Freeze-dried pregelatinized Dioscorea starches as tablet matrix for sustained release

Freeze dried pregelatinized Dioscorea starches have been evaluated as a directly compressible excipient for sustained release using diclofenac sodium and caffeine as the model drugs. The tableting and tablet properties of the binary and ternary mixtures of the drug/starch/excpients were assessed using the 3-D modeling parameters and the crushing force of the tablets while the drug release properties were also evaluated. The effect of dicalcium phosphate dihydrate on the compaction and drug release properties of the matrices was also investigated. The results obtained indicate the tablet formation properties of the starches depend on the Dioscorea starch used and on the concentration of drug present in the matrix tablets. There appears to be a decrease in the CF of the tablets as the concentration of drug in the matrix is increased. Inclusion of dicalcium phosphate dihydrate in the tablet matrix increased the bonding in the matrix tablets leading to an increase in CF of the tablets. The amount for drug release from the matrices, and the release rates and mechanism were also dependent on the Dioscorea starch used and the drug concentration. Modified Bitter matrices provided a controlled release of diclofenac for up to 5 hours while modified Chinese starches provided controlled release for over 24 hours. The release mechanism from modified Chinese matrices was found to be Super Case-II transport or time-independent release kinetics. Furthermore, the release rates were dependent on the concentration of the drug present in the matrix. Thus, the modified starch matrices could be used to achieve different drug release profiles depending on the intended use of the tablets. The addition of dicalcium phosphate dihydrate not only improved the mechanical properties of the tablets but also altered the release rates and kinetics. Thus, modified Chinese and Bitter could find application as excipient for controlled drug delivery

The pressure-volume-temperature relationship of cellulose

Pressure–volume–temperature (PVT) mea- surements of a-cellulose with different water contents, were performed at temperatures from 25 to 180 °C and pressures from 19.6 to 196 MPa. PVT measurements allowed observation of the combined effects of pressure and temperature on the specific volume during cellulose thermo-compression. All isobars showed a decrease in cellulose specific volume with temperature. This densification is associated with a transition process of the cellulose, occurring at a temperature defined by the inflection point Tt of the isobar curve. Tt decreases from 110 to 40 °C with pressure and is lower as moisture content increases. For isobars obtained at high pressures and high moisture contents, after attaining a minimum, an increase in volume is observed with temperature that may be related to free water evaporation. PVT a-cellulose experimental data was compared with predicted values from a regression analysis of the Tait equations of state, usually applied to synthetic polymers. Good correla- tions were observed at low temperatures and low pressures. The densification observed from the PVT experimental data, at a temperature that decreases with pressure, could result from a sintering phenomenon, but more research is needed to actually understand the cohesion mechanism under these conditions

Use of 3-D modeling in the early development phase of pectin tablets

This study examines the contribution of a 3-D model in an early development of pectin tablets. The aim of this work was to extract as much information of the compression behavior from as few tablets as possible. Pectins with various degrees of methoxylation (DM) were studied (4%-72%). The compressibility was evaluated using classic “in-die” Heckel and Kawakita analyses in addition to the 3-D modeling. For validation purposes well-known reference materials were included. 3-D modeling applied to data of single tablets yielded some information on their compressibility. When several tablets with different maximum relative densities were included, no additional information was obtained through classic evaluation. However, the 3-D model provided additional information through the shape of the 3-D parameter plot. Pectins with a DM >= 25% consolidated predominantly by elastic deformation similarly to the 3-D parameter plot of pregelatinized starch (PGS). The 3-D analysis also suggests some degree of fragmentation and, for some of the low-methoxylated pectins (DM <= 10%), viscoelastic deformation. This study showed that by applying 3-D modeling it is possible to differentiate between elastic and viscoelastic materials for tablets with different relative density values

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Powder Compaction: Compression Properties of Cellulose Ethers

Effective development of matrix tablets requires a comprehensive understanding of different raw material attributes and their impact on process parameters. Cellulose ethers (CE) are the most commonly used pharmaceutical excipients in the fabrication of hydrophilic matrices. The innate good compression and binding properties of CE enable matrices to be prepared using economical direct compression (DC) techniques. However, DC is sensitive to raw material attributes, thus, impacting the compaction process. This article critically reviews prior knowledge on the mechanism of powder compaction and the compression properties of cellulose ethers, giving timely insight into new developments in this field