Biomedical subjects

E I Keleb

Publications and source records attributed to E I Keleb.

6 recordsLinked to original sources

PubMed2005

Tablets prepared by single-step granulation/tabletting: interparticulate binding mechanism and stability.

The binding mechanism of tablets prepared by single-step granulation/tabletting (SSGT), a novel technique for the production of tablets, was evaluated. SSGT yielded hard tablets having a short disintegration time due to their porous, spongelike internal structure. Calculation of the interaction factor and electrical conductance tests confirmed the presence of solid bridges that provided a higher tensile strength to these compacts in comparison to tablets prepared by conventional tabletting techniques. At high relative humidity, moisture sorption and glass-to-rubber transition of the binder (polyvinylpyrrolidone), or condensation of moisture on the internal pore surface, reduced the tensile strength of the SSGT-manufactured tablets. Contrary to tablets prepared by granulation and compression, the SSGT tablets did not harden during storage under conditions of varying relative humidity (alternating the relative humidity every 24 hr between 33% and 75%).

Drug Stability↗

PubMed2004

Twin screw granulation as a simple and efficient tool for continuous wet granulation.

The modification of a twin screw extruder for continuous wet granulation was investigated. Modification of the extruder setup as well as the screw design allowed the continuous wet granulation of alpha-lactose monohydrate without the need of a wet sieving step. The robustness of twin screw granulation was evaluated by studying the influence of processing parameters and formulation variables on the process performance and on the properties of alpha-lactose monohydrate granules and tablets. The process reproducibility during long term production was evaluated. Screw speed (200-450 rpm) and total input rate (5.5-9.5 kg/h) had no significant influence on the granule properties, while the water concentration during granulation influenced the process as well as the granule properties. At a water concentration (calculated on wet granule basis) of 5.5-8.5%, continuous twin screw granulation of alpha-lactose monohydrate 200 M was feasible and the granules obtained had good properties. PVP addition mainly affected tablet properties. Tablets made from granules containing 2.5% PVP had a tensile strength above 0.94 MPa, a friability below 1% and a disintegration time ranging between 495 and 576 s. Tablets containing hydrochlorothiazide complied with the dissolution requirements as 60% was released after 5 and 15 min from tablets without PVP and with 2.5% PVP, respectively. No problems were observed during continuous twin screw granulation over a period of 8h and the granule and tablet properties were reproducible throughout the process. These results indicated that twin screw granulation is an efficient tool for continuous wet granulation.

Excipients↗

PubMed2004

Single-step granulation/tabletting of different grades of lactose: a comparison with high shear granulation and compression.

The influence of the particle size, particle morphology and crystallinity of lactose on the extrusion properties and on the quality of tablets were investigated using single-step granulation/tabletting as a tabletting technique. Results showed that particle size and type of lactose (alpha-lactose monohydrate, anhydrous beta-lactose and spray dried lactose) affected the powder feeding, the process performance as well as the process capacity. Different grades of lactose yielded tablets with similar tensile strength, but significantly different disintegration time. Single-step granulation/tabletting always yielded tablets with a significantly higher tensile strength and similar or significantly lower disintegration time compared to high shear granulation and compression. The tensile strength of alpha-lactose monohydrate tablets (without and with PVP) did not change during one year of storage at 60% RH-25 degrees C and at 75% RH-40 degrees C, whereas a significant increase in disintegration time was observed. It can be concluded that although the lactose grade affected the performance and the optimal parameters of single-step granulation/tabletting, all lactose grades can be efficiently processed using this technique.

Compressive Strength↗

PubMed2004

Extrusion granulation and high shear granulation of different grades of lactose and highly dosed drugs: a comparative study.

