Monitoring radiolabelled antacid preparations in the stomach

Radiolabelled antacid preparations have been monitored in the stomach using gamma scintigraphy. The stomach contents were labelled with technetium-99m and two antacid preparations with indium-113m. It has been shown that the antacid containing aluminium hydroxide and magnesium oxide mixed and emptied with the other stomach contents. An alginate containing preparation tended to float on the food and emptied only slowly from the stomach.     

Studies of neutralizing properties of antacid preparations. Part 5: Dissolution kinetics of dihydroxyaluminum aminoacetate

The acid dissolution process of dihydroxyaluminum aminoacetate (1) has been studied by pH-stat method. The neutralization reaction was examined by monitoring the appearance of aluminum ion and aminoacetic acid in the reaction medium. The Weibull distribution function was applied to the quantitative interpretation of neutralization rate data. The mechanism of acid neutralization of 1 is discussed.     

Current problems in the quality control of pharmaceutical preparations manufactured in pharmacies II. Paracetamol contraining preparations

In our previous paper identification methods using chemical reactions and TLC are described for the active ingredients of pharmaceutical preparations in Formula Normales (FoNo VII.). Present paper introduces the development and validation of analytical methods suitable for quantitative determination of paracetamol containing dosage forms in FoNo VII. Titrimetric methods, UV spectroscopy and HPLC are used for assay of paracetamol and accompanying components (e.g. codeine, papaverine, caffeine and acetylsalicylic acid) in these preparations.     

Stability of nizatidine in extemporaneous oral liquid preparations

The stability of nizatidine in extemporaneous oral liquid preparations stored at room and refrigerated temperatures was studied. Preparations containing nizatidine in a final concentration of approximately 2.5 mg/mL were made by mixing the contents of a 300-mg nizatidine capsule with commercial juices (Gatorade, Stokely-Van Camp; Cran-Grape, Ocean Spray; apple juice, Sundor Brands; and V8 vegetable juice, Campbell Soup) and with aluminum hydroxide-magnesium hydroxide suspension (Maalox, Rorer). A control solution was prepared in water. Samples of each preparation were stored at 15-30 degrees C and at 5 degrees C. Initially and after 4, 8, 24, and 48 hours of storage, the samples were visually inspected, tested for pH, and analyzed in triplicate by high-performance liquid chromatography for nizatidine content. No appreciable changes in appearance or pH occurred. The only extemporaneous preparations with greater than 10% loss of nizatidine potency at 48 hours were the Cran-Grape and V8 preparations at room temperature. There was no correlation between pH of the preparations and changes in drug concentration. In the Maalox and V8 preparations, the drug powder did not dissolve uniformly. In all the preparations tested, nizatidine was stable for at least eight hours at refrigerated and room temperatures. In all except the Cran-Grape and V8 preparations, the drug was stable for 48 hours under both storage conditions.     

Studies of neutralizing properties of antacid preparations. Part 4: Application of Weibull distribution function to neutralization of dihydroxyaluminum sodium carbonate

The rate of neutralization of hydrochlorid acid by dihydroxyaluminum sodium carbonate (DHASC) has been studied by pH-stat method. The neutralization process was examined by monitoring the appearance of aluminum and sodium ions in the reaction medium. The Weibull distribution function was applied to the quantitative interpretation of neutralization rate data. All mathematically meaningful parameters derived from this distribution function were useful for consideration of the mechanism according to which the neutralization of DHASC occurs.     

微生态制剂的安全性及其临床应用

微生态学是一门研究微生物和宿主相互关系的生命科学分支。近年,由于微生态学的发展涌现出许多微生态制剂。它可调节微生态失调,保持微生态平衡,提高宿主健康水平。微生态制剂包括益生菌（活菌）、益生元（不为宿主消化的食物成分）及合生元（益生菌和益生元的混合物）三类。它适用于腹泻（包括儿童腹泻、抗生素相关性腹泻及旅行者腹泻等）、肠易激综合征、炎症性肠病、幽门螺旋杆菌感染、便秘、肝硬化、过敏及女性泌尿生殖道感染等疾病。微生态制剂相对比较安全;但免疫力低下及肠道黏膜屏障受损的患者应避免使用活菌制剂以免发生机会感染。使用这类制剂时一般应注意以下几方面：①用〈40℃温开水送服;②活菌制剂避免与铋剂、鞣酸、活性炭、酊剂及某些抗生素同服;③低温避光贮存。     

