Toguchi Hajime

Factors influencing the profiles of TRH release from copoly(d,l-lactic/glycolic acid) microspheres

Abstract Copoly(d,l-lactic/glycolic acid) (PLGA) microspheres containing thyrotropin releasing hormone (TRH) were prepared using an in-water drying method through a (w/o)/w emulsion. Various factors which affect TRH release from microspheres were examined both in vitro and in vivo. The drug release was affected by the drug loading level, the molecular weight of PLGA, and the lactic acid/glycolic acid (LA/GA) ratio of PLGA. The effect of the drug loading level on the initial burst differed widely with changes in the molecular weight of PLGA. The initial burst increased with decreasing molecular weight of PLGA. After the initial burst, the release rate was dominated mainly by the degradation of PLGA; the lower the molecular weight of PLGA, the faster the release rate. The release rate was also affected by the LA/GA ratio of the PLGA. The microspheres prepared with a higher GA content of PLGA exhibited a faster release rate. In the in vivo study in rats, the microspheres also released the peptide sustainedly over a long period after s.c. injection.

Effects of counteranion of TRH and loading amount on control of TRH release from copoly(dl-lactic/glycolic acid) microspheres prepared by an in-water drying method☆

Abstract The preparation of injectable sustained release microspheres of TRH was investigated. The drug was encapsulated in copoly(dl-lactic/glycolic acid) (PLGA) using an in-water drying method through a w/o/w emulsion. The predominant factors influencing the entrapment ratio of TRH in the microspheres and the release rate of TRH from the microspheres were the loading amount and the dissociation state of the drug. Microspheres of TRH encapsulated as a free base at an adequate concentration provided a small initial burst followed by a zero-order prolonged release regardless of the high water solubility of the drug. The addition of strong acids to the inner aqueous phase interfered with the encapsulation efficacy and caused a large initial burst. The ionic interaction between the basic functional group of TRH and the carboxylic acid end group of PLGA during the preparation is necessary to produce a rigid matrix of the microspheres. This method is applicable to the microencapsulation of other water-soluble basic peptides in PLGA.

Preparation and characterization of copoly(dl-lactic/glycolic acid) microparticles for sustained release of thyrotropin releasing hormone by double nozzle spray drying method

Abstract Copoly(dl-lactic/glycolic acid) microparticles for sustained release of a water soluble drug (Thyrotropin releasing hormone: TRH) were prepared by a spray drying method. In the case of double nozzle spray drying (DNSD) using acetonitrile, the effect of TRH loading amount on the initial burst was smaller than that with in-water drying. The microparticles prepared by DNSD and loaded with up to 10% TRH exhibited a small initial burst followed by a constant release rate over 4 weeks. The drug release from the polymer was much faster than the polymer weight loss. The mean particle size of the spray dried microparticles was smaller than that with in-water drying. Acetonitrile used in DNSD is a less toxic organic solvent than dichloromethane, and the residual amount in the microparticles was similar to that in the in-water drying method. In conclusion, the production of biodegradable microparticles by the double nozzle spray drying method should be an attractive alternative to conventional microencapsulation methods.

Mechanism of drug release from polyglycerol ester of fatty acid-based microspheres

Abstract The factors influencing the drug release and the mechanism of the drug release from the spherical, polyglycerol ester of fatty acid (PGEF)-based microspheres has been elucidated. The release rates of theophylline, phenylpropanolamine hydrochloride (PPA) and prednisolone were examined. The drug release could be regulated by choosing an appropriate hydrophile-lipophile balance value of PGEF. The drug solubility in water affected the release rate of the drug. The particle size of the microspheres did not change during drug release. In addition, the paddle speed did not affect the release rate. Since the release rate could be expressed by Janders equation which considers the change in the interfacial area where the actual release of a solid drug occurs, the release from the microspheres is found to be a diffusion controlled process within the micromatrix.