Adsorption of paracetamol and chloroquine phosphate by some antacids.

The adsorption of paracetamol and chloroquine phosphate onto some antacids with adsorptive properties, has been studied. Dissolution of the drugs from commercial tablets was significantly retarded in the presence of the antacids. The adsorption and retardation of dissolution of both drugs by the adsorbent antacids studied followed the rank order magnesium trisilicate greater than magnesium oxide greater than aluminium hydroxide greater than edible clay. The concomitant administration of the drugs and antacid formulations containing any of these should be discouraged.     

In vitro adsorption of some corticosteroids on antacids

The adsorption of prednisone, prednisolone, fluprednisolone, betamethasone, triamcinolone, beta-methylprednisone acetate and hydrocortisone acetate on various antacids or adsorbents was studied at 37 degrees C. The antacids or adsorbents used were magnesium trisilicate, aluminum hydroxide, bismuth oxycarbonate, magnesium oxide, magnesium carbonate, calcium carbonate, talc, kaolin and charcoal. Magnesium trisilicate and charcoal had the highest adsorption capacity for the corticosteroids tested. Bismuth oxycarbonate and talc had intermediate adsorption properties while kaolin and aluminium hydroxide had lower effects. Other antacids were without any adsorption character. Results of the elution study confirmed the higher affinity of magnesium trisilicate over that of bismuth oxycarbonate and talc for the steroids tested. Further in vivo testings are still needed to assess the effect of antacids on the bioavailability of coadministered corticosteroids.     

The in vitro adsorption of some antibiotics on antacids.

The adsorption of oxytetracycline hydrochloride, tetracycline hydrochloride, doxycycline hyclate, triacetyloleandomycin, chloramphenicol, ampicillin, and cloxacillin sodium was studied on various antacids namely, magnesium trisilicate, magnesium oxide, calcium carbonate, bismuth oxycarbonate, aluminium hydroxide, and kaolin. The adsorption of the various antibiotics by milk was also tested as milk is frequently used as an antacid. Charcoal was included in the present study as a model adsorbent having a large hydrophobic surface. The adsorption of the various antibiotics on the different antacids and other adsorbents in most cases obeyed the Freundlich adsorption isotherm. Magnesium trisilicate and magnesium oxide showed the highest adsorptive capacity, relative to other antacids used, for most antibiotics. Calcium carbonate and aluminium hydroxide and intermediate power while kaolin and bismuth oxycarbonate had the least adsorptive power. Charcoal exhibited a marked adsorption for all antibiotics tested. Tetracyclines were found to be more highly adsorbed than other antibiotics studied. Triacetyloleandomycin and chloramphenicol had intermediate values. Ampicillin was only adsorbed to a slight extent while cloxacillin was not adsorbed on the antacids used. The extent of adsorption was correlated to the structure of both the adsorbent and adsorbate, the pH of the adsorbent suspension, and to the polarity of the antibiotic in such pH. The reversibility of the adsorption process was studied in different media and at pH values similar to those of the gastrointestinal tract. The extent of elution was found to be inversely proportional to the adsorptive capacity of the different adsorbents. In general, 0.0143 n NaHCO3 solution was found to possess higher eluting properties than 0.01 n HCl. An exception to this pattern was observed with tetracyclines adsorbed on aluminium hydroxide where the elution with acid resulted in a higher degree of desorption. Careful in vitro and in vivo testing of drug availability is advisable prior to the concomitant administration of antibiotics with antacids or other adsorbents.     

The uptake of digoxin and digitoxin by some antacids

The adsorption of digoxin and digitoxin by some antacids has been investigated. Magnesium trisilicate showed the highest adsorptive effect, the extent of adsorption being up to 99 % for the two glycosides. The calculated values of monolayer adsorption were 0·93 and 1·36 mg g-¹ for digoxin and digitoxin respectively. At 37° only partial elution of adsorbed glycosides occurred in 0·2N HCl due to re-adsorption on the hydrated silica gel formed. Antacid preparations containing magnesium trisilicate adsorbed digoxin from a paediatric elixir to the extent of about 95%. Dissolution of digoxin tablets was similarly affected since almost complete suppression of dissolution occurred in the presence of 0·5 g magnesium trisilicate per 0·25 mg digoxin tablet. The effect of antacids, when concurrently administered with oral digoxin, on the bioavailability of the drug, is discussed.     

In-vitro interaction of a novel immunosuppressant, FK 506, and antacids.

