[Sustained-release progesterone vaginal suppositories 3-development and clinical feasibility testing].

  Although progesterone vaginal suppositories (hospital-formulated) are used for the treatment of infertility, their half-life is so short that multiple doses are required. In this study, we aimed to develop sustained-release vaginal suppositories suitable for clinical use which maintain an effective blood concentration by once-a-day treatment, and prepared 7 types of suppository containing the sustained-release progesterone tablets to characterize their sustained-release performance. We selected one candidate suppository among them, taking recovery rate, reproducibility, and hardness, as well as the sustained-release performance into consideration.

Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration.

[Revealing the essence of powders: from the base to the application].

My main research fields are powder technology, especially solid dosage form, from basic ones to applied ones. Basic ones are physical properties of powder and its packing, compression and computer simulation. Applied ones are preparation and evaluation of granulation, tableting, improvement of solubility of water poor-soluble drug, controlled release tablet and fast disintegrating tablet in the oral cavity.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules V. Release properties of ethylcellulose layered matrix granules.

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. In previous papers, a combination of the square-root time law and cube-root law equations was confirmed to be a useful equation for qualitative treatment. It was also confirmed that the combination equation could analyze the release properties of layered granules as well as matrix granules.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules IV.(1)) Evaluation of the controlled release properties for in vivo and in vitro release systems.

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. The dissolution test is a very important and useful method for understanding and predicting drug-release properties. It was readily confirmed in the previous paper that the release process could be assessed quantitatively by a combination of the square-root time law and cube-root law equations for ethylcellulose (EC) matrix granules of phenylpropanolamine hydrochloride (PPA).

Preparation of rapidly disintegrating tablets containing itraconazole solid dispersions.

The disintegratability of tablets prepared from two types of solid dispersions containing the water-soluble polymer TC-5 and the enteric polymer HP-55 as an excipient were compared. The disintegratability was better in the tablets of solid dispersions containing non-water-soluble HP-55 than those containing TC-5. In consideration of the dissolubility of solid dispersions containing HP-55, the mean diameter of the solid dispersion (coating powder) must be controlled to 120 microm or less, but as this markedly increases the adhesion/aggregation tendency of the particles (angle of repose: 47 degrees ), control of the adhesion/aggregation tendency emerged as another problem.

Preparation and evaluation of Ibuprofen solid dispersion systems with kollidon particles using a pulse combustion dryer system.

Solid dispersions (SDs) of ibuprofen (IBU) were prepared with four carriers: Kollidon 25, Kollidon 30, Kollidon VA64, and Kollidon CL, using a newly developed pulse combustion dryer system, HYPULCON. Physicochemical properties of the SDs obtained were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM), and Fourier transformation IR spectroscopy (FT-IR). Powder X-ray diffraction (PXRD) showed that the crystal diffraction peaks of IBU in SDs disappeared completely, and in differential scanning calorimetry (DSC) curves, the endothermic peaks of IBU in SDs were not observed.

Improvement of the dissolution rate of nitrendipine using a new pulse combustion drying method.

Solid dispersions (SDs) of nitrendipine (NTD), a poorly water-soluble drug, were prepared with the Hypulcon pulse combustion dryer system, and the physicochemical properties of particles were investigated and compared with those of particles prepared with a spray dryer. The SD particles prepared with Hypulcon using Aerosil and Tween 80 as carriers showed improved properties over those prepared with a conventional spray dryer, such as smaller particle size, tighter particle size distribution, and no agglomeration. Powder X-ray diffraction and differential scanning calorimetry evaluation showed that the drug in the NTD-Aerosil SD prepared with 5% (v/v) Tween 80 solution was dispersed in an amorphous state.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules III. Effects of the dissolution condition on the release process.

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the entire release properties. As the first step, the dissolution test under various conditions is selected for the in vitro test, and usually the results are analyzed following Drug Approval and Licensing Procedures. In this test, 3 time points for each release ratio, such as 0.

Evaluation of bitterness suppression of macrolide dry syrups by jellies.

The purpose of this study was to evaluate the bitterness-suppressing effect of three jellies, all commercially available on the Japanese market as swallowing aids, on two dry syrups containing the macrolides clarithromycin (CAM) or azithromycin (AZM). The bitterness intensities of mixtures of the dry syrups and acidic jellies were significantly greater than those of water suspensions of the dry syrups in human gustatory sensation tests. On the other hand, the mixture with a chocolate jelly, which has a neutral pH, was less bitter than water suspensions of the dry syrups.

Preparation and evaluation of solid dispersions of nitrendipine prepared with fine silica particles using the melt-mixing method.

Solid dispersions (SD) of nitrendipine (NTD), a poorly water-soluble drug, were prepared using the melt-mixing method with hydrophilic silica particles (Aerosil and Sylysia) with different particle size and specific surface areas as carriers. Powder X-ray diffraction and differential scanning calorimetry evaluation showed that NTD in the SDs treated with the melt-mixing method was dispersed in the amorphous state. FT-IR spectroscopy obtained with the SDs indicated the presence of hydrogen bonding between the secondary amine groups of NTD and silanol groups of silica particles.

