at sub-optimal settings and hence lack the necessary flexibility to mitigate for possible process deviations. However, to ensure this flexibility on tableting throughput it is important to select the most robust feed frame design and settings regarding die-filling. In this research study, four paddle designs for a two-compartment forced feeder (equipped with a metering and a feeding paddle wheel) were evaluated at a wide range of process-settings (i.e. tableting speed, paddle speed, overfill level) and feed frame features (i.e. deaeration) for their impact on the die-filling step of a poorly flowing model formulation (i.e. MCC 101) using a quality-by-design approach. No benefit on die-filling was observed when using higher speeds of the metering paddle wheel compared to the feeding paddle wheel, and no convincing arguments were obtained to use the feed frame deaeration opening. Some combinations of paddle design and process-settings significantly increased the risk for inconsistent die-filling (i.e. high tablet weight variability) which can therefore limit the efficiency of the tableting process. The approach used in this study enabled to compare the paddle designs for their die-filling performance in function of varying tableting speeds, eventually resulting in the selection of a feed frame design that is most robust and therefore will provide a uniform die-filling over a wide range of throughputs. Selection of the most robust parameters is an important prerequisite for the ability of using the rotary tablet press as an agile unit-operation.
- MeSH
- celulosa chemie MeSH
- prášky, zásypy, pudry MeSH
- příprava léků přístrojové vybavení MeSH
- tablety * MeSH
- tvrdost MeSH
- Publikační typ
- časopisecké články MeSH
With the current transformation of the pharmaceutical industry towards continuous manufacturing, there is an inherent need to embrace this concept already during the early stages of drug formulation. Therefore, this research paper investigated the feasibility of using miniaturized forced feeders on a high-speed rotary tablet press with the intention of downscaling the tableting process. Forced feeders with a reduced volume (up to 46% compared to the conventional two-compartment forced feeder) were designed by either sealing one compartment (i.e. R&D1) or lowering of the compartment height (i.e. R&D2). These feed frame designs were thoroughly analysed in combination with two paddle types over a wide range of process-settings (i.e. tableting speed, paddle speed, direction of paddle rotation, overfill-level). A poorly flowing model powder (i.e. MCC 101) was deliberately selected as challenging formulation. Empirical modelling of feed frame R&D1 revealed a positive impact on the die-filling variability when the radial curved cuboid paddles rotated in counterclockwise direction at high paddle speed. Moreover, a strong resemblance between the R&D2 feed frame and the conventional forced feeder was observed during multivariate data analysis, indicating that this miniaturized type could be used during downscaling studies of the conventional tableting process. The potential of this forced feeder was acknowledged by the similar trends in die-filling variability with respect to varying process settings, when a design-of-experiments (DOE) was performing including feed frame type as a qualitative factor. Overall, it was concluded that both types of miniaturized forced feeders can be used on a high-speed rotary tablet press when lower material consumption rates are desired while the R&D2 feed frame bears the highest predictability regarding the die-filling uniformity in the conventional larger two-compartment forced feeder.
- MeSH
- celulosa MeSH
- farmaceutická technologie metody MeSH
- miniaturizace MeSH
- pomocné látky MeSH
- tablety * MeSH
- Publikační typ
- časopisecké články MeSH
Co-processed dry binders for ODTs are important multifunctional excipients for tablet manufacturing by direct compression. Testing their binary mixtures with lubricants is an important aspect of their use in combination with drugs. The aim of this study was to evaluate the rheological and compression properties of lubricated mixtures of co-processed dry binders Parteck® ODT, Prosolv® ODT G2 and Ludiflash®, and subsequently also the compactability and disintegration time of the tablets made thereof. The lubricants employed were magnesium stearate and sodium stearyl fumarate in the concentrations of 0.5% and 1%. The best flowability was shown by Prosolv® ODT G2 combined with magnesium stearate in the concentration of 0.5%. Lubricated mixtures with Prosolv® ODT G2 showed a lower angle of internal friction as well as lower pre-compression energy values. The values of plastic deformation energy were the highest in the case of Prosolv® ODT G2, which was also reflected in the highest tablet strength. On the contrary, the ejection force values were the lowest for this co-processed dry binder. Magnesium stearate reduced the ejection force more effectively than sodium stearyl fumarate. Prosolv® ODT G2 tablets exhibited the highest tensile strength and shortest disintegration time.
- MeSH
- lubrikanty * MeSH
- pevnost v tahu MeSH
- pomocné látky * MeSH
- tablety MeSH
- Publikační typ
- časopisecké články MeSH
The paper evaluates and compares the compressibility and compactibility of directly compressible tableting materials for the preparation of hydrophilic gel matrix tablets containing tramadol hydrochloride and the coprocessed dry binders Prosolv® SMCC 90 and Disintequik™ MCC 25. The selected types of hypromellose are Methocel™ Premium K4M and Methocel™ Premium K100M in 30 and 50 % concentrations, the lubricant being magnesium stearate in a 1 % concentration. Compressibility is evaluated by means of the energy profile of compression process and compactibility by the tensile strength of tablets. The values of total energy of compression and plasticity were higher in the tableting materials containing Prosolv® SMCC 90 than in those containing Disintequik™ MCC 25. Tramadol slightly decreased the values of total energy of compression and plasticity. Tableting materials containing Prosolv® SMCC 90 yielded stronger tablets. Tramadol decreased the strength of tablets from both coprocessed dry binders.