The effect of selected antacids on the amount of FK 506 in solution in simulated gastric juice has been studied. FK 506 (2.5 mg) was incubated in 100 mL simulated gastric fluid (SGF) with the equivalent of 500 mg of various antacids. The addition of Mylanta and Tums resulted in 14 and 30% loss of FK 506, respectively, in 24 h; 98% loss was observed in 12 h in the presence of Mag-Ox; 100% loss was observed in the presence of magnesium oxide powder in 2 h. The loss of FK 506 from these solutions appears to be due to a pH mediated degradation of FK 506. The addition of aluminium hydroxide gel USP (Roxane) to the FK 506 solution resulted in a 35% loss within 2 min but no further loss was noted for 24 h, indicative of adsorption of FK 506. These results suggest that until additional in-vivo studies are carried out, it is prudent not to dose FK 506 and antacids at the same time to avoid potential interactions.     

Pharmacokinetic interactions with digoxin

Numerous pharmacological agents have been shown to produce clinically significant pharmacokinetic interactions with digoxin. Drugs which reduce digoxin absorption include the antacids aluminium hydroxide, magnesium hydroxide and magnesium trisilicate, the antidiarrhoeals kaolin and pectin, the hypocholesterolaemic agent cholestyramine and the chemotoxins cyclophosphamide, vincristine and bleomycin. Certain antibiotics including sulphasalazine, neomycin and aminosalicylic acid reduce digoxin absorption while others, including erythromycin and tetracycline, increase the bioavailability of digoxin in some patients. Capsule preparations of digoxin in solution are less subject to several of the interactions which affect the absorption and bioavailability of digoxin tablets. Various drugs induce alterations in the volume of distribution and clearance of digoxin. Cardiac patients receiving digoxin therapy are particularly prone to interactions with commonly co-administered medications such as the antiarrhythmics quinidine and amiodarone, the calcium channel blockers verapamil and nifedipine, and possibly some vasodilating agents. Studies of digoxin interactions have yielded discrepant results, indicating the need for careful analysis of investigational design before arriving at clinical conclusions.     

The Heidelberg capsule, an antacid of improved galenics]

By means of the Heidelberg capsule the influence of two different antacids on the acidity of gastric juice was measured in 16 normal test subjects. The antacidic combination drugs were Roha salt tablets (RSTB) containing herba absinthii 1.9 mg; fruct. anisi 35.5 mg; rhiz. calami 22.2 mg; bolus alba 14.0 mg; calcium phosphoricum 53.3 mg; magnesium sulfuricum 41.1 mg; calcium carbonicum 70.0 mg; magnesium carbonicum 42.0 mg; sodium bicarbonicum 1120 mg, and Roha gastric tablets (RMTB) with retarded release and containing fruct. anisi 40 mg; herba absinthii 3.2 mg; calcium carbonicum 688 mg; sodium bicarbonicum 480 mg; magnesium carbonicum 40 mg. Compared to the simple antacid RSTB, the duration of the neutralizing effect of the retarded RMTB was prolonged significantly by 300%.     

Effects of antacids on the clinical pharmacokinetics of drugs. An update

Since a previous review by Hurwitz was published in 1977 a large number of reports on drug interactions with antacids have appeared, few of which are of clinical relevance. Tetracyclines form insoluble complex molecules by metal ion chelation with various antacids; tetracycline absorption may be decreased by more than 90% by this interaction. Of the new class of quinolone antibiotics, the absorption of ciprofloxacin and ofloxacin is reduced by 50 to 90% in the presence of aluminium- and magnesium hydroxide-containing antacids. In contrast to early work showing inhibition of the absorption of beta-adrenergic blocking drugs by antacids, subsequent studies did not confirm a reduction in the bioavailability of either atenolol or propranolol during antacid treatment; indeed, they showed an increase in the plasma concentrations of metoprolol when the drug was coadministered with an antacid. The bioavailability of captopril was significantly reduced in the presence of an antacid, and lower plasma concentrations of this angiotensin-converting enzyme inhibitor were accompanied by a reduction of its effect on the systolic blood pressure of the patients. The absorption of the cardiac glycosides digoxin and digitoxin is not inhibited by antacids to a significant degree, although earlier studies had shown a positive effect when the dissolution of the glycoside preparations was relatively poor. Antacids reduce the bioavailability of the H2-receptor antagonists cimetidine and ranitidine only when high antacid doses are used and when the drugs are administered simultaneously. The bioavailability of famotidine was not significantly altered by a potent antacid preparation, although a trend towards reduced absorption was observed. Iron absorption is significantly decreased in the presence of sodium bicarbonate and calcium carbonate, but is nearly complete when coadministered with aluminium-magnesium hydroxide. Nonsteroidal anti-inflammatory drugs such as naproxen, tenoxicam, ketoprofen, ibuprofen and piroxicam are not affected in their absorption by antacid treatment. Theophylline bioavailability is unchanged when the drug is given together with antacids, although its rate of absorption may be altered, leading to a reduction or an increase in the time of the occurrence of peak plasma drug concentrations.     