In vitro and in vivo defoaming action of three antacid preparations

The defoaming activity of three tablet antacids (hydrotalcite, hydrotalcite/dimethicone and aluminium hydroxide/dimethicone) powdered to 60 mesh was measured in vitro using a new static/dynamic technique. Their antacid actions and that of aluminium hydroxide gel B.P.C. were also measured using a modified Fuch's test. Combination of dimethicone with hydrotalcite conferred good defoaming activity with little effect on pH profile whilst combination of aluminium hydroxide with dimethicone markedly altered both. Additionally, the defoaming actions of the three commercial antacids were assessed in vivo. Radiographs were taken after administration of antacid, a foaming mixture and a normal barium meal. The radiographs were then ranked blind by 5 radiologists. The rankings assigned the significantly greatest (Mann-Whitney U-test) defoaming effect to the hydrotalcite/dimethicone combination, there being no difference between the other two preparations. The in vitro results were thus confirmed.     

The bioavailability of combination preparations of acetylsalicylic acid and codeine phosphate

Plasma levels time curves of acetylsalicylic acid, salicylic acid, salicyluric acid and codeine were monitored after intravenous, oral and rectal application (single dose) of preparations containing acetylsalicylic acid and codeine. The mean absolute bioavailability of acetylsalicylic acid was 68% after oral application and 60% after rectal application. The corresponding bioavailability data of codeine were 59% and 63%, respectively.     

In vitro acid reactivity of three commercial antacid tablets.

The in vitro acid reactivity of three commercial brands of aluminum and magnesium hydroxide antacid tablets was determined by two methods. A pH-stat test was used to examine the rate and extent of acid neutralization at a constant pH of 3.0. A modified Rossett-Rice test was used to record the length of time during which the antacid products maintained the pH of a simulated gastric solution at between 3.0 and 5.0. Acid neutralization by product A was faster and more complete than that by product B or C. The percent of theoretical acid consuming capacity at 30 minutes of product A (86.8%) was significantly greater than that of product B (56.1%) and product C (57.0%) tablets. The 32-minute Rosett-Rice time A was significantly longer than the 16- and 12-minute times of products B and C, respectively. The differences observed may be attributed to different reactivities of the raw materials used in the products, or formulation and processing variables. It is not known how the data relate to in vivo performance.     

Kinetic spectrophotometric determination of nizatidine and ranitidine in pharmaceutical preparations.

A new simple and sensitive kinetic spectrophotometric method is described for analysis of nizatidine (I) and ranitidine (II). The method involves the reaction of the drugs with alkaline potassium permanganate, whereby a green color peaking at 610 nm is produced. The reaction is monitored spectrophotometrically by measuring the rate of change of absorbance of the resulting manganate species at 610 nm. Calibration graphs are linear over the concentration range 0.8-4.0 microg/ml and the precision (% RSD 1.80, 1.53 for I and II, respectively) is quite acceptable. The method is satisfactorily applied for direct analysis of pharmaceutical preparations containing I and II. A proposal of the reaction pathway is postulated.     

Comparative analysis of the vagal stimulation of gastric acid secretion in rodent isolated stomach preparations.

1. Electrical field stimulation produced a tetrodotoxin-sensitive, frequency-dependent, release of acid from isolated, lumen-perfused, stomach preparations from mouse, immature rat and guinea-pig. 2. In the guinea-pig and mouse preparations, the frequency-dependent response was abolished by hexamethonium, acetylcholine (ACh) muscarinic (M) and histamine H2-receptor blockade, consistent with the hypothesis that the vagal ACh acts indirectly by stimulating the release of endogenous histamine. 3. In contrast, in the rat preparation the frequency-dependent response was partially refractory to all of these inhibitors. However, a combination of H2- and ACh M-receptor blockade did abolish the effect. 4. We conclude that vagal-stimulated acid secretion in the rat, unlike the other two species, behaves as though there is a direct innervation of the oxyntic cells by either cholinergic or noncholinergic neurones.     