- MeSH
- celulosa chemie MeSH
- deriváty hypromelózy chemie MeSH
- gely MeSH
- hydrofobní a hydrofilní interakce MeSH
- kyseliny stearové chemie MeSH
- mechanické jevy MeSH
- opioidní analgetika chemie MeSH
- pevnost v tahu MeSH
- pevnost v tlaku MeSH
- pomocné látky chemie MeSH
- přenos energie MeSH
- příprava léků * MeSH
- pružnost MeSH
- tablety MeSH
- tramadol chemie MeSH
- viskozita MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Klíčová slova
- stlačení,
- MeSH
- farmaceutická chemie MeSH
- fumaráty MeSH
- hydrofobní a hydrofilní interakce MeSH
- laktosa * MeSH
- lubrikanty MeSH
- oxid křemičitý MeSH
- pomocné látky MeSH
- povrchové vlastnosti MeSH
- stearany MeSH
- tablety * MeSH
- teoretické modely MeSH
- testování materiálů * MeSH
- Publikační typ
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Práce se zabývá studiem pevnosti a doby rozpadu tablet ze dvou typů přímo lisovatelného xylitolu a to Xylitabu 100 a Xylitabu 200 v závislosti na lisovací síle, přídavku dvou typů mazadel v jedné koncentraci a dvou typů léčivých látek. Tablety se lisovaly silou 6, 8, a 10 kN, tabletoviny s léčivy pouze 10 kN. Použitá mazadla byla stearan hořečnatý a stearylfumarát sodný v koncentraci 1 %, léčivé látky kyselina askorbová a kyselina acetylsalicylová v koncentraci 50 %. Pevnost tablet rostla s lisovací silou. Výlisky z Xylitabu 100 měly pevnost vyšší a více sníženou přídavkem mazadel než výlisky z Xylitabu 200, u něhož na rozdíl od Xylitabu 100 více snižoval pevnost stearan hořečnatý. Doba rozpadu byla delší v případě výlisků s Xylitabem 200, rostla s lisovací silou, kromě Xylitabu 200 se stearanem hořečnatým a byla prodloužena mazadly, více stearanem hořečnatým. Výlisky s oběma léčivy byly pevnější a s kratší dobou rozpadu v případě Xylitabu 100. Významně vyšší pevnost a delší dobu rozpadu měly tablety s kyselinou acetylsalicylovou.
The paper deals with the study of tensile strength and disintegration time of tablets from two types of directly compressible xylitol, Xylitab 100 and Xylitab 200, in dependence on compression force, addition of two types of lubricants in one concentration, and two types of active ingredients. Tablets were compressed using the compression forces of 6, 8, and 10 kN, in the case of tableting materials with active ingredients, only 10 kN. The lubricants employed were magnesium stearate and sodium stearyl fumarate at the concentration of 1%, the active ingredients, ascorbic acid and acetylsalicylic acid at the concentration of 50%. The strength of tablets increased with compression force. Compacts from Xylitab 100 possessed a higher strength and it was more decreased by added lubricants than compacts from Xylitab 200, in which, in contrast to Xylitab 100, magnesium stearate decreased strength more. Disintegration time was longer in the case of compacts with Xylitab 200; it increased with compression force, except in those with Xylitab 200 with magnesium stearate and it was prolonged in the case of the presence of lubricants, more in the case of magnesium stearate . Compacts with both active ingredients were stronger and possessed a shorter disintegration time in the case of Xylitab 100. A significantly higher strength and a longer disintegration time was observed in the tablets with acetylsalicylic acid.
- MeSH
- financování organizované MeSH
- pevnost v tahu MeSH
- tablety analýza MeSH
- xylitol analýza chemie MeSH
- Publikační typ
- srovnávací studie MeSH
Prostřednictvím pevnosti tablet v tahu a hodnot Weibullových modulů byl studován vliv inkorporace rozdílné koncentrace stearanu horečnatého (0; 0,4; 0,8 a 1,2 %) na texturu tablet z Avicelu PH 101. Bylo zjištěno, že se zvyšujícím se lisovacím tlakem se zvyšuje snížení pevnosti tablet v tahu, přičemž mezi koncentracemi 0,4 a 0,8 % stearanu nebyl zjištěn významný rozdfl ve snížení pevnosti. Inkorporace stearanu horečnatého do tabletoviny, snížením tření mezi částicemi, minimalizuje možnost incidence výraznějších poruch v textuře tablet.
