The effect of powder blend and tablet structure on drug release mechanisms of hydrophobic starch acetate matrix tablets.

This study investigates the release mechanism of a hydrophilic drug (caffeine) from hydrophobic matrix tablets composed of starch acetate. Different particle size fractions of starch acetate were mixed with caffeine (22% V/V) to obtain various mixture organisations in the powder, as well as in the final tablet. The organisation of powder mixtures was calculated by the carrier payload of starch acetate particles, while the pore size distributions in tablets were measured by mercury intrusion porosimetry. A carrier payload below 1 indicated the existence of a free starch acetate particle surface, while numbers greater than 1 pointed to a complete occupation of the starch acetate particle surface area by caffeine particles. The carrier payload calculations gave a good prediction for the existence of a starch acetate matrix in the tablet structures. Caffeine matrices in tablets compressed from the mixtures could be detected by mercury intrusion porosimetry measurements. The existence of different matrices, as well as different pore networks, determined the physical changes of the tablets and the release mechanism of caffeine during dissolution tests. When a tablet contained only a caffeine matrix, rapid tablet disintegration and immediate release of the total amount of caffeine occurred. A single matrix of starch acetate resulted in tablets that remained intact, although cracks were formed. The co-existence of matrices of both materials created surface erosion of the tablet. The caffeine release profiles of tablets that remained intact or showed erosion were fitted by an equation containing both diffusional and relaxational factors to describe the effect of tablet porosity on drug release.

Compaction mechanism and tablet strength of unlubricated and lubricated (silicified) microcrystalline cellulose.

This paper describes the differences in compaction properties between microcrystalline cellulose (MCC) and microcrystalline cellulose co-processed with colloidal silicon dioxide (SMCC). The different compaction parameters are not only compared for the pure materials, but also for the lubricated powders with magnesium stearate. Neither magnesium stearate, nor colloidal silicon dioxide, facilitates extensively the densification of (silicified) microcrystalline cellulose during compaction. The difference in tablet relaxation of MCC and SMCC indicates a small negative effect of colloidal silicon dioxide on the interparticle bonding strength of unlubricated MCC. However, for lubricated MCC a larger increase in tablet relaxation at a high compression speed was found than for lubricated SMCC tablets. Accordingly, the decrease in tablet strength was larger for the MCC tablets than for the SMCC tablets when lubrication was applied. The examination of the tablet strengths of tablets compressed from physical mixtures of MCC with increasing concentrations of colloidal silicon dioxide proved the slightly negative influence of silicon dioxide on the tablet strength of unlubricated MCC tablets and the positive effect of colloidal silicon dioxide addition on the tensile strength of lubricated MCC tablets. Co-processing of MCC with colloidal silicon dioxide showed no extra contribution on the tablet strength of lubricated tablets above the physical mixtures. The interactions between the different materials were further supported by the interaction parameters based on partial solubility parameters.

The influence of particles of a minor component on the matrix strength of sodium chloride.

This paper deals with the matrix strength of sodium chloride particles in pure sodium chloride tablets and in tablets compressed from binary mixtures of sodium chloride with low concentrations of pregelatinised starch. Because this study concerns the strength of the sodium chloride matrix, the tablet strength is reflected as a function of the sodium chloride volume fraction in the tablet. Starch particles in the mixture tablets decrease the sodium chloride volume fraction-tensile strength relationship compared with that of pure sodium chloride tablets. To determine the contribution of the sodium chloride matrix to the tablet strength, the starch particles were removed from the mixture tablets by heat treatment. Determination of the strengths of these heat-treated tablets reveals that the sodium chloride matrix strength determines the tablet strength of mixture tablets containing a single matrix of sodium chloride particles. The decrease of the sodium chloride matrix density in the three different tablets (pure sodium chloride tablets, mixture tablets and heat-treated tablets) is reflected by an increase of the median pore size. The matrix in sodium chloride tablets shows a higher tensile strength to median pore size relation than the matrices in the mixture and heat-treated tablets. Based on calculations according to the theory of elastic-brittle fracture, it is suggested that the initial presence of starch particles during tablet compaction causes the pores in the matrices of the mixtures and heat-treated tablets to be relatively more flat and longer. These pores weaken the sodium chloride matrix in the mixture and heat-treated tablets to a larger extent than the shorter, more spherical pores formed during compaction of pure sodium chloride.

Pore formation in tablets compressed from binary mixtures as a result of deformation and relaxation of particles.

This paper describes the internal structure of tablets compressed from binary mixtures of sodium chloride and pregelatinised starch. The minimum particle diameter of pregelatinised starch inside tablets compressed from mixtures was calculated from the difference between the initial pore size distribution and the pore size distribution after removal of the starch particles by burning. Subsequently, the tablets were carefully crushed. These powders, consisting of almost only sodium chloride particles, were measured by laser diffraction. It was found that the diameter of the sodium chloride particles hardly changed, whereas the minimum diameter of starch particles strongly decreased during the compaction process. As an effect of the difference in yield pressure, the harder sodium chloride particles cause deformation of the softer starch particles, resulting in a change in particle shape. The pore size distribution of tablets compressed from mixtures of sodium chloride and starch is typically that of viscoelastic materials; the larger pores (>5 microm) change, while the small pores stay constant in number and size. The median pore diameter in tablets compressed from the mixtures is higher than the median pore diameter in tablets compressed from the pure materials. This paper shows that the formation of large pores was the result of the extra porosity expansion of tablets compressed from binary mixtures of sodium chloride and pregelatinised starch.

