Stephen K. Dordunoo

Solubility and stability of taxol: effects of buffers and cyclodextrins

Abstract The degradation kinetics of taxol in aqueous solutions were investigated at 37°C over a pH range of 1–9. The hydrolysis rates followed pseudo first-order kinetics with respect to residual taxol concentration. The pH-rate profile at 37°C showed that a maximum stability of taxol occurred in the pH 3–5 region. The effect of γ-cyclodextrin (γCD), hydroxypropyl-γ-cyclodextrin (HPγCD) and hydroxypropyl-β-cyclodextrin (HPβCD) on the solubility and stability of taxol was also investigated. Taxol was more stable in cyclodextrin solution than in buffer solution of comparable pH. The solubility of taxol in water increased in the presence of cyclodextrins with HPβCD giving the greatest increase in taxol solubility. Taxol (as received) was anhydrous and on suspension in water, it dissolved to form a supersaturated solution which recrystallized as a hydrate of lower solubility. Taxol formed predominantly second order complexes with the cyclodextrins. Complexes of taxol with HPβCD were more stable than those of HPγCD or γCD. Further increase in the solubility of taxol was observed when ethanol was added as a co-solvent.

Taxol encapsulation in poly(ɛ-caprolactone) microspheres

Poly(ɛ-caprolactone) (PCL) microspheres containing taxol were prepared by the solvent evaporation method and tested for angiogenesis inhibition using the chick chorioallantoic membrane (CAM) model. Very high encapsulation efficiencies (95%) for taxol in PCL microspheres were obtained. In vitro release studies showed about 25% of the loaded drug was released in 6 weeks from microspheres containing 5% taxol. Studies with the CAM showed that taxol released from the microspheres induced vascular regression and inhibited angiogenesis.

Release of taxol from poly(ϵ-caprolactone) pastes: effect of water-soluble additives

Abstract We have developed a taxol-loaded polymeric surgical paste for application at tumor resection sites. The paste vehicle is based on poly( ϵ -caprolactone) (PCL), a low melting, biodegradable, biocompatible polymer containing dispersed water-soluble additives. Following gentle heating to between 44–56°C, the paste can be applied in the molten state from a syringe to tumor resection sites. Taxol/additives were co-precipitated, pulverized and incorporated into molten low molecular weight PCL. The taxol/additive/PCL composite was characterized using swelling in water, drug release into phosphate buffered saline (pH 7.4) at 37°C and scanning electron microscopic studies on samples suspended in water. In vivo drug release and anti-angiogenic activity of the composites were evaluated using the chick chorioallantoic membrane (CAM) assay. In addition, in vivo efficacy was investigated using a subcutaneous tumor in mice. The in vitro release of taxol from PCL was increased by the addition of water-soluble agents. Taxol released from the matrix inhibited angiogenesis in the CAM model and caused a mean tumor regression of about 63% in a mice tumor model.

Solidification Studies of Polyethylene Glycols, Gelucire 44/14 or their Dispersions with Triamterene or Temazepam

The solidification of polyethylene glycols (PEG 1500, PEG 2000, PEG 4000, PEG 6000), gelucire 44/14 or their dispersions containing triamterene or temazepam were studied to assess the feasibility of using these dispersions to liquid‐fill hard gelatin capsules.