Comparison of ibuprofen release from minitablets and capsules containing ibuprofen: β-Cyclodextrin complex

NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Pharmaceutics and Biopharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Eur J Pharm Biopharm. 2011 May;78(1):58-66. Epub 2010 Dec 30.Mixtures containing ibuprofen (IB) complexed with b-cyclodextrin (bCD) obtained by two complexation methods [suspension/solution (with water removed by air stream, spray- and freeze-drying) and kneading technique] were processed into pharmaceutical dosage forms (minitablets and capsules). Powders (IB, bCD and IBbCD) were characterized for moisture content, densities (true and bulk), angle of repose and Carr’s index, X-ray and NMR. From physical mixtures and IBbCD complexes without other excipients were prepared 2.5-mm-diameter minitablets and capsules. Minitablets were characterized for the energy of compaction, tensile strength, friability, density and IB release (at pH 1.0 and 7.2), whereby capsules were characterized for IB release. The results from the release of IB were analyzed using different parameters, namely, the similarity factor (f2), the dissolution efficiency (DE) and the amounts released at a certain time (30, 60 and 180 min) and compared statistically (a = 0.05). The release of IB from the minitablets showed no dependency on the amount of water used in the formation of the complexes. Differences were due to the compaction force used or the presence of a shell for the capsules. The differences observed were mostly due to the characteristics of the particles (dependent on the method considered on the formation of the complexes) and neither to the dosage form nor to the complex of the IB

Mechanics and Computational Modeling of Pharmaceutical Tabletting Process

Reference Module in Materials Science and Materials EngineeringPharmaceutical Manufacturing Technology Centre (PMTC) in Irelan

Effect of temperature increase during the tableting of pharmaceutical materials

Scale-up of tableting process is particularly difficult due to specific concerns related exclusively to the process itself and that cannot be determined on a smaller scale, which are the effect of compression speed and the build-up of heat due to the length of the compaction operations. In this work, it has been simulated the rise of temperature observed during the tablets manufacturing in a full production scale by means of an appropriate modification of a R&D rotary tablet machine. Four common pharmaceutical excipients, characterized by different chemical nature, consolidation behaviour and temperature sensitiveness have been analysed in terms of compaction mechanism (Heckel and energy analysis) and tabletability, in order to verify any effect of the increase of temperature. The results showed a relevance of the temperature on mechanical tablets properties only on materials characterized by low temperature thermal transitions (melting or glass transition), while, for compounds which do not exhibit thermal events at low temperature, it becomes less important for ductile materials and irrelevant for brittle materials. Heckel analysis highlighted a noticeable increase of ductility only in those materials whose tablets mechanical properties depended on the temperature. On the other hand, energy analysis showed low sensitivity failing to identify any temperature effect on compaction materials properties. This work showed how to simulate the process of temperature rise on a small scale and the influence of temperature on materials compaction properties. The use of a modified tableting machine, able to control the temperature and moisture levels and also capable of monitoring the punch movements, resulted in identifying the effect of temperature both on mechanical and compaction properties on materials. Thus, it represents a valuable tool in order to provide useful information at an early stage during the development of tablets formulations

Study on the Recovery of Post-Compaction Matrices

Ph.DDOCTOR OF PHILOSOPH

Structure Pharmaceutics Based on Synchrotron Radiation X-Ray Micro- Computed Tomography: From Characterization to Evaluation and Innovation of Pharmaceutical Structures

Drug delivery systems (DDS) are essentially pharmaceutical products for human therapy, typically involving a mixture of active ingredients and excipients. Based upon quantitative characterization of structure, the thesis introduces the concept of classifying the architecture of DDS into four levels by their spatial scale and the life time period. The primary level is recognised as the static structure of the whole dosage form with a size from μm to cm with the final structure generated by formulation design. The secondary level categorises the structures of particles or sub-units to form a DDS with sizes from nm to mm as key units in processing such as mixing, grinding, granulation and packing; The tertiary level represents the dynamic structures of DDS during the drug release phase in vitro or in vivo incorporating the structure size range from nm to mm, which undergo changes during dissolution, swelling, erosion or diffusion. The spatial scale for the quaternary level is defined as the meso or micro scale architecture of active and non-active molecules within a DDS with sizes from Å to μm for the molecular structure of drug and excipients. Methods combining X-ray tomography, image processing, and 3D reconstructions have been devised and evaluated to study systematically pharmaceutical structures and correlate them with drug release kinetics of DDS. Based on the quantitative structural information of pharmaceutical intermediates and dosage forms, it is possible now to correlate structures with production processing, behaviour and function, and the static and dynamic structures of DDS with the release kinetics. Thus, a structure-guided methodology has been established for the research of DDS.Chinese Academy of Science

INJECTION MOLDING/MICROMOLDING APPLICATIONS TO DRUG DELIVERY

In the present work the application potential of injection molding (IM) and micromolding (\ub5IM) for the manufacturing of drug products was investigated. These techniques are largely employed in the plastics industry to process thermoplastic polymers into objects with different size, shape and possibly many details, and they could offer several advantages in the pharmaceutical area, mainly related to versatility, patentability, scalability and production costs (continuous manufacturing). Processes and equipment generally employed as well as current pharmaceutical applications already proposed in the literature were preliminarily reviewed. Drug delivery systems (DDSs) in the form of gastro-resistant containers based on HPMCAS were afterwards designed and manufactured by \ub5IM. Notably, such DDSs represent a step forward in the field as they may provide a ready-to-use alternative to enteric-coated dosage forms. Moreover, the feasibility by hot-processing techniques (hot melt extrusion and IM) of prolonged-release hydrophilic matrices and immediate release tablets was demonstrated, which could help promoting the use of continuous manufacturing in the pharmaceutical production areas

Compaction analysis and optimisation of convex-faced pharmaceutical tablets using numerical techniques

Capping failure, edge chipping, and non-uniform mechanical properties of convexfaced pharmaceutical tablets are common problems in pharma industry. In this paper, Finite Element Modelling (FEM) and Design of Experiment (DoE) techniques are adopted to find the optimal shape of convex-faced (CF) pharmaceutical tablet which has more uniform mechanical properties and less capping and chipping tendency. The effects of the geometrical parameters and friction on the compaction responses of convex-faced pharmaceutical tablets were first identified and analysed. The finite element model of the tabletting process was generated using the implicit code (ABAQUS) and validated against experimental measurements. Response Surface Methodology (RSM) was employed to establish the relationship between the design variables, represented by the geometrical parameters and the friction coefficient, and compaction responses of interest including residual die pressure, the variation of relative density within the tablet, and the relative shear stress of the edge of the tablet. A statistical-based optimisation approach is then employed to undertake shape optimisation of CF tablets. The obtained results demonstrated how the geometrical parameters of CF tablet and the friction coefficient have significant effects on the compaction behaviour and quality of the pharmaceutical tablet