F.C. Lam

Albumin microspheres. III. Synthesis and characterization of microspheres containing adriamycin and magnetite

Abstract Adriamycin-associated bovine serum albumin microspheres (Adr-BSA), plain magnetic BSA microspheres (Fe-BSA) and adriamycin-associated magnetic BSA microspheres (Adr-Fe-BSA) were prepared by heat stabilization at different temperatures and evaluated for their size, hydration characteristics, drug and/or magnetite entrapment, Fe 3 O 4 distribution within particles and drug release properties. It was demonstrated that microspheres with a mean diameter of less than 1 μm can be prepared at temperatures between 105 and 150° C, in the presence of adriamycin and/or magnetite. Equilibrium hydration with these particles was attained in about 2 h after soaking in normal saline at 37° C. The degree to which the particles increase in size was dependent on their stabilization temperature. The entrapment of adriamycin was influenced by the presence of magnetite as well as the temperature employed during the carrier stabilization. Maximum entrapment of adriamycin in Adr-Fe-BSA microspheres, after 4 washings, was obtained at 120° C. The presence of adriamycin significantly affected the entrapment and distribution of Fe 3 O 4 in albumin microspheres. The release rate of adriamycin entrapped within Adr-BSA and Adr-Fe-BSA microspheres was dependent on the presence of magnetite as well as the stabilization temperature of the carrier.

Factorial design based optimization of the formulation of albumin microspheres containing adriamycin.

The use of factorial design in the formulation of adriamycin-associated albumin microspheres, using the heat-stabilization technique, is illustrated. The effect of stabilization temperature, protein concentration and stabilization time on the entrapment and recovery of adriamycin in microspheres have been investigated using a 2 x 4 x 4 factorial design. The associated drug content in unwashed and four times washed microspheres was determined using HPLC. Maximum drug association and drug recovery were obtained from microspheres synthesised using 25 per cent w/v albumin solution and stabilized at 120 degrees C for 2.5 min. Under these conditions, the entrapped and total associated drug content of the microspheres was about 4 per cent and 12 per cent w/w respectively, and the drug recovery was about 75 per cent. The in vitro dissolution study carried out using dynamic dialysis revealed that the release of adriamycin from these particles follows a bi-phasic pattern. The results demonstrate that use of short stabilization time, low protein concentration and low stabilization temperature are required for the formulation of microspheres with high adriamycin content.

Investigation of the Stability of Doxorubicin Hydrochloride Using Factorial Design

AbstractUsing drug concentration remaining at a given time as the criterion, a 24x3 factorial design has been employed to investigate the effects of temperature, light, media (aqueous or organic/aqueous), ionic strength and pH on the stability of doxorubicin hydrochloride. Following the application of first order kinetics, and assuming an additive model, the statistical significance of the factors and their interactions have been determined using analysis of variance (ANOVA) on the dependent variable ln(lnCo-InC). The results indicate that temperature, pH and media are the major factors responsible for the stability of drug. The two-way interaction between temperature and pH, and the three-way interaction between temperature, light and ionic strength are also significant. It is found that doxorubicin is more stable in non-aqueous media at low temperature and low pH values. A combination of darkness and low ionic strength is also conducive to its stability.

A stability study of aqueous solution of norfloxacin

AbstractA reversed-phase ion-pair high performance liquid chromatographic assay, which can simultaneously determine norfloxacin and its decomposition products, formyl piperazine and ethylenediamine analogs in aqueous media, has been developed. This assay has been applied to a stability study of norfloxacin in aqueous media. The effects of temperature, pH, oxygen and light on norfloxacin have been investigated using a 23×3 factorial design. Results indicate that oxygen, light, temperature and pH have significant effect on the stability of norfloxacin solution. Norfloxacin is most stable at acidic and basic pH, in darkness, in the absence of oxygen and at low temperature.

A stability study of amphotericin B in aqueous media using factorial design

Abstract A reversed phase ion-pair high-performance liquid chromatography assay has been developed for the determination of amphotericin B (AmB) in aqueous media. This assay has been applied to a factorial stability study of AmB. The effects of temperature, pH, ionic strength, surfactant concentration, oxygen and light on AmB have been investigated using a 2 5 × 3 factorial design. Results indicate that oxygen, light and temperature have significant effects on the stability of AmB solutions. Interactions between temperature and ionic strength, ionic strength and surfactant, pH and temperature and surfactant have also been identified. It is concluded that AmB is most stable in the absence of light, in oxygen-free environment and at low temperatures.

Formulation Optimization of a Hydrocolloid Dressing

AbstractA methodology of mixture experiments has been applied to the formulation of a multicomponent hydrocolloid dressing. Using an extreme vertices statistical design, a semi-occlusive dressing composed of dextran, phospholipid, glycerol and sodium lauryl sulphate has been formulated, which checks evaporative water loss (EWL) from the excised wound surface of rats to an optimum level.

Albumin microspheres. IV. Effect of protein concentration and stabilization time on the release rate of adriamycin

Abstract The effects of protein concentration and heat-stabilization time at 120 ° C on the release rate of adriamycin from microspheres have been investigated. The albumin concentration and the stabilization time of the microspheres were varied from 20 to 40% w/v and from 2.5 to 10 min, respectively. The release studies carried out using dynamic dialysis demonstrated that irrespective of the protein concentration and stabilization time, the initial release rate was significantly higher than the terminal release rate of adriamycin from these particles. Whereas variation in the albumin concentration was shown to cause comparable changes in the initial and the terminal release rate constants of adriamycin, the variation in the stabilization time predominantly affected the terminal release rate constants. The results indicate that protein concentration as well as the heat-stabilization time of albumin microspheres may be used to control the release of entrapped drug.