Hiroshi Ozawa

Improvement of photostability of ubidecarenone in the formulation of a novel powdered dosage form termed redispersible dry emulsion

Abstract Ubidecarenone, which has low photostability and is poorly absorbed in the intestine, was formulated into a novel powdered dosage form designated as a redispersible dry emulsion. In preparing the system, an oily solution containing the drug and a colorant emulsified in an aqueous solution of a surfactant (Pluronic F-68) were spray-dried with a suitable excipient. The resultant dry emulsion particles have good flow properties and readily release the oily droplets to form stable emulsions on rehydration. The redispersibility, i.e., the conversion to the original emulsion from the dry emulsion form, was found to be closely related to the viscosity of the oily carrier. The photostability of the drug dissolved in the oily carriers was much improved in the presence of colorants. The kinetics data for photolytic degradation of the drug in the dry emulsion particle were analyzed to clarify the effect of the amount of excipient and colorant on the photostability of the drug in the particle.

Evaluation of the correlation between in vivo and in vitro release of phenylpropanolamine HCl from controlled-release tablets

Abstract The dissolution behavior of two controlled-release matrix tablets, formualtions A and B, containing phenylpropanolamine HCl as a model drug was studied using a paddle method and a paddle-beads procedure. The paddle-beads method involves a system in which polystyrene beads are inserted into the dissolution medium to cause mechanical destruction or frictional force. These tablets have the advantages of pH- and agitation-independent release performance in vitro using the paddle method. These matrices and solution were orally administered to six beagle dogs, and the results were analyzed by deconvolution. In vitro dissolution curves using the paddle method did not coincide with the in vivo profiles in the fasted condition, while in vitro release using the paddle-beads method was similar to the in vivo profile in the fasted condition in dogs. The paddle-beads method may be useful for investigating in vivo/in vitro correlation of controlled-release dosage forms.

Determination of the mechanical impact force in the in vitro dissolution test and evaluation of the correlation between in vivo and in vitro release

Abstract The mechanical impact force in the paddle-beads method was determined. A manometric catheter was passed into the dissolution vessel through a hole, and the mechanical impact force was measured. In the present study, this mechanical force was evaluated as an impulse. The impulse increased with increasing number of beads added in the medium; in particular, the impulse increased markedly with more than 2500 beads in 250 ml dissolution medium. A close relationship was observed between the drug release rate and impulse. The profile of in vitro release using the paddle-beads method with rotation at 25 rpm in 250 ml of medium containing 2500 beads was similar to that of in vivo release in the fasted condition in dogs.

Design of Redispersible Dry Emulsion as an Advanced Dosage Form of Oily Drug (Vitamin E Nicotinate) by Spray-Drying Technique

AbstractAn oily drug, dl-α-tocopherol nicotinate (VEN) was transformed to the newly developed powdered form, termed dry emulsion, by spray-drying the emulsified VEN or oily solutions of VEN with additives. The drug releasing property from the resultant particles was dependent on various factors such as the emulsifying method and the type and amount of the oily carrier and surfactant formulated. The desired releasing property was offered by use of medium chain triglyceride (MCT) as the oily carrier and polyoxyethylene-polyoxypropylene-blockcopolymer (Pluronic F-68) or polyoxyethylenesorbitan monolaulate (Tween 80) as the emulsifying agent. The difference in drug releasing property with various formulations was found to be mainly attributed to the difference in physical state of VEN surfactant in the dry emulsion particle, which was detected by differential scanning calorimetry.

Effect of moisture on crystallization of theophylline in tablets

AbstractNeedle-like crystals appeared on the surface of theophylline tablets containing anhydrous theophylline, hygroscopic materials such as potassium, and other formulation ingredients, when stored under conditions of high relative humidity. X-ray powder diffraction studies on these crystals showed that anhydrous theophylline was converted to the hydrate.Crystal growth was accelerated by increased moisture uptake in tablets containing the hygroscopic materials polyethylene glycol 6000 or sodium chloride. The appearance of needle-like crystals on the surface of tablets resulted in a decrease in the rate of release of theophylline.

Water behavior during drug release from a matrix as observed using differential scanning calorimetry

Abstract A solid made from a dissolved mixture of hydroxypropylcellulose and ethylcellulose (SMH) was used as a controlled-release filler, and phenylpropanolamine hydrochloride (PPA) was used as a model drug. With increases in weight fraction of hydroxypropylcellulose (WFH) in the matrix, drug release and water penetration into the matrix decreased Water behavior daring drug release from a SMH matrix was studied by using differential scanning calorimetry (DSC). During the initial stage of dissolution, the water penetrating into the matrix acted as non-freezing water. As the water content of the matrix increased and freezable water was detected at levels that were related to drug release. It was also presumed that before hydrating the whole matrix, water penetrated into the dry portion of the matrix and hydrated the polymer, while further penetrating water did not increase the water content of the hydrated portion, but newly hydrated a dry portion of the matrix.

