Kinetics of procaterol auto-oxidation in buffered acid solutions.

The kinetics of procaterol (1) degradation in buffered acidic solutions (pH 4-6) was investigated using an HPLC procedure. The effect of temperature and ferric ions on the reaction rate was estimated. In acidic solutions, 1 undergoes pseudo first-order degradation with an induction period. The first-order rate constant for degradation increased and the induction period decreased with an increase in pH. Ferric ions catalyzed the degradation reaction and decreased the induction period. At pH 6, the activation energy of the reaction was 34.5 kcal/mol/deg. The results of this study indicate that 1 in solution is more stable at acidic pH, in the absence of heavy metal ions, and protected from air.

IR spectrophotometric assay of carbachol solutions.

Carbachol ophthalmic solutions can be assayed by evaporating a measured volume, dissolving the residue in methanol, and scanning the carbonyl stretching frequency in an IR spectrophotometer using a cell with calcium fluoride windows. Methylcellulose and other formulation vehicle components do not interfere. The method is stability indicating with respect to hydrolysis. It affords a recovery of 99.5+/-0.51% (RSD).

Stability of diltiazem in acid solution.

A brief study of the stability of diltiazem was conducted at 70 degrees C in the pH range of 0.45 to 6.1 using polarimetry. Racemization did not occur. The hydrolysis rate of the acetate ester moiety was found to be slow, with a minimum in the pH-rate catenary at approximately pH 3.5. Where reaction products are known, photoelectric polarimetry has great advantages in speed, convenience, and cost compared with chromatographic methods for measuring rates of reaction of optically active analytes.

Selective photometric determination of betamethasone benzoate and other 21-hydroxycorticosteroids.

Condensation of the glyoxal obtained by cupric acetate oxidation of 21-hydroxycorticosteroids with acetous phenylhydrazine reagent affords a near UV chromophore. All of the tested corticosteroids, including triamicinolone acetonide, which gives low color yields in the Porter-Silber reaction and its Lewbart-Mattox modification, gave similar absorption maxima (362-370 nm) and molar absorptivities (epsilon = 17,000-20,500). Since corticosteroid 21-esters and oxidation products do not undergo the reaction, the assay method based on it is stability indicating for betamethasone benzoate and the other test compounds. Procedures are described for the assay of two topical betamethasone benzoate preparations and hydrocortisone and prednisolone tablets; recovery and precision data are given.

High-pressure liquid chromatographic assay of theophylline, ephedrine hydrochloride, and phenobarbital tablets.

An innovation high-pressure liquid chromatographic method is described in which theophylline, ephedrine hydrochloride (measured as benzaldehyde), and phenobarbital are determined simultaneously with butabarbital as the internal standard. Chromatographic conditions were selected to afford a pH sufficient for rapid oxidation of ephedrine and relatively high UV absorbance for the barbiturates and a detection wavelength near the maximum for benzaldehyde and the barbiturates and the minimum for theophylline. Chromatograms show peaks from iodate, theophylline, phenobarbital, butabarbital, and benzaldehyde, in order of increasing retention time, all within the dynamic range of a conventional recorder. Procedures are provided for the assay of conventional and sustained-action tablet formulations.

High-pressure liquid chromatographic assay of quinestrol tablets.

A specific assay for quinestrol was developed using high-pressure liquid chromatography. The estrogen was separated from tablet excipients on a chemically bonded hydrocarbon column utilizing acetonitrile-water as the mobile phase. Linearity studies were carried out using peak height measurements, and the detector response to the concentration of the steroid was confirmed. This procedure was rapid, accurate precise, and specific for the assay of the synthetic estrogen in the presence of formulation excipients and structurally similar estrogens.

Trace decomposition of selegiline. Use of worst-case kinetics for a stable drug.

A solution of selegiline hydrochloride reference standard, which contained no detectable impurities at the time of its preparation, was found by HPLC to contain a trace of a compound at the locus of methamphetamine when analyzed after 1 year. Heating selegiline solutions at pH 7 and 105 degrees C produced methamphetamine as the major product at a rate which closely followed the first-order rate equation. Using only these data and worst-case assumptions, rate constants were estimated at various temperatures; the activation energy was estimated to be about 25 kcal, and the stability-indicating validity of the assay used was reaffirmed. Selegiline undergoes degradation at a negligibly slow rate.

Selective assay of benzoyl peroxide in lotions and creams.

A selective titrimetric method for the determination of benzoyl peroxide in lotions and creams was developed. It is based on the work of Horner and Jürgens, in which diacylperoxides, dialkylperoxides, peracids, and alkylhydroperoxides can be determined selectively by iodometry and acidimetry. The proposed assay is stability indicating with respect to peracids. Good recovery data were obtained.

Dissolution testing of nitroglycerin tablets.

The available types of dissolution testing apparatus for tablets and capsules are inapplicable to sublingual tablets, since these tablets are formulated to release their drug content within minutes in a small volume of fluid. A simple dissolution test method was developed for nitroglycerin tablets based on the reduction of nitroglycerin at a rotating platinum electrode, which provides reproducible stirring. The system provides instantaneous and continuous measurement of dissolved nitroglycerin in a small constant volume of buffered isotonic sodium chloride solution over a period of seconds to several minutes, when reduction is complete as shown by the current-time curve. Since the height of the curve is directly proportional to the amount of nitroglycerin in solution, the method also can be used to determine the drug content of individual tablets.

Stabilized compressed nitroglycerin tablets.

A stabilized compressed nitroglycerin tablet, containing microocrystalline cellulose NF and providone NF as stabilizing agents, was formulated. Bioavailability and physical tests were conducted on the compressed tablet and two leading brands of molded tablets. There was no difference in the mean pulse rate between a molded tablet formulation and the compressed tablet in a crossover study using 10 human volunteers and three tablet strengths, 0.3, 0.4, and 0.6 mg. The compressed tablet was most uniform when tested according to the USP method for weight variation and content uniformity. Various tests for nitroglycerin loss due to volatility, i.e., open dish test, thermogravimetric analysis, and simulated in-use test, all indicated that the stabilized compressed tablet was substantially more stable than partially stabilized or unstabilized molded tablets.