盐酸吗啡普通片及硫酸吗啡控释片在不同溶剂中溶释过程的对照研究

本文采用紫外分光光度法对国产盐酸吗啡普通片及合资厂产硫酸吗啡控释片于蒸馏水、人工胃液、人工肠液中进行体外溶出度和释放度测定。结果表明，两种片剂的溶释均符合中国药典９５版标准，控释片在人工肠液中溶释参数Ｔ５０、Ｔｄ、ｍ与在蒸馏水及人工胃液中的溶释参数差异具显著性（Ｐ＜０．０１），在人工肠液中的释放过程明显缓慢。     

钙铝混悬液对小鼠的抗腹泻作用及拆方分析

目的：考察钙铝混悬液的药 作用，并对其组方的合理性进行探讨。方法：制备麻油所致的小鼠腹淀动物模型，经口灌胃给药，２５ｍＬ．ｋｇ^-1和１２．５ｍＬ．ｋｇ^-1两剂量。结果：在腹淀动物模型上表现出明显的抗腹作用，并且抑制由麻油引起的小鼠小肠推进运动。以高剂量（２５ｍＬ．ｋｇ^-1）在腹淀模型上进行拆方分析，方剂中单味药物组方均未 表现出明显的抗腹淀作用，两味药物组方中除丁得罗勒油和三硅酸镁或碳酸钙的组方呈现抗     

Effect of pharmacotechnical design on the in vitro interaction of ketoconazole tablets with non-systemic antacids

In certain polytherapy programs, ketoconazole can be administered with some antacids that could modify its dissolution rate and reduce its absorption leading to therapeutic failures. The aim of this work was to evaluate the influence of some excipients on this interaction in vitro. In this way, six formulations of directly compressible ketoconazole tablets were developed. The results confirmed that the dissolution rate of ketoconazole tablets was significantly reduced in the presence of antacids. Nevertheless this interaction was remarkably avoided in some of the formulations checked and in some conditions. In this way, the inclusion of a disintegrant (sodium starch glycolate) not only increased the dissolution rate of ketoconazole in the tablets, as expected, but it also modified the degree in which the dissolution rate was decreased in the presence of antacids. It was proved that a suitable selection of the excipients and therefore the modification in the rate in which the drug was released, could play an important role to modify a pharmacokinetic interaction based on a reduction of the solubility of the drug as a function of the pH value of the medium.     

Characterization of Antacid Compounds Containing Both Aluminum and Magnesium. II. Codried Powders

The composition and antacid properties of six samples of codried antacids containing both aluminum and magnesium were determined. Aluminum hydroxide–magnesium carbonate codried gel and aluminum hydroxide–magnesium hydroxide codried gel were non-homogeneous, as the samples contained combinations of hydrotalcite, amorphous aluminum hydroxide, magnesium hydroxide, magnesium hydroxycarbonate, and magnesium carbonate. All samples passed the preliminary antacid test and had high acid neutralizing capacities. However, the rate of acid neutralization varied between samples. In some cases the rate of acid neutralization at a dose of 400 mg was too slow to raise the pH to 3.0 as required by the Rossett–Rice test.     

Assessment of antacid characteristics of drugs containing a combination of aluminium and magnesium salts using the "artificial stomach" model

Antacid characteristics of three drugs containing aluminium and magnesium salts (combination of clay with aluminium and magnesium hydroxides, aluminium and magnesium hydroxide mixture and hydrotalcite) have been studied in a dynamic situation simulated by the "artificial stomach" model, simultaneously taking into account both gastric fluxes, a constant secretory flux and variable emptying fluxes. Therapeutic doses of the drugs were added 1. to 100 ml of 0.1 N HCl, without or with 1% or 5% meat extract, and 2. 100 ml of pooled human gastric juice (96 mmol/l, pH 1.1). In addition, antacid activity of 0.5 g aluminium and magnesium hydroxides, taken alone or in combination, were evaluated when added to 100 ml of 0.1 N HCl. In aqueous HCl solution or in human gastric juice, the three antacid drugs exhibited 1. a neutralising activity characterised by pH-rise and 2. a buffering capacity close to pH 3.8. In addition, hydrotalcite exhibited also buffering capacity at pH 1.2. The antacid-induced capacity, expressed as H+ mmol, to recover initial pH were very similar, indicating that antacid physiochemical properties are similar in HCl solution or in gastric juice. H+ consumption depended upon emptying fluxes. The same antacid characteristics were observed when antacids were mixed with 1% meat extract while 5% meat extract resulted in a modification of antacid characteristics. Therefore the antacid capacities of respective mixtures were of smaller magnitude (50-60%) than the sum of the activities of antacids plus meat extracts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biopharmaceutical properties of liquid and tablet antacids: in vivo studies using the intragastric pH-measurement technique.