Microbial viability in preparations packaged for single use

We evaluated microbial viability in preparations packaged for single use only which mandate that residual solution be discarded such as albumin and globulin preparations as blood products, preparations containing albumin (such as urokinase and interferon), fat emulsions, and a preparation containing fat emulsions (propofol). In most preparations, Serratia marcescens and Burkholderia cepacia proliferated rapidly at 30 degrees C. However, in globulin preparations containing 1-2.25% glycine to prevent protein degradation (Gamma-Venin P, Venilon-I, Globulin Injection, and Ahlbulin), no growth of S. marcescens and B. cepacia was detected over 24 h at 30 degrees C. For globulin preparations containing 1-2.25% glycine, the injunction to "Discard residual solution after the package has been used" in the package inserts can be revised to "It is possible to use residual solution within 24 h after the package has been used with storage in a cool place."     

Chemical characterization of iron (III)-hydroxide-dextrin complexes. A comparative study of commercial preparations with alleged reproductions used in the examination of bioavailability

The iron (III)-hydroxide-dextrin complexes in two commercial preparations were compared with alleged reproduction which have been prepared for bioavailability studies published recently. Precipitation behaviour in chloride media, kinetics of reduction by ascorbic acid, magnetic susceptibility and laser light scattering data reveal that the original preparations and the alleged reproductions are neither identical nor equivalent in chemical properties. The historical controversy about iron(II) versus iron(III) preparations in oral therapy should be dropped because, on chemical grounds, iron(II) salts are sources of iron(III) species appearing in the gastro-intestinal tract.     

Comparative review of topical ophthalmic antibacterial preparations

The choice of an antibacterial is based on considerations of pharmacodynamic, pharmacokinetic and bacteriological characteristics, risk of selecting resistant mutants, and cost. In this article we review 16 commercially available ophthalmic antibacterial preparations. Fusidic acid and bacitracin are selective for gram-positive bacteria whereas polymyxin B targets gram-negative species. Aminoglycosides and quinolones are broad spectrum antibacterials. The widespread use of an antibacterial increases risks of selecting resistance to it. Acquired resistance is well documented for fusidic acid and rifamycin, and newly described for quinolones. The bioavailability of an antibacterial agent depends on the target bacterial species, the site of infection and the integrity of the haemato-aqueous barrier. Some agents (fusidic acid, quinolones) penetrate the cornea, passing into the anterior chamber of normal eyes at therapeutic concentrations, whereas others (polymixin B, bacitracin) have no penetrating powers and remain at the surface of the eye. Toxicity is mostly manifested by allergic reactions to excipients or active ingredients in topical antibacterial preparations. A few cases of haematological toxicity have brought suspicion on topical chloramphenicol, but the link has yet to be proven. Erythromycin and polymyxin B are probably okay to use as topical applications in pregnant women and nursing mothers. Costs of treatment must be evaluated as a whole (regimen, drug associations). Prices for a bottle of eyedrops may vary 3-fold. The cheapest drugs include chloramphenicol, polymyxin B and gentamicin, the most expensive being fusidic acid and the quinolones.     

Pharmacokinetics of preparations of lipoic acid and their effect on ATP synthesis, processes of microsomal and cytosol oxidation in hepatocytes in liver damage in man

The features of the pharmacokinetics of preparations of alpha-lipoic acid (lipoic acid, thioctacide) as compared with their pharmacodynamic effects were studied in 125 patients with chronic diffuse diseases of the liver of viral and alcohol etiology. After a single administration of the preparations, the authors found an elevation of the maximal blood concentrations and an increase of alpha-lipoic acid elimination half-life in patients with liver cirrhosis as compared with chronic hepatitis patients. During the replacement therapy and elimination of alpha-lipoic acid deficiency by using the preparations containing lipoic acid, there is commonly an increase ATP content, an elevation of functioning mass of hepatocytes and activation of liver detoxifying function according to the data of the tests of galactose cytosol oxidation, microsomal oxidation of antipyrine and conjugation of bilirubin.     

