[Stability of oxyethyltheophylline solutions for injection]. / Zur Stabilität von Oxyethyltheophyllin-Injektionslösungen.

The testing of oxyethyltheophylline solutions for injection involved the separate study of their constituents, theophylline and ethophylline, particular attention being given to the behaviour of both these active agents under thermal stress in acid or alkaline medium. Acids exert little effect on the stability. In contrast to theophylline, ethophylline is rapidly decomposed by alkaline hydrolysis into two degradation products. The preparative production of ethophyllidine evidenced that ethophylline is decomposed under alkaline stress, via ethophyllidinecarboxylic acid (not isolated), to the heretofore unknown ethophyllidine (unequivocally characterized by analysis), which is the major cause of the instability of oxyethyltheophylline solutions for injection.

[Analysis and stability of atropine sulfate and scopolamine hydrobromide. 3: Studies on the stability of tropane alkaloids; 80: contribution to problems in the use of plastic containers for liquid pharmaceuticals]. / Zur Analytik und Stabilität von Atropinsulfat und Scopolaminhydrobromid.

On evaluating their investigations, the authors discuss the degradation mechanism of tropane alkaloids in aqueous solution. As evidenced by competitive and consecutive reactions (hydrolysis, dehydration, dimerization), the degradation mechanism is characterized by a complicated course. Apart from temperature, a series of other factors, above all the pH value, exerts a considerable effect on the stability of both the alkaloids. Unbuffered solutions are more stable than buffered ones. The isothermal short-time test is not suitable for stability prediction. In the long-time test it was found that unbuffered aqueous atropine sulphate solutions still contained 90% of their initial drug content after 18 months' storage in low-density polyethylene containers at 20 degrees C. Scopolamine hydrobromide solutions showed an almost analogous behaviour. Of the container materials tested, low-density polyethylene bottles have been found to be best suited.

[Analysis and stability of suxamethonium chloride. 2: Study of various factors in the stability of suxamethonium chloride injection solutions]. / Zur Analytik und Stabilität von Suxamethoniumchlorid. Teil 2: Untersuchung einiger Faktoren auf die Stabilität von Suxamethoniumchlorid-Injektionslösungen.

The packing material (glass ampoules and plastic disposable syringes) and the degree of purity of the active agent do not affect the stability of injectable suxamethonium chloride solutions. In contrast to this, the stability was markedly improved by lowering the temperature of storage. Injectable suxamethonium chloride solutions may be stored in plastic disposable syringes.

[Analysis and stability of atropine sulfate and scopolamine hydrobromide. 2. Quantitative determination of the alkaloid in its decomposition product; 79. contribution to problems concerning the use of plastic containers for liquid pharmaceuticals]. / Zur Analytik und Stabilität von Atropinsulfat und Scopolaminhydrobromid. Teil 2: Quantitative Bestimmung der Alkaloide neben Zersetzungsprodukten; 79. Mitteilung: Beiträge zur Problematik des Einsatzes von Kunststoffbehältern für flüssige Arzneizubereitungen.

The authors describe a method which permits, after thin-layer chromatographic separation and elution by means of the Eluchrom apparatus, to determine the tropane alkaloids and apoatropine in the presence of their decomposition products using tropaeolin 00. The recommended method has proved to be superior to other elution variants with regard to accuracy and reproducibility. Detectable amounts (microgram/ml): atropine, 0.4-4.0; scopolamine, 1.2-7.2; apoatropine, 0.8-3,2.

[Analysis and the stability of codeine phosphate. 2: Stability of aqueous codeine phosphate solutions]. / Zur Analytik und Stabilität von Codeinphosphat. 2: Stabilität von wässrigen Codeinphosphatlösungen.

The degradation velocity of aqueous codeine phosphate solutions is of first order. The formation of the degradation products (isomerization products) depends upon temperature, light and pH value. At pH = 3.5, codeine phosphate solutions are relatively stable. Atmospheric oxygen exerts no effect. Of the complexing agents and antioxidants tested, only citric acid and thiourea seem to be capable of reducing the rate of degradation. Besides glass ampoules, plastic containers of low-density polyethylene proved to be suited for codeine phosphate solutions.

