ABSTRACT
The effect of storage on the physical stability of solid dispersions of triamterene or temazepam in polyethylene glycols was studied using differential scanning calorimetry (DSC), particle-size analysis and dissolution methods. The enthalpies of fusion of the carriers, without included drug and previously fused and crystallized, increased on storage. Analysis of similarly treated solid dispersions, containing either 10% temazepam or 10% triamterene, showed that each drug influenced the morphology of the polyethylene glycol (PEG). The enthalpies and melting points of the solidus components of the dispersions' carriers were initially reduced after preparation, but on storage these increased. The particle sizes of the drugs dispersed in the PEGs increased on storage. The changes in dissolution after storage of triamterene or temazepam dispersions were smaller for dispersions in PEG 1500 than for dispersions in PEGs of higher molecular weight (PEG 2000, PEG 4000 or PEG 6000) in which the reduction in dissolution was particularly marked during the first month of storage. The rank order of changes in dissolution were PEG 1500 < < PEG 2000 < PEG 4000 approximately PEG 6000.
Subject(s)
Anti-Anxiety Agents/chemistry , Diuretics/chemistry , Drug Storage/standards , Polyethylene Glycols/chemistry , Solvents/chemistry , Temazepam/chemistry , Triamterene/chemistry , Anti-Anxiety Agents/metabolism , Calorimetry, Differential Scanning , Crystallization , Diuretics/metabolism , Drug Carriers/chemistry , Drug Carriers/metabolism , Drug Stability , Molecular Weight , Particle Size , Polyethylene Glycols/metabolism , Solubility , Solvents/metabolism , Temazepam/metabolism , Temperature , Thermodynamics , Triamterene/metabolismABSTRACT
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. Solidification from melts, investigated by differential scanning calorimetry using cooling cycles, showed a tendency of the drugs, carriers or their dispersions to supercool. The degree of supercooling depended on the rate of cooling, the drug content and, for the PEGs, on the molecular weight. PEG 1500 and PEG 2000 gave one morphological form, irrespective of cooling rate; PEG 4000 and PEG 6000 solidified into at least two forms, depending on the cooling rate. Incorporation of drugs affected the morphology of the PEGs during solidification. The rate of crystal growth was, furthermore, influenced by the fusion temperature, molecular weight and the degree of supercooling. The degree of crystallinity, as measured by the enthalpies of solidification, decreased with increasing cooling rate. The results show that reducing the rate of solidification could lead to incomplete solidification, giving products that are liable to change on storage.
Subject(s)
Pharmaceutic Aids/chemistry , Polyethylene Glycols/chemistry , Temazepam/chemistry , Triamterene/chemistry , Calorimetry, Differential Scanning , Capsules , Crystallization , TemperatureABSTRACT
Poly(epsilon-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.