Improvement of the stability of water-in-oil-in-water multiple emulsions by the addition of surfactants in the internal aqueous phase of the emulsions

Abstract In order to improve the stability of w/o/w emulsions, an attempt was made to elucidate the influence of addition of hydrophilic surfactants into the internal aqueous compartment of the emulsion, on the breakdown of the suspending vesicular globules of w/o/w emulsion, the changes in diameter of the internal aqueous compartments and of the suspending vesicular globules of w/o/w emulsion, as compared with emulsions without additives and with addition of sodium chloride. It was also attempted to measure the effect of addition of hydrophilic surfactant to the three different phases on the stability of w/o/w emulsions. The stability of diluted w/o/w emulsions with a large difference in osmolarity between the internal aqueous compartments and the external aqueous phase was also tested, w/o/w emulsions were prepared by the two-step emulsification procedure. New coccine was employed as a marker to check the yield of formation and the breakdown of the w/o/w emulsions. Sodium octanesulfonate was used as an additive in the internal aqueous compartment of the w/o/w emulsions as well as sodium chloride. Polyoxyethylene (20) sorbitan monooleate was used as an additive to the three different phases of the emulsions. The stability of w/o/w emulsions, as determined by coalescence of internal aqueous compartments and their increase in size by the influx of water to the internal aqueous compartment from the external aqueous phase, was improved by the addition of hydrophilic surfactant in the internal aqueous compartments of the emulsions. This was observed even under the condition of a large difference in osmolarity between the internal aqueous compartments and the external aqueous phase, and was affected by the concentration of hydrophilic surfactant. The addition of sodium chloride to the internal aqueous compartments and of hydrophilic surfactant to the external aqueous phase did not improve the stability of w/o/w emulsions. Only the addition of hydrophilic surfactant into the internal aqueous compartments was demonstrated to inhibit both coalescence of internal aqueous compartments and influx of water to the internal aqueous compartment from the external aqueous phase. On the other hand, the addition of hydrophilic surfactant into the oil phase was observed not to inhibit coalescence but water influx.

Preparation of a novel type of controlled-release carrier and evaluation of drug release from the matrix tablet and its physical properties

Abstract Solved mixtures of hydrogels (SMH), composed of hydroxypropylcellulose (HPC), a pseudo-hydrogel, and ethylcellulose, a water-insoluble polymer, were prepared by solvent evaporation. Phenylpropanolamine hydrochloride was used as a model drug. The amount of drug released from a matrix tablet containing SMH powder and the drug increased with decreasing weight fraction of HPC (WFH) in SMH. SMH showed improved properties compared to HPC alone, for example, flowability and hydroscopicity. These properties increased with decreasing WFH. The sorption apparatus described in this study is capable of an immediate, sensitive and accurate response to initial moisture sorption. The kinetics of moisture sorption measurement using this apparatus is useful for a preliminary study.

Improvement of the formation percentage of water-in-oil-in-water multiple emulsion by the addition of surfactants in the internal aqueous phase of the emulsion

Abstract In order to improve the formation percentage of w/o/w emulsions, experiments were conducted in order to elucidate the influence of the addition of various kinds of surfactants in the internal aqueous phase of the emulsion, the formation percentage of w/o/w emulsion as compared with that without additives, and with sodium chloride or sorbitol. Several physico-chemical properties of intact w/o/w emulsion or each phase, such as the osmolarity, interfacial tension and viscosity, were investigated in order to determine the governing factor in improving the formation percentage of w/o/w emulsion. w/o/w emulsion was prepared via a two-step emulsification procedure. New coccine was employed as a marker to evaluate the formation percentage of w/o/w emulsion. Sodium alkylsulfonate, sodium alkylsulfate, sodium alkylcarbonate and polyoxyethylene (20) sorbitan monooleate were used as additives in the internal aqueous phase of w/o/w emulsion as well as sodium chloride and sorbitol. The formation percentage of w/o/w emulsion was improved by increasing the concentration of the additives, viz., various kinds of surfactants in the internal aqueous phase of the emulsion, as well as sodium chloride or sorbitol. This could be attributed to a decrease in interfacial tension between the internal aqueous phase of the w/o/w emulsion and the oily phase of the emulsion.

Application of an ovomucoid-conjugated polymer column for the enantiospecific determination of chlorprenaline concentrations in plasma

An ovomucoid-conjugated polymer column was prepared for the liquid chromatographic resolution of racemic compounds. The column showed strong retention of acidic solutes, a characteristic attributed to the structure of the stationary phase support gel. Although the efficiency of the column was lower than that of an ovomucoid-conjugated silica gel column, enantiospecific chlorprenaline determination in plasma was achieved with solute amounts from 1.0 ng to 0.1 microgram.