Tensile strength of tablets containing two materials with a different compaction behaviour.

The tensile strength of tablets compressed from binary mixtures is in general not linearly related to the strength of tablets prepared from single materials; in many cases it shows a decreased tensile strength relative to interpolation. The materials used in this study, sodium chloride and pregelatinised starch, are both plastically deforming materials, but have a different densification and relaxation behaviour. The yield pressure of the binary mixtures shows an almost linear relationship. As an effect of their lower yield pressure, starch particles yield earlier than sodium chloride particles. The following enclosure prevents some sodium chloride particles to yield or crack. The relaxation of the tablets is higher than the relaxation calculated by linear interpolation of the relaxation behaviour of the two pure materials. The difference between the measured porosity expansion and the data obtained by linear interpolation can be considered as a measure for the reduced interparticle bonding. SEM-photographs indicate that the reduced interparticle bonding is caused by the low adhesive forces. The measured decrease of the tensile strength of the tablets is also considered to be the result of reduced interparticle bonding. In this paper it is shown that there exists a similar relationship between the tensile strength reduction and the percentage of starch on the one hand and the extra porosity expansion and the starch percentage on the other hand.

Effect of magnesium stearate on bonding and porosity expansion of tablets produced from materials with different consolidation properties.

The negative effect of magnesium stearate on tablet strength is widely known. This strength reduction is always considered to be the result of reduction of interparticle bonding. It is also known that interparticle bonding affects relaxation of tablets. Relaxation increases with decreasing bonding. Microcrystalline cellulose is an example of a material with a high lubricant sensitivity, which effect is caused by its plastic deformation behavior during compression. This paper shows for microcrystalline cellulose that the porosity under pressure was equal for unlubricated tablets and for tablets containing 0.5% magnesium stearate. This points to equal densification properties. The lubricated tablets show, however, a much larger relaxation than the tablets without magnesium stearate. This difference can be ascribed to the reduction of interparticle bonding by the lubricant, because a strong interparticle bonding counteracts tablet relaxation. In contrast to microcrystalline cellulose, aggregated gamma-sorbitol (Karion Instant) has a low lubricant sensitivity. Both porosity under pressure and tablet relaxation were found to be equal for lubricated and unlubricated sorbitol tablets. This phenomenon is caused by the particle structure of gamma-sorbitol. During compression, a lubricant film will be destroyed by fragmentation of the sorbitol aggregates. For this reason, magnesium stearate will hardly affect the interparticle bonding between sorbitol particles and hence have only a small or no effect on tablet relaxation.

Effect of compaction temperature on consolidation of amorphous copolymers with different glass transition temperatures.

PURPOSE: The purpose of this study was to relate the combination of glass transition temperature (Tg) and temperature of measurement with the mechanical and compaction properties of some test materials. METHODS: Copolymers with different Tg'S were synthesised by free radical copolymerisation of methyl methacrylate with lauryl methacrylate. Elastic moduli were measured by dynamic mechanical analysis at different strain rates and temperatures. Compaction experiments were performed at different compaction speeds and temperatures. RESULTS: The difference between temperature of measurement and Tg appears to determine both elastic modulus and yield strength completely. They both decrease with decreasing difference between temperature of measurement and Tg and increase with strain rate. At temperatures of measurement higher than the Tg the elastic modulus is extremely low because the materials behave as rubbers. Consequently, the amount of energy stored during compaction decreases when the compaction temperature approaches the Tg and increases with strain rate. When the compaction temperature is higher than the Tg, the amount of stored energy is extremely large. The compaction experiments show that the final tablet porosity is completely determined by stress relaxation phenomena. Consequently, the final tablet porosity follows exactly the same relation as that of stored energy. CONCLUSIONS: The final tablet porosity is unequivocally determined by the amount of stored energy. This implies that tablet production at a temperature of about 20 K under the glass transition temperature of the material yields tablets with minimum porosity.

Effect of dehydration on the binding capacity of particulate hydrates.

The binding capacities of alpha-D-glucose dehydrated at temperatures from 60-135 degrees C increased with increasing temperature of dehydration.

In vitro and in vivo availability of hydrophilized phenytoin from capsules.

The effect of phenytoin hydrophilization on the liquid penetration rate into prepared plugs, on the disintegration time, on the in vitro release rate, and on in vivo absorption in humans was studied. Hydrophilization was performed by intensive mixing of the hydrophobic drug with a small amount of methylcellulose solution. Liquid penetration into the treated plugs was independent of the liquid wetting potency and extremely high compared to the pure drug plugs. Analogous results were obtained for the disintegration time and in vitro release rates from capsules loaded with pure and treated drug. A bioavailability study in seven healthy volunteers showed immediate absorption of the treated drug but a 1-hr absorption lag time for the pure drug.