Nobuyuki Kitamori

Effect of Mixing Time on the Lubricating Properties of Magnesium Stearate and the Final Characteristics of the Compressed Tablets

AbstractThe effect of mixing time on hardness, disintegration time and ejection force in tablettlng of magnesium stearate and lactose granules was studied. The hardness of the tablets decreased with an increase in mixing time of the blends, as previously reported. A semilogarithmic plot of the hardness versus mixing time gave a straight line having a turning point. At the early phase of mixing the hardness was decreasing with a large first-order rate and then continued to decrease with another small first-order rate. The change in disintegration time or ejection force versus mixing time was basically the same as that in the hardness. This type of plot was applicable to the mixing magnesium stearate with not only granular but also powdered materials.

Novel oral controlled-release microspheres using polyglycerol esters of fatty acids

Abstract A novel oral controlled-release drug delivery system which consists of microspheres of 75–500 μm in diameter has been designed and developed. A drug is dispersed in a spherical micromatrix of poly-glycerol esters of fatty acids (PGEFs). The microspheres were prepared by a spray-chilling method using a rotating disc and had a narrow particle size distribution. A required size could easily be obtained by altering the spray conditions. In the in vitro dissolution tests, drug release was found to be affected by the size of the microspheres and the drug content in the microspheres. However, release of the drug could be regulated by selecting an appropriate hydrophile-lipophile balance value of PGEF. PGEF-based micromatrix system could provide stable controlled release, i.e., the surface morphology and the release profiles did not change during a long storage period at 40°C while the surface morphology and the release profiles changed after only one-day storage at 40°C when hydrogenated cotton seed oil (HSCS) was used as the matrix base.

Stabilization of a new antiulcer drug (Lansoprazole) in the solid dosage forms

AbstractIn the previous study, we clarified that enteric granules were appropriate dosage forms of lansoprazole. The establishment of these formulations, however, was difficult because some of the excipients needed for these formulations are incompatible with the drug. We examined the effects of adding magnesium carbonate as an alkaline stabilizer and could get stable enteric granules. We also discuss the mechanism of stabilization.

Chromatographic analysis of sucrose esters of long chain fatty acids

The procedure of the quantitative analysis of the components of sucrose ester products is described. By thin-layer chromatography, sucrose ester products have been separated into their components: mono-,di-,tri-, and higher esters. The individual components have been extracted from the plate and determined colorimetrically by using anthrone reagent. Standard substances of monoesters, diesters and triesters, which have been synthesized from gas-chromatographically pure methyl esters of fatty acids, have been isolated by column chromatography and identified by elemental analysis, colorimetric determination and N.M.R. determination.

Manufacturing Method of Stable Enteric Granules of a New Antiulcer Drug (Lansoprazole)

AbstractIn our previous studies, we clarified that enteric granules are an appropriate dosage form for lansoprazole, and we demonstrated that enteric granules could be produced when magnesium carbonate was added as an alkaline stabilizer.These granules however were found to be some unstable under severe conditions because some of the excipients are incompatible with lansoprazole. We therefore attempted granulation not using these incompatible excipients and could obtain more stable enteric granules using a centrifugal fluid-bed granulator instead of an extruder-spheronizer. We also compared the absorption and dissolution properties of the enteric granules manufactured by these two methods.

Frictional Properties of Tablet Lubricants

AbstractSome frictional properties of tablet lubricants were determined. The friction coefficients and the adhesion forces of six lubricants were evaluated by the method proposed previously. The ejection force against the radial force for each lubricant yielded a straight line through the origin, so that the adhesion forces of these lubricants were estimated to be almost zero. All lubricants had low friction coefficients when they alone were compressed. The value for metal stearate was the smallest and that for talc was the largest. The affinity of the lubricants to the die wall, another important property of the lubricants, was also determined. After the die wall was conditioned by the tabletings of each lubricant alone, the serial tabletings of lactose granulates in the die were carried out. The increasing rate of ejection force in the conditioned die in a serial tableting was different for every pretreatment of each lubricant. The affinity of magnesium stearate to the die wall surface was superior to t...

Anti-hypertensive effect of oral controlled-release microspheres containing an ACE inhibitor (Delapril hydrochloride) in rats

Abstract— An oral controlled‐release drug delivery system based on microspheres of polyglycerol esters of fatty acids (PGEFs), was applied to an anti‐hypertensive, delapril hydrochloride. The in‐vitro release profile was controlled by selecting a PGEF with an appropriate hydrophilic‐lipophilic balance value for the matrix. The microspheres from which 80% of the drug was released in 6 h were orally administered to rats. The plasma concentration of the active metabolite was sustained after administration of the microspheres in comparison with administration of a solution. The in‐vivo release profile was in good agreement with the in‐vitro release profile. When the microspheres were administered, the pharmacological effect of delapril hydrochloride on the angiotensin I‐induced pressor response was also sustained showing consistency with the plasma concentration‐time curve.

Evaluation of changes in drug particle size during tableting by measurement of dissolution of disintegrated tablets

Three poorly soluble drugs (chloramphenicol, phenacetin and prednisolone) were compressed into tablets of 10% drug content on a physical testing instrument at three different compression pressures. The dissolution profiles were determined by a modification of the U.S.P. method for drug suspensions, granules before compression, disintegrated and intact tablets. By comparison of the dissolution rates for disintegrated tablets with those for granules before compression, or suspensions, it is possible to separate the change in particle size during compression from the pressure‐dependent dissolution behaviour of intact tablets. A comparative measurement of dissolution for disintegrated tablets with that for granules provides a useful method for elucidating the particle bonding or cleavage within the tablet during compression.

Effect of drug content and drug particle size on the change in particle size during tablet compression

Three size fractions for each of three poorly soluble drugs were compressed into 10 mm diameter tablets of four different dilution ratios. The compression was carried out on a physical testing instrument at four compression levels of 49·0, 98·1, 196·2 and 294·3 MN m−2. The effect of drug content and drug particle size on the change in particle size during tableting was examined by the determination of the dissolution rate for disintegrated tablets. A linear relation was obtained when plotting ***1n(T80%) versus drug content. There was a critical particle size where the phenomena of cleavage and bonding during tableting balanced each other, but this varied with drug content.

Mprovement in Pressure-Dependent Dissolution of Trepibutone Tablets by Using Intragranular Disintegrants

AbstractIn developing compressed tablets trepibutone 40mg, dissolution studies indicated that the compression pressure applied exerted strong influence on drug dissolution from the tablets. It was found that the incorporation of disintegrants in the granular formulation prevented the decrease in dissolution rate of drug from tablets by compression. Instead of the intragranular disintegrants, incorporation of a rubber powder, which does not swell at all in water and has some elastic recoveries after compression, did not improve the drug dissolution from tablets. It was concluded that the addition of disintegrants in the granular formulation resulted in little prevention of the particle aggregation during compression. The swelling of disintegrant grains in water is considered to play an important part in the deaggregation of drug particles