Preparation and evaluation of solid dispersion for nitrendipine-carbopol and nitrendipine-HPMCP systems using a twin screw extruder.

In the present study, we prepared solid dispersions of the poorly water-soluble drug nitrendipine (NIT) using the twin screw extruder method with high-molecular-weight substances, hydroxypropylmethylcellulosephthalate (HPMCP) and Carbopol (CAR), as carriers. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) evaluation showed that solid dispersions can be formed when NIT-HPMCP and NIT-CAR mixtures are treated with the twin screw extruder method. Fourier Transformation IR Spectroscopy (FT-IR) obtained with NIT-HPMCP and NIT-CAR solid dispersions indicated the presence of hydrogen bonding between the drug and the carriers.

Release from or through a wax matrix system. VI. Analysis and prediction of the entire release process of the wax matrix tablet.

Analysis of the entire release process of the wax matrix tablet was examined. Wax matrix tablet was prepared from a physical mixture of drug and wax powder to obtain basic or clear release properties. The release process began to deviate from Higuchi equation when the released amount reached at around the half of the initial drug amount.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules II. effects of the binder solution on the release process.

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC) matrix granules prepared by an extrusion granulation method were examined. The release process could be divided into two parts; the first and second stages were analyzed by applying square-root time law and cube-root law equations, respectively. The validity of the treatments was confirmed by the fitness of a simulation curve with the measured curve.

Preparation and evaluation of high drug content particles.

To determine how to prepare high drug content particles using a Wurster fluidized bed to determine realizing the miniaturization of solid dosage forms, aspirin was selected as the model drug and granulated without any additive. In this study, the emphasis was on evaluating the key operation factors of airflow rate and atomizing flow volume. The properties of the resulting particles, such as the average diameter, particle strength, appearance, and compressibility using different airflow rates and atomizing flow volumes, were investigated.

Release from or through a wax matrix system. V. Applicability of the square-root time law equation for release from a wax matrix tablet.

To obtain basic and clear release properties, wax matrix tablets were prepared from a physical mixture of drug and wax powder at a fixed mixing ratio. Properties of release from the single flat-faced surface, curved side surface, and/or whole surface of the wax matrix tablet were examined. Then tortuosity and the applicability of Higuchi's square-root time law equation were examined.

Preparation and evaluation of combination tablet containing incompatible active ingredients.

Combination preparation plays an important role in clinical treatment because of its better and wider curative synergism and weaker side effects. However, the existence of incompatibility between active ingredients or between active ingredients and excipients presents a serious obstacle in the preparation of such combination solid dosage forms. In this study, aspirin and ranitidine hydrochloride, between which there existed a chemical interaction, were selected as model drugs.

Measurement and evaluation of the adhesive force between particles by the direct separation method.

We developed a new apparatus to measure the adhesive force between particles with a high resolution of approximately 2 nN. The force was measured directly by applying a pulling force to the particles with a contact needle. In addition, the separation process was observed with a 3CCD camera during the measurement.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules.

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC, ethylcellulose 10 cps (EC#10) and/or 100 cps (EC#100)) matrix granules prepared by the extrusion granulation method were examined. The release process could be divided into two parts, and was well analyzed by applying square-root time law and cube root law equations, respectively. The validity of the treatments was confirmed by the fitness of the simulation curve with the measured curve.

Release from or through a wax matrix system. IV. Generalized expression of the release process for a reservoir device tablet.

Generalization of the release process through the wax matrix layer was examined by use of a reservoir device tablet. The wax matrix layer of the reservoir device tablet was prepared from a physical mixture of lactose and hydrogenated castor oil to simplify the release properties. Release through the wax matrix layer showed zero-order kinetics in a steady state after a given lag time, and could be divided into two stages.

Release from or through a wax matrix system. III. Basic properties of release through the wax matrix layer.

Release property of reservoir device matrix tablet was examined. Wax matrix layer was prepared from physical mixture of lactose and hydrogenated castor oil to obtain basic release properties. Release process showed zero order kinetics in a steady state after a given lag times, and could be divided into two stages.

Preparation of solid dispersion for ethenzamide-carbopol and theophylline-carbopol systems using a twin screw extruder.

In the present study, we prepared solid dispersions of water-insoluble and soluble drugs (ethenzamide (ETZ) and theophylline (THEO)) by the twin screw extruder method, which made it possible to control both kneading and heating at the same time under the fusion point of each drug, using three types of the controlled-release high-molecular-weight substance Carbopol (CAR) as the carrier. The solid dispersions obtained were evaluated and compared with those prepared by the organic solvent method. These products showed significantly increased solubility of ETZ, but the solubility of THEO was reduced indicating that CAR slows the release of THEO.

Release from or through a wax matrix system. II. Basic properties of release from or through the wax matrix layer.

In order to examine basic properties of release from and through wax matrix layer, reservoir device matrix tablet was prepared from a physical mixture of hydrogenated caster oil and drug that was the same one in the reservoir. Release process could be divided into two stages. The first stage was the formation process of water channel by dissolving the drug in the wax matrix layer, and dissolved drug was released from the matrix layer following the square-root-of-time law equation.