[Stability of cyclodrin hydrochloride. 3: Stability of cyclodrin hydrochloride as a substance and in ophthalmologic solutions. 51: Contributions to problems concerning the use of plastic receptacles for liquid pharmaceuticals]. / Beitrag zur Stabilität des Cyclodrinhydrochlorids. Teil 3: Stabilität des Cyclodrinhydrochlorids als Substanz und in ophthalmologischen Lösungen. 51. Mitteilung: Beiträge zur Problematik des Einsatzes von Kunststoffbehältern für flüssige Arzneizubereitungen.

The authors deal with the stability of cyclodrin hydrochloride. A reference sample of solid cyclodrin hydrochloride stored for four and a half years showed 0.4-0.6% degradation. A storage stability of five years is considered justifiable. In eye-drops the stability of this active agent is determined by the pH value. Unbuffered eye-drops (optimized formula) are considerably more stable than the buffered solutions hitherto used. Unbuffered eye-drops contained in glass bottles as well as in plastic bottles should be stable for 2-3 years.

[Analysis and stability of suxamethonium chloride. 1. Detection and quantitative determination of the intact active agent with its degradation products]. / Zur Analytik und Stabilität von Suxamethoniumchlorid. Teil 1: nachweis und quantitative bestimmung des intakten wirkstoffs neben zersetzungsprodukten.

The authors developed methods permitting to follow the course of degradation in injectable solutions of suxamethonium chloride. The qualitative detection of the active agent in the presence of degradation products is achieved by thin-layer chromatography and spraying with Dragendorff's reagent and bromocresol green indicator solution. The same separation technique may be used for determining with sufficient accuracy the intact agent in the eluate, using the method of Okken and Haas. Furthermore, a modified Draganic procedure (which is based on the spectrophotometric determination of the hydrolysis products succinic acid monocholine chloride and succinic acid as a Cu-benzidine complex) is suited for estimating the degree of degradation. No previous separation is required because the molar extinction efficients of the monoester and of the acid are in agreement, so that the degree of degradation can be calculated from the sum of the molar concentrations. The value of these methods is demonstrated by analyzing experimental mixtures of the intact agent and degradation products.

[Analysis and stability of atropine sulfate and scopolamine hydrobromide. 1. Qualitative detection of alkaloids in the presence of their decomposition products. 73. Contribution to the problem of the use of plastic receptacles for liquid pharmaceuticals]. / Zur Analytik und Stabilität von Atropinsulfat und Scopolaminhydrobromid. Teil 1: Qualitativer Nachweis der Alkaloide neben Zersetzungsprodukten. 73. Mitteilung: Beiträge zur Problematik des Einsatzes von Kunststoffbehältern für flüssige Arzneizubereitungen.

The authors deal with the qualitative determination of tropane alkaloid salts (atropine sulphate and scopolamine hydrobromide) in aqueous solutions in the presence of their decomposition products using thin-layer chromatography. Aqueous solutions of these tropane alkaloid salts were tested for stability after storage in glass and polyethylene containers under various conditions (pH value, temperature, ultra-violet irradiation, oxidative effects). Besides tropine, apoatropine, alpha- and beta-belladonine, further decomposition products showing a basic reaction (and in part not yet identified) were detected. The stability of solid atropine sulphate was studied by means of differential thermal analysis and mass spectrometry.

[On the antimicrobial activity of benzalkonium chloride in potential contact lens fluids]. / Zur antimikrobiellen Wirksamkeit von Benzalkoniumchlorid in potentiellen Kontaktlinsenflüssigkeiten.

To assess the suitability of benzalkonium chloride as a preserving agent for potential contact lens fluids, the authors tested its antimicrobial efficiency at various pH values, in the presence of viscosity modifiers (hydroxyethylcellulose, polyvinylpyrrolidone, polyacrylamide) and also in combination with other preserving agents. The diffusion test and the suspension test were used as test methods. The efficiency of benzalkonium chloride depends upon the pH value of the solution and upon the concentrations of the viscosity modifiers. No better results were achieved by combination with phenylethanol and chlorobutanol. Formulations for potential contact lens fluids were indicated, the appropiateness of which is viewed in microbiological perspective.

