Pharmaceutical systems buffers

G. L. Flynn. Buffers pH control within pharmaceutical systems. J. Parent. Sci. Technol. 34 139-162, 1980. 

Other pharmaceutically relevant buffer systems have not been as well characterized as phosphate with respect to pH changes accompanying freezing. Larsen (13) reported that acetate, citrate, glycine, and Tris show only small pH shifts upon freezing. 

There seems to be no limit to the types of pharmaceutical systems that can be isolated in the amorphous state. In the literature, samples of sugars, acids, bases, polymers, buffers, inorganics, salts, natural products, proteins, and low-molecular-weight APIs have all been reported to exist in an amorphous form. Likewise, pharmaceutical raw materials, intermediates, and final products that include these amorphous materials are widespread and varied (Table 1). 

Off-line precipitation of captopril in pharmaceuticals using the Cu(II)-SCN system buffered at pH 5 gives a suspension to be injected into a buffered carrier that is transferred to a conical filter packed with cotton, and further diluted in the excess Cu(II) in a mixer prior to air/acetylene flame AAS. Systems analogous to online precipitation-dissolution can be found for saccharinate in pharmaceuticals Co, Ni, and Cd in urine and inmunoglobulin G in serum. 

Favaro and Fiorani [34] used an electrode, prepared by doping conductive C cement with 5% cobalt phthalocyanine, in LC systems to detect the pharmaceutical thiols, captopril, thiopronine, and penicillamine. FIA determinations were performed with pH 2 phosphate buffer as the carrier stream (1 mL/min), an injection volume of 20 pL, and an applied potential of 0.6 V versus Ag/AgCl (stainless steel counter electrode). Calibration curves were developed for 5-100 pM of each analyte, and the dynamic linear range was up to approximately 20 pM. The detection limits were 76, 73, and 88 nM for captopril, thiopronine, and penicillamine, respectively. LC determinations were performed using a 5-pm Bio-Sil C18 HL 90-5S column (15 cm x 4.6 mm i.d.) with 1 mM sodium 1-octanesulfonate in 0.01 M phosphate buffer/acetonitrile as the mobile phase (1 mL/min) and gradient elution from 9 1 (held for 5 min) to 7 3 (held for 10 min) in 5 min. The working electrode was maintained at 0.6 V versus Ag/AgCl, and the injection volume was 20 pL. For thiopronine, penicillamine, and captopril, the retention times were 3.1, 5.0, and 11.3 min, and the detection limits were 0.71, 1.0, and 2.5 pM, respectively. 

As yet, the number of applications is limited but is likely to grow as instrumentation, mostly based on existing CE systems, and columns are improved and the theory of CEC develops. Current examples include mixtures of polyaromatic hydrocarbons, peptides, proteins, DNA fragments, pharmaceuticals and dyes. Chiral separations are possible using chiral stationary phases or by the addition of cyclodextrins to the buffer (p. 179). In theory, the very high efficiencies attainable in CEC mean high peak capacities and therefore the possibility of separating complex mixtures of hundreds of... 

Buffers contain mixtures of weak acids and their salts (i.e., the conjugate bases of acids), or mixtures of weak bases and their conjugate acids. Typical buffer systems used in pharmaceutical dosage forms include mixtures of boric acid and sodium borate, acetic acid and sodium acetate, and sodium acid phosphate and disodium phosphate. The reason for the buffering action of a weak acid, HA (e.g., acetic acid) and its ionized salt, A" (e.g., sodium acetate) is that A" ions from the salt combine with the added hydrogen ions, removing them from solution as undissociated weak acid. 

Figure 3.9 Measurement of the enantiomeric purity of the pharmaceutical intermediate SB-240093 using CD-modified CE. The electropherogram shows the analysis of the chiral system suitability standard containing 0.5% w/w of the R-enantiomer. (Conditions PVA-coated fused silica capillary, 50 cm effective length, 57 cm total length, 50 pm i.d. buffer sodium phosphate [pH 7.0, 100 mM] containing 1.75 mM dimethyl-/l-CD voltage —30 kV [reversed polarity] temperature 20°C detection UV at 200 nm sample preparation 0.5 mg/ml in water DMSO (95 5, v/v) sample introduction 6 s at 35 mbar, capillary inlet at cathode.)...

Buffer solutions that are isosmotic with respect to some standard, typically chosen such that suspended cells will neither shrink nor expand. Sodium chloride solutions (0.90% weight/volume or 0.155 M) at 37°C is often used to represent physiological conditions. These buffer systems are also important in studies of intact cells and membranal organelles likewise, many pharmaceutical formulations must be prepared as isotonic solutions. Most enzyme-catalyzed reactions are affected by ionic... 

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