Three types of liquid and tablet antacids have been studied in vitro and in vivo: aluminium hydroxide, aluminium hydroxide-magnesium carbonate and hydrotalcite. The effects on gastric pH of antacid suspensions and antacid chewing tablets having identical active ingredients have been studied in 36 volunteers, the sequence of both forms of administration being randomized. Gastric acid secretion was continuously stimulated during the experiment by a pentagastrin infusion. Antacid chewing tablets gave inferior results when compared with the same antacid in liquid. Antacid suspensions are therefore preferred in the treatment of acid-peptic disease.     

The permeability of enteric coatings and the dissolution rates of coated tablets

The effect of an increasing concentration of plasticizer and pigment on the permeability to both water vapour and simulated gastric juice of cellulose acetate phthalate and polyvinyl acetate phthalate has been evaluated. There were significant differences between the permeability coefficients of each polymer, particularly with regard to water vapour. The presence of additives within the film coatings had a greater effect on the properties of cellulose acetate phthalate than those of polyvinyl acetate phthalate. Suitable formulations of each polymer were used to enteric coat 325 mg aspirin tablets, which were subsequently subjected to both the Disintegration Test for Enteric Coated Tablets B.P. and a dissolution procedure to monitor the release of drug in simulated gastric juice and simulated intestinal fluid. Both polymers demonstrated their suitability for producing enteric coatings. However, polyvinyl acetate phthalate yielded a faster release of aspirin in simulated intestinal fluid than did cellulose acetate phthalate.     

Lack of pharmacokinetic interaction between the oral anti-influenza neuraminidase inhibitor prodrug oseltamivir and antacids

AIMS: Oseltamivir is an oral ester prodrug of its active metabolite Ro 64-0802, a potent and selective neuraminidase inhibitor of the influenza virus. The object of this study was to evaluate whether the oral absorption of oseltamivir was reduced in the presence of two main classes of antacid, Maalox(R) suspension (containing magnesium hydroxide and aluminium hydroxide) and Titralac(R) tablets (containing calcium carbonate). METHODS: Twelve healthy volunteers completed a randomized, single dose, three-period crossover study. Each volunteer received in a fasted state, 150 mg oseltamivir alone (Treatment A), 150 mg oseltamivir with a 20 ml Maalox suspension (Treatment B), and 150 mg oseltamivir with four Titralac tablets (Treatment C), with 7-10 days washout in between treatments. Plasma and urine concentrations of oseltamivir and Ro 64-0802 were measured using a validated h.p.l.c./MS/MS assay. Pharmacokinetic parameters were calculated for oseltamivir and Ro 64-0802. Since antacids are locally acting drugs and generally not expected to be absorbed substantially into the systemic system, no plasma or urine concentrations of antacids were measured. RESULTS: Bioequivalence was achieved for the primary pharmacokinetic parameters Cmax and AUC(0, infinity ) of Ro 64-0802 following administration of oseltamivir with either Maalox suspension or Titralac(R) tablets vs administration of oseltamivir alone. The bioavailability (90% confidence intervals) of Ro 64-0802 following administration of oseltamivir together with Maalox suspension vs administration of oseltamivir alone, was 90% (83.6, 96.9%) for C(max) and 94.1% (91.4, 96.9%) for AUC(0, infinity); similarly, for Titralac tablets, the equivalent values were 95.1% (88.3, 102%) for C(max) and 94.7% (91.9, 97.5%) for AUC(0, infinity). CONCLUSIONS: The coadministration of either Maalox suspension or Titralac tablets with oseltamivir has no effect on the pharmacokinetics of either oseltamivir or Ro 64-0802, and conversely, there is no evidence that coadministration with oseltamivir has an effect on the safety and tolerability of either Maalox suspension or Titralac tablets. There was no pharmacokinetic interaction between oseltamivir with either antacid, demonstrating that the oral absorption of oseltamivir was not impaired in the presence of antacids containing magnesium, aluminium or calcium.     