The effect of the incorporation of different concentrations of magnesium stearate (0, 0.4, 0.8, and 1.2 %) on the texture of the tablets from Avicel PH101 was investigated by means of the examination of their tensile strength and the values of Weibull's modules. It has been foimd that with an increasing forming pressure the decrease in the tensile strength of tablets is increased. No significant difference in the decrease in tensile strength was found between stearate concentrations of 0.4 and 0.8 %. The incorporation of magnesium stearate into the tableting material, by decreasing the friction between the particles, minimizes possible incidence of more marked disorders in the texture of tablets.
As is the case with batch-based tableting processes, continuous tablet manufacturing can be conducted by direct compression or with a granulation step such as dry or wet granulation included in the production procedure. In this work, continuous manufacturing tests were performed with a commercial tablet formulation, while maintaining its original material composition. Challenges were encountered with the feeding performance of the API during initial tests which required designing different powder pre-blend compositions. After the pre-blend optimization phase, granules were prepared with a roller compactor. Tableting was conducted with the granules and an additional brief continuous direct compression run was completed with some ungranulated mixture. The tablets were assessed with off-line tests, applying the quality requirements demanded for the batch-manufactured product. Chemical maps were obtained by Raman mapping and elemental maps by scanning electron microscopy with energy-dispersive X-ray spectroscopy. Large variations in both tablet weights and breaking forces were observed in all tested samples, resulting in significant quality complications. It was suspected that the API tended to adhere to the process equipment, accounting for the low API content in the powder mixture and tablets. These results suggest that this API or the tablet composition was unsuitable for manufacturing in a continuous line; further testing could be continued with different materials and changes in the process.
V práci byl studován vliv typu rozvolňovadla a kluzné látky na destrukční teplo tabletovin a tablet.Destrukční teplo bylo zjišťováno izoperibolickou kalorimetrií. Tabletoviny a tablety obsahovaly jakosuché pojivo Avicel PH 101, jako rozvolňovadla 10% Primojelu, Ac-Di-Solu nebo Polyplasdone XLa jako kluzné látky 5% stearanu hořečnatého nebo laurylsíranu sodného. Součet destrukčních tepeljednotlivých pomocných látek se rovnal zjištěným hodnotám v tabletovinách a tabletách. Oprotitabletovinám byly u tablet zjištěny vyšší hodnoty destrukčních tepel o 57,9 %. U testovanýchrozvolňovadel a kluzných látek byly zjištěné hodnoty destrukčních tepel závislé na hodnotáchdestrukčních tepel jednotlivých pomocných látek. U rozvolňovadel byla zjištěna lineární závislostcelkového destrukčního tepla (CDT) na destrukčním teple rozvolňovadel (DTR ), daná vztahemCDT = 0,797.DTR + 17,666 při korelačním koeficientu r = 0,986.
The paper studies the effect of the type of the disintegrating substance and the lubricant on thedestruction heat of tablet materials and tablets. Destruction heat was determined by means ofisoperibolic calorimetry. Tablet materials and tablets contained Avicel PH 101 as the dry binder,10% of Primojel, Ac-Di-Sol, or Polyplasdone XL as disintegrating substances, and 5% of magnesiumstrearate or sodium laurylsulfate as the lubricants. The sum of destruction heats of the individualauxiliary substances equalled the found values in tablet materials and tablets. In tablets, in contrastto tablet materials, values of destruction heat higher by 57.9 % were found. In the disintegratingsubstances and lubricants tested, the found values of destruction heats were dependent on the valuesof destruction heats of the individual auxiliary substances. In the disintegrating substances, a lineardependence of the total destruction heat (CDT) on the destruction heat of the disintegratingsubstances (DTR) was found, given by the relationship CDT = 0.797.DTR + 17.666 with thecorrelation coefficient r = 0.986.
- Klíčová slova
- AVICEL PH 101, PRIMOJEL, AC-DI-SOL, POLYPLASDONE XL,
- MeSH
- farmaceutické pomocné látky chemie MeSH
- finanční podpora výzkumu jako téma MeSH
- kalorimetrie normy MeSH
- lékové formy analýza MeSH
- rozpustnost MeSH
- tablety analýza chemie MeSH
- Publikační typ
- srovnávací studie MeSH
The aim of this systematic study was to analyze the granulometric and rheological behavior of tableting mixtures in relation to tabletability by single tablet and lab-scale batch compression with an eccentric tablet machine. Three mixtures containing 33, 50, and 66% of the cohesive drug paracetamol were prepared. The high compressibility of the powder mixtures caused problems with overcompaction or lamination in the single tablet compression method; due to jamming of the material during the filling of the die, the lab-scale batch compression was impossible. Using high shear granulation, the flow properties and tabletability were adjusted. A linear relationship between the span of granules and the specific energy measured by FT4 powder rheometer was detected. In parallel, a linear relationship between conditioned bulk density and the tensile strength of the tablets at lab-scale batch tableting was noted. The combination of dynamic image analysis and powder rheometry was useful for predicting the tabletability of pharmaceutical mixtures during the single tablet (design) compression and the lab-scale batch compression.