The biotransformation of allyl alcohol and acrolein in rat liver and lung preparations

The biotransformation of allyl alcohol and acrolein by rat lung and liver preparations was investigated by measuring acrolein, acrylic acid, glycidol, and glycidaldehyde. Acrolein was detected by high-pressure liquid chromatography from incubation mixtures containing allyl alcohol, NAD+, and liver 9000g supernatant fraction or cytosol. Acrolein was not formed when lung fractions were treated similarly. Addition of pyrazole in the incubation mixture inhibited the reaction. The metabolism of acrolein to acrylic acid by liver 9000g supernatant fraction, cytosol, and microsomes has been demonstrated; acrylic acid formation was greater with NAD+ than with NADP+ in all three fractions. Acrylic acid was also formed from allyl alcohol. Disulfiram inhibited the NAD+- and NADP+-dependent reactions. Acrylic acid was not formed when lung preparations were used. Lung and liver microsomal epoxidation products of allyl alcohol and acrolein have been identified. Conversion of glycidol to glycerol and glycidaldehyde to glyceraldehyde by liver epoxide hydrase has been demonstrated. Epoxides, glycidol, and glycidaldehyde were also found to be substrates for lung and liver cytosolic glutathione S-transferase.     

Enhancing fluidity of concentrated antacid suspensions.

Highly concentrated antacid suspension can by fluidized by adding a colloidal polyelectrolyte to alter the charge on antacid particles from positive to negative. A deflocculated state is assumed to exist in such preparations, as supported by electrophoretic and viscometric analyses. When viscosity is directly correlated with the zota-potential, viscometry becomes particularly useful in confirming that the suspension has been maximally fluidized.     

Benefit vs. risk of oral aluminum forms: antacid and phosphate binding vs. absorption

Oral consumption of aluminum (Al) compounds to neutralize stomach acid and bind phosphate can result in Al absorption and potential Al accumulation and toxicity. Selecting an effective antacid/phosphate binder would optimize the benefit/risk of therapy. It has been suggested that Al solubilization would predict oral Al bioavailability, and therefore risk. The acid neutralizing and phosphate binding capacity of eight representative Al forms was determined. The results were compared to the oral bioavailability, solubility and octanol/water partitioning coefficient of each compound. The results fail to confirm Al solubilization as an indicator of Al absorption, and presumably, Al toxicity. Acid neutralizing and phosphate binding capacities did not correlate with bioavailability, solubility or the partitioning coefficient. Determination of acid neutralization and phosphate binding in vitro and Al absorption and/or toxicity in vivo may be more predictive measures to establish the benefit/risk ratio of Al-containing products.     

Preparation and evaluation of Eudragit gels. III: Rectal gel preparations for sustained release of pentoxifylline.

A novel method was established for the preparation of Eudragit S, Eudragit L, and Eudispert high-viscosity (hv) hydrogel and xerogel preparations containing a medicinal component such as pentoxifylline (an agent that improves cerebral microcirculation). A significant correlation was found between the in vitro mean dissolution time and the in vivo mean residence time of pentoxifylline after rectal administration of these preparations in rabbits. Staying properties of the hydrogel and xerogel preparations in the lower part of the rectum were compared with those of polyethylene glycol 2000 and Witepsol S-55 suppositories in rats, with water-insoluble dye. Eudispert hv hydrogel and xerogel preparations have excellent staying properties in the rectum. The efficacy of Eudispert hv xerogel preparations may be reduced by first passage through the liver after oral administration.     

Current problems in the quality control of pharmaceutical preparations manufactured in pharmacies III. Investigation of theophilline containing suppositories

In the present part of our series of papers a study on theophilline containing suppositories prepared in pharmacies is described. From the possible methods for assay of theophilline two nonaqueous titrations are compared. In first, theophilline is measured as a very weak base in a mixture of glacial acetic acid and acetic anhydride with perchloric acid using Sudan-III indicator, in second, the compound is measured as medium strong acid in dimethylformamide solvent with sodium-hydroxide titrant using phenolphtalein indicator. These methods were validated and the first was found more appropriate for regulatory control. We investigated suppositories prepared in our laboratory and in different pharmacies. The study revealed the poor quality of the preparations due to the difficulties in the technology and the importance of the applied vehicle. A guideline for the good preparation practice and an alternative technology are proposed.