Continuous direct tablet compression: effects of impeller rotation rate,total feed rate and drug content on the tablet properties and drug release

Context: Continuous processing is becoming popular in the pharmaceutical industry for its cost and quality advantages.

Objective: This study evaluated the mechanical properties, uniformity of dosage units and drug release from the tablets prepared by continuous direct compression process.

Materials and methods: The tablet formulations consisted of acetaminophen (3–30% (w/w)) pre-blended with 0.25% (w/w) colloidal silicon dioxide, microcrystalline cellulose (69–96% (w/w)) and magnesium stearate (1% (w/w)). The continuous tableting line consisted of three loss-in-weight feeders and a convective continuous mixer and a rotary tablet press. The process continued for 8?min and steady state was reached within 5?min. The effects of acetaminophen content, impeller rotation rate (39–254?rpm) and total feed rate (15 and 20?kg/h) on tablet properties were examined.

Results and discussion: All the tablets complied with the friability requirements of European Pharmacopoeia and rapidly released acetaminophen. However, the relative standard deviation of acetaminophen content (10% (w/w)) increased with an increase in impeller rotation rate at a constant total feed rate (20?kg/h). A compression force of 12?kN tended to result in greater tablet hardness and subsequently a slower initial acetaminophen release from tablets when compared with those made with the compression force of about 8?kN.

Conclusions: In conclusion, tablets could be successfully prepared by a continuous direct compression process and process conditions affected to some extent tablet properties.     

The influence of the concentration: Variable diffusivity on the mass transfer from a polymer into a liquid

The unsteady, conjugate, mass transfer of the packaging constituents to a food product has been analysed. The system was considered motionless (hydrostatic conditions). The diffusion coefficient inside the packaging material was considered concentration variable while the diffusion coefficient inside the food product was considered constant. The mass balance equations were solved numerically. The influence of the concentration‐variable diffusivity on the mass transfer mechanism and rate was analysed for different values of the partition coefficient and packaging thickness.     

Comparison of two paddle wheel geometries within the filling chamber of a rotary tablet press feed frame with regard to the distribution behavior of a model powder and the influence on the resulting tablet mass

Objective: The purpose of this study was to compare the influence of two different paddle wheel geometries on the distribution behavior of a model powder within the filling chamber of the modified feed frame of a rotary tablet press. Moreover, both paddle wheels were compared regarding their influence on the resulting tablet mass during the tableting process.

Significance: Insights are provided regarding the influence of the paddle wheel geometry on the powder distribution to optimize the die filling process.

Materials and methods: Avicel PH 102 served as model powder. A laser triangulator was used to scan the powder surface level within the feed frame and, combined with the determination of the angle position of the paddle wheel, an in-house written software was used to calculate the powder surface profiles and filling levels. Two experimental setups, one based on the filling chamber filled with a defined amount of powder (offline) and one using the filling chamber during tableting (inline) were applied.

Results: Both paddle wheel geometries caused a significantly different distribution behavior of the powder within the filling chamber. The tablets obtained with the round rod filling wheel showed significantly higher tablet masses and significantly lower standard deviations. The inflow of powder into the filling chamber appeared to be improved with the round rod filling wheel.

Conclusions: Under the applied experimental conditions, the round rod filling wheel showed obvious advantages compared to that with flat rods in terms of the uniformity of tablet masses and the extent of die filling.     

A quality-by-design study to develop Nifedipine nanosuspension: examining the relative impact of formulation variables,wet media milling process parameters and excipient variability on drug product quality attributes

Abstract

Wet milling is a multifunctional and the most common method to prepare a drug nanosuspension for improving the bioavailability of poorly water soluble drugs. A suitable way of preparing a high drug-loaded nifedipine nanosuspension using wet stirred media milling was investigated in the present study. Nifedipine, a poorly water soluble drug, was selected as a model drug to enhance its dissolution rate and oral bioavailability by preparing an appropriate crystalline nanosuspension. Process parameters, such as milling media volume, milling speed and milling time, were optimized using the one variable at a time (OVAT) approach. A similar method was used to select an appropriate polymeric stabilizer and a surfactant from different categories of polymeric stabilizers (HPC SL, HPC SSL Soluplus®, Kollidon^® VA 64 and HPMC E 15) and surfactants (Poloxamer 407, Kolliphor TPGS and Docusate sodium). A systematic optimization of critical formulation parameters (such as drug concentration, polymer concentration and surfactant concentration) was performed with the aid of the Box-Behnken design. Mean particle size, polydispersity index and zeta potential as critical quality attributes (CQAs) were selected in the design for the evaluation and optimization of the formulation and validation of the improved product. The nifedipine nanosuspension that was prepared using HPC and poloxamer 407 was found to be most stable with the lowest mean particle size as compared with the formulations prepared using other polymeric stabilizers and surfactants. The optimized formulation was further spray-dried and characterized using the Fourier Transform Infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), polarized light microscopy (PLM) and in-vitro dissolution study. Results have shown no interaction between the drug particles and stabilizers, nor a reduction in the crystallinity of drug, nor an increase in the saturation solubility and rapid in vitro dissolution as compared with pure nifedipine crystals. Thus, the current study supports the suitability of the wet stirred media milling method and a combination of HPC SSL and poloxamer 407 as stabilizers for the preparation of nifedipine nanosuspension.     

The compression/absorption cycle – influence of some major parameters on COP and a comparison with the compression cycleLe cycle à compression–absorption: influence de certains paramètres importants sur le COP et comparaison avec le cycle à compression

This article concerns two main studies: a parameter study and a comparison. In the parameter study, the CAHP is focused upon. Its COP sensitivity to changes in the absorber and desorber falling-film tube length, heat exchanger area distribution, and concentration change of the solution in the absorber is studied. The relative distribution between the desorber and absorber is found to have little impact on COP. The area distributed to the solution heat exchanger and the concentration change in the absorber is found to have a large impact on COP when examined separately, but when they are studied together, and with optimized concentration change for each area distribution, the total impact is low. It is shown that the falling-film tubes should be designed to be as long as possible in order to increase the COP.The comparison involves a new procedure for comparing the performance (COP) of a compression/absorption heat pump (CAHP) with that of a compression heat pump (CHP). In the procedure local heat transfer coefficients and pressure drop are taken into account. Further, the comparison is performed for various heating applications and with specified investment level. The heating applications are typically industrial or district heating cases and are chosen to study impact of three different kinds: size of the sink and source temperature change (glide), temperature lift for a given sink and source glide and temperature level for a given sink and source glide. Ammonia/water is used as working fluid in the CAHP and isobutane in the CHP. A relevant industrial design is assumed for the CHP (including an indirect economizer coupling, suction gas heat exchanger, sub-cooler and surface enhancements in evaporator and condenser), which is not the case in previous comparisons of this type. The absorber and desorber in the CAHP are modeled as vertical falling-film tube-and-shell heat exchangers. The main results for the comparison study are: (1) the COP of the CAHP is as good as that of the CHP when the sink and source glides are 10 K; (2) when the glide of the sink and source is increased to 20 K, the CAHP has a 12% better performance than the CHP; and (3) an increased temperature lift and an increased temperature level give the CAHP a relatively worse COP. Some COP-increasing design parameters to be studied further are proposed for the CAHP.