Formulations containing different lactose grades, paracetamol, and cimetidine were granulated by extrusion granulation and high shear granulation. Granules were evaluated for yield, friability, and compressibility. Tablets were prepared from those granules and evaluated for tensile strength, friability, disintegration time, and dissolution. The different lactose grades had an important effect on the extrusion granulation process. Particle size and morphology affected powder feeding and power consumption, but had only a minor influence on the granule and tablet properties obtained by extrusion granulation. In contrast, the lactose grades had a major influence on the granule properties obtained by high shear granulation. Addition of polyvinylpyrrolidone (PVP) was required to process pure paracetamol and cimetidine by high shear granulation, whereas it was feasible to granulate these drugs without PVP by extrusion granulation. Granules prepared by extrusion granulation exhibited a higher yield and a lower friability than those produced by high shear granulation. Paracetamol and cimetidine tablets compressed from granules prepared by extrusion granulation showed a higher tensile strength, lower friability, and lower disintegration time than those prepared from granules produced by high shear granulation. Paracetamol tablets obtained via extrusion granulation exhibited faster dissolution than those obtained via high shear granulation. For all lactose grades studied, extrusion granulation resulted in superior granule and tablet properties in comparison with those obtained by high shear granulation. These results indicate that extrusion granulation is more efficient than high shear granulation.

Acetaminophen↗

PubMed2002

Continuous twin screw extrusion for the wet granulation of lactose.

The suitability of continuous twin screw extrusion for the wet granulation of alpha-lactose monohydrate was studied and compared with conventional high shear granulation. The influence of process parameters (screw speed and total input rate) and formulation variables (water and polyvinylpyrrolidone (PVP) concentration) on the properties of granules (yield, particle size distribution, friability and compressibility) and tablets (tablet tensile strength, friability and disintegration time) was investigated. Variation of the formulation and process parameters had a major effect on the process feasibility. Optimization of these parameters is required to allow continuous processing and to ensure a high yield. Total input rate, screw speed and water concentration had a minor influence on the granule and the tablet properties. The addition of PVP had no major influence on the granule properties, but significantly affected the tablet characteristics. For granules formulated with and without PVP a yield above 50%, a friability below 30% and a compressibility below 15% was obtained. Tablets without PVP showed a tensile strength below 0.6 MPa, a friability above 1% and a disintegration time below 3 min, whereas tablets with PVP showed a tensile strength above 0.6 MPa, a friability below 1% and a disintegration time ranging from 8 to 15 min. High shear granulation was only possible when PVP was added and it required a higher amount of water. It was concluded that wet granulation of alpha-lactose monohydrate using continuous twin screw extrusion is a robust process and might offer a suitable alternative for high shear granulation in the pharmaceutical industry.

Algorithms↗

PubMed2001

Cold extrusion as a continuous single-step granulation and tabletting process.

The potential of cold extrusion as a continuous granulation/tabletting technique was investigated. Extrudates (X, 9 mm) were produced using twin-screw extrusion, cut manually into tablets (thickness, 4 mm) and dried at 25 degrees C for 20 h. alpha-Lactose monohydrate (200 M) was used as an excipient, PVP (Kollidon K30) and water as binders, and hydrochlorothiazide as the model drug. The influence of formulation (water content, PVP addition, drug incorporation) and process (total input rate and screw speed) parameters on the process (torque, die pressure, visual evaluation of tablets) and on the tablet properties (tensile strength, friability, disintegration time, porosity) was evaluated. Formulation, as well as process parameters, affected the process feasibility, but had only a minor effect on the tablet properties at conditions that allowed continuous tablet production. All alpha-lactose monohydrate tablets formulated without and with PVP and produced at optimum conditions showed tensile strengths above 0.7 and 1.5 MPa, friabilities below 1.0 and 0.9%, and disintegration times below 1 and 8 min, respectively. This technique allows single-step granulation/tabletting of pure alpha-lactose monohydrate, indicating that cold extrusion could be used as alternative tablet production technique for ingredients with poor compaction properties. As the tablets prepared by extrusion have a much higher porosity compared with conventional tablets, this technique could also be useful for tablet production of formulations with poor disintegrating properties.

Chemistry, Pharmaceutical↗