Phosphate buffer formulations

FIGURE 1 Rate of polyanhydride degradation versus time. PCPP and SA copolymers were formulated into 1.4-cm-diameter disks 1 mm thick by compression molding, and placed into a 0.1 M pH 7.4 phosphate buffer solution at 37°C. The cumulative percentage of the polymer which degraded was measured by absorbance at 250 nm. 

Fig. 17.13. Electropherograms obtained for the analysis of a nasal formulation for the determinations of benzalkonium chloride (BC) in the presence of active pharmaceutical ingredient (R91274) and other placebo ingredients. Conditions 75 mM sodium phosphate buffer, pH = 2.3, 35 cm fused silica capillary (effective length 28.5 cm) x 75 pm I.D., injection 10 s at 35mbar, 20°C, 15 kV (positive polarity) resulting in a current of approximately 95 pA, detection UV 215 nm.

Once the protein is purified, it will be formulated to produce the drug product. This could be as simple as diluting the protein in phosphate-buffered saline, or as complex as addition of excipients and lyophilization. The mark of... 

Figure 2 In vitro cytotoxic activity on B16F1 melanoma cells of the duplex drugs in liposome formulations and of ETC dissolved in phosphate buffered saline. The corresponding IC50 values in mM are shown on the bars. Abbreviations ara-C-NOAC, arabinocytidylyl-N" -octadecyl-l-P-D-arabinofuranosylcytosine 5-FdU-NOAC, 2 -deoxy-5-fluorouridylyl-N" -octadecyl-l -P-D-arabinofuranosylcytosine ETC, ethynylcy-tidine [l-(3-C-ethynyl-P-D-ribopentafuranosyl)-cytosine] NOAC, ISf-octadecyl-ara-C PBS, phosphate buffered saline.

AmB formulations were dispersed in phosphate-buffered saline (PBS) at different concentrations (0.1 lOOpg/mL) and incubated for five minutes at 37°C. Freshly isolated human erythrocytes were then added to a final hematocrit of 2% and incubated at the same temperature for 30 minutes. After centrifugation, the supernatant was removed and the RBC pellet was lysed with sterile water. The hemoglobin remaining in the pellet was estimated from its absorption at 560 nm recorded with a spectrophotometer. The percentage hemolysis was calculated from the difference between the hemoglobin remaining in the test samples and the control incubated with PBS alone. 

The pH dependence of dorzolamide solubility was also determined between pH 4.0 and 7.0, using acetate, citrate, and phosphate buffer solutions to set the desired pH. These data are collected in Table 2 (also plotted in Figure 4), and show a maximum solubility of approximately 40 mg/mL at pH 5.6. The equilibrium solubility decreases to approximately 13 mg/mL at pH 6 and 4 mg/mL at pH 7.0. These data indicate that in order to have a stable 2% solution for an ophthalmic formulation, the solution pH should be maintained below 5.8. At pH values exceeding 5.8, precipitation of the free base could occur. 

Novolin is available in four formulations Regular (R), NPH (N), Lente (L), and Novolin 70/30. They correspond to the several formulations of Humulin. Novolin 70/30, Novolin N, and Novolin R are supplied in prefilled cartridges and in prefilled disposable syringes. Velosulin BR is a sterile solution of human insulin (rDNA origin) in a phosphate buffer. 

A schematic of the INSIGHT screening tool is shown in Figure 4A. The INSIGHT screen consists of two polycarbonate or Teflon plates, each 12.7 mm thick (84). The top plate consists of a square matrix of 100 wells (each 3 mm in diameter). The bottom plate contains a symmetric matrix of 100 wells. The wells in the top plate act as the donors, and the wells in the bottom plate act as the receiver chambers in a FDC. Screening of formulations is performed using pigskin as a model. The skin is sandwiched between the donor and receiver plates. The SC is exposed to the test formulations in the donor. The receiver wells are filled with phosphate buffered... 

Regardless of the lack of published data linking pH changes with freezing to loss of quality attributes of freeze-dried small molecules, the potential for significant changes exists, particularly with phosphate buffers. It is good formulation practice to minimize the concentration of buffers used, or eliminate them entirely if they are not needed. 

Murakami et al. [82] developed and validated a sensitive HPLC technique to quantify omeprazole in delayed release tablets. The analysis was carried out using a RP-Cig column with UV-VIS detection at 280 nm. The mobile phase was diluted with phosphate buffer (pH 7.4) and acetonitrile (70 30) at a flow-rate of 1.5 ml/min. The parameters used in the validation process were linearity, range, quantification limit, accuracy, specificity, and precision. The retention time of omeprazole was about 5 min with symmetrical peaks. The linearity in the range of 10-30 ng/ml presented a correlation coefficient of 0.9995. The excipients in the formulation did not interfere with the analysis and the recovery was quantitative. Results were satisfactory and the method proved to be adequate for quality control of omeprazole delayed-release tablets. 

Bonato and Paias [136] developed two sensitive and simple assay procedures based on HPLC and capillary electrophoresis for the enantio-selective analysis of omeprazole in pharmaceutical formulations. Racemic omeprazole and (S)-omeprazole were extracted from commercially available tablets using methanol-sodium hydroxide 2.5 mol/1 (90 10). Chiral HPLC separation of omeprazole was obtained on a ChiralPak AD column using hexane-ethanol (40 60) as the mobile phase and detection at 302 nm. The resolution of omeprazole enantiomers by capillary electrophoresis was carried out using 3% sulfated /1-cyclodextrin in 20 mmol/1 phosphate buffer, pH 4 and detection at 202 nm. 

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