[On the stability of phenylmercury salts. Part 50: Contributions to problems concerning the use of plastic receptacles for liquid pharmaceuticals (author's transl)]. / Zur Stabilität der Phenylquecksilbersalze. 50. Mitteilung: Beiträge zur Problematik des Einsatzes von Kunststoffbehältern für flüssige Arzneizubereitungen.

The authors describe a dithizone method for the determination of phenylmercury salts that yields easily reproducible results on examining the stability of these preserving agents. Aqueous solutions of phenylmercury salts are instable already in glass bottles, but they are instable to a much greater extent in low-density polyethylene bottles. Their degradation is accelerated in the presence of chloride ions. When stored under nitrogen, the phenylmercury salt solutions show lower losses of preserving agents than when stored under normal air. The ultra-violet extinction of phenylmercury salt solutions increases during storage in glass bottles, and decreases during storage in plastic bottles. In plastic bottles, the degradation is associated with sorption.

[Contribution to the stability of tropicamide solutions (author's transl)]. / Beitrag zur Stabilität von Tropicamidlösungen.

The course of the degradation of tropicamide solutions was elucidated. Thus, inter alia, intramolecular elimination of water leads to a compound comparable to apoatropine that the authors designated by atropicamide. Furthermore, methods are described that permit (after thin-layer chromatographic repartition) to detect and to determine quantitatively the active principle in the presence of its degradation products. Tropicamide is stable in aqueous solution; eye-drops prepared from such a solution (Mydrum) are stable for no less than 5 years.

[The effect of the gas permeability of plastics on the stability of thiomersal. Part 49: Contributions to problems concerning the use of plastic receptacles for liquid pharmaceuticals (author's transl)]. / Einfluss der Gaspermeabilität von Kunststoffen auf die Stabilität des Thiomersals. 49. Mitteilung: Beiträge zur Problematik des Einsatzes von Kunststoffbehältern für flüssige Arzneizubereitungen.

Our studies have shown that the considerable losses of Thiomersal contained in low-density polyethylene bottles are not attributable, as suggested in the literature, to a sorption of this preserving agent. Intact Thiomersal is not sorbed by low-density polyethylene; on the contrary, the good permeability of this packing material to gas, especially oxygen, accelerates the degradation of Thiomersal. Furthermore, the ethylmercury resulting from this degradation is able to permeate through low-density polyethylene by which a displacement of the reaction equilibrium takes place in favour of the degradation products, and the degradation of Thiomersal is accelerated. The mechanism of the degradation of Thiomersal in the presence of oxygen was elucidated.

[Contribution to the stability of papaverine. Part 6: The stability of aqueous solutions of papaverine hydrochloride (author's transl)]. / Beitrag zur Stabilität von Papaverin. Teil 3: Stabilität von wässrigen Papaverinhydrochloridlösungen.

It is dealt with the storage stability of aqueous solutions of papaverine hydrochloride in glass and plastic vials. The effects of pH value, light, protective gassing, complexing agents and antioxidants were investigated. It was found that solutions stored in glass vials degraded in a less degree than solutions kept in plastic vials.

[On the analytics and the stability of aminophenazone. Part 1: Detection and determination of aminophenazone in the presence of its decomposition products (author's transl)]. / Zur Analytik und Stabilität von Aminophenazon. Teil 1: Nachweis und Bestimmung des Aminophenazons neben Zersetzungsprodukten.

It is dealt with the decomposition of aminophenazone in aqueous solutions. The mechanism of decomposition of aminophenazone is discussed in the light of results obtained from model oxidations, and their importance in short-time tests is pointed to. The decomposition products were separated and detected by thin-layer chromatography. The authors succeeded in using a known method for the direct quantitative determination of aminophenazone in stored decomposed solutions.

[Contribution to the stability of papaverine. Part 2: Quantitative determination of papaverine in the presence of degradation products (author's transl)]. / Beitrag zur Stabilität von Papaverin, teil 2(2): Quantitative Bestimmung des Papanerins neben Zersetzungsprodukten

With resort to the coralyne reaction the authors present a fluorometric method permitting to determine papaverine directly in the presence of papaverinol and papaveraldine. The standard deviation of the method is +/- 1.63.