Improved dissolution of an insoluble drug using a 4-fluid nozzle spray-drying technique

Chem Pharm Bull (Tokyo). 2004 Sep;52(9):1066-70. doi: 10.1248/cpb.52.1066.

Abstract

A solid dispersion of the drug can be made using a polymer carrier to improve solubility. Generally, drugs become amorphized when solid dispersion is formed using a polymer carrier. In such high energy conditions, the solubility of the drug molecule is increased. We previously prepared solid dispersion using a spray-drying technique and reported its solubility and crystallinity. In this study, hydroxypropylmethylcellulose (HPMC) was used as the carrier, and tolubutamide was the model drug, which is water-insoluble. Solubility was evaluated by preparing a solid dispersion using a newly developed 4-fluid nozzle spray dryer. Observation of particle morphology by scanning electron microscopy (SEM) revealed that the particles from the spray drying were atomized to several microns, and they had also become spherical. Assessment of the crystallinity of the spray-dried particles by powder X-ray diffraction and differential scanning calorimetry demonstrated that the tolbutamide had been amorphized, forming a solid dispersion. The apparent release rate constant K of the drug from the spray-dried particles was 4 to 6 times faster than the original drug in pH 1.2, and it was also 1.5 to 1.9 times faster than the original drug in pH 6.8. The 70% release time (T(70)) of the drug from the spray-dried particles was 20 to 30 times faster than the original drug in pH 1.2 solution as well as 2 to 3 times faster than the original drug in pH 6.8 solution. Pharmaceutical preparations prepared in this way using the 4-fluid nozzle system spray dryer formed composite particles, resulting in a remarkably improved dissolution rates of the drug.

MeSH terms

  • Crystallization
  • Dosage Forms
  • Drug Carriers / chemistry
  • Hypoglycemic Agents / chemistry
  • Hypromellose Derivatives
  • Kinetics
  • Methylcellulose / analogs & derivatives*
  • Methylcellulose / chemistry*
  • Microscopy, Electron, Scanning
  • Models, Chemical
  • Particle Size
  • Solubility
  • Technology, Pharmaceutical / instrumentation
  • Tolbutamide / chemistry*

Substances

  • Dosage Forms
  • Drug Carriers
  • Hypoglycemic Agents
  • Hypromellose Derivatives
  • Methylcellulose
  • Tolbutamide