蛇床子素及其β-环糊精包合物在不同溶出介质中的溶出速率研究

目的:考察蛇床子素及其β-环糊精包合物在不同溶出介质中的溶出行为.方法:用紫外分光光度法测定蛇床子素和包合物分别在人工胃液、人工肠液、15%乙醇、30%乙醇、0.2%十二烷基硫酸钠的人工胃液、0.5%十二烷基硫酸钠的人工胃液中的溶出速率.结果:蛇床子素和包合物在人工胃液、人工肠液中溶出太少,不能满足测定条件,在0.5%十二烷基硫酸钠的人工胃液中,溶出很快,不能完全区分二者的溶出度差异,用含0.2%十二烷基硫酸钠的人工胃液作溶出介质,效果较好.结论:介质对蛇床子素及包合物的溶出有很大影响,但在所有溶出介质中包合物的溶出速率均快于蛇床子素,且具有显著性差异(P＜0.05).     

In vitro release--in vivo microbiological and toxicological studies on ketoconazole lipid granules

In some multidrug therapy programs, ketoconazole (KTZ) may be administered with some antacids that could modify its dissolution rate and reduce its absorption, thus leading to therapeutic failures. The primary aim of this study was to evaluate the influence of Compritol HD5 ATO and Compritol 888 ATO on this interaction in comparison with commercial KTZ tablets. The second aim was to prepare lipid granules of KTZ that could be an alternative to the commercial formulation. Therefore, six KTZ sustained-release granules were prepared with different lipid concentrations, because they were found to be more suitable than tablets that are dissolved only in gastric medium. The results confirmed that the dissolution rate of KTZ granules was significantly reduced in the presence of antacids. The ideal formulation was selected as granules including 5% of Compritol lipids in relation to the suitability of the target profile. Therapeutic effects of orally administered, ideal KTZ granule formulations, and commercial tablets were evaluated in vivo by the experimental model of murine vulvo-vaginal candidiasis (VVC) with and without antacids. It was found that formulations were very effective on VVC, and the therapeutic effect decreased significantly in the presence of antacids. Histopathological studies were carried out for vagina, stomach, and liver tissues and hepatoxicity was also examined. The levels of reduced glutathione (GSH) were measured to assess the oxidative stress induced by KTZ and function of the liver. It was observed that orally administered formulations of KTZ were successful in treating candidiasis in mice without irritancy in stomach. However, liver tissues were damaged. The decreased GSH levels indicated toxicity in our study. This study suggested that in vitro release and in vivo microbiological-toxicological properties of KTZ were affected by antacids and drug-excipient interactions. Lipid granules of KTZ prepared with Compritol 888 ATO could be proposed as a new KTZ solid dosage form with optimum dissolution and therapeutic characteristics.     

Biopharmaceutical properties of liquid and tablet antacids: in vivo studies using the intragastric pH-measurement technique

Three types of liquid and tablet antacids have been studied in vitro and in vivo: aluminium hydroxide, aluminium hydroxide-magnesium carbonate and hydrotalcite. The effects on gastric pH of antacid suspensions and antacid chewing tablets having identical active ingredients have been studied in 36 volunteers, the sequence of both forms of administration being randomized. Gastric acid secretion was continuously stimulated during the experiment by a pentagastrin infusion. Antacid chewing tablets gave inferior results when compared with the same antacid in liquid. Antacid suspensions are therefore preferred in the treatment of acid-peptic disease.     

处方中的辅料对瑞舒伐他汀钙片溶出的影响

目的:通过对比溶出曲线,研究处方中的辅料对瑞舒伐他汀钙片溶出的影响。方法:采用粉末直接压片工艺,通过单因素试验,考察处方中乳糖的型号、微晶纤维素的来源、钙盐的种类、交联聚维酮的型号及用量、硬脂酸镁的用量和包衣粉的用量对瑞舒伐他汀钙片溶出的影响。结果:不同的乳糖型号(T80、PW80、315)、微晶纤维素来源(PH102、M102、102)、硬脂酸镁用量(0.5%、1%、2%)、包衣粉用量(2%、3%、4%)对溶出的影响差异较小,钙盐的种类(磷酸钙、无水磷酸氢钙、碳酸钙)、交联聚维酮的型号(XL、XL-10)及用量(3%、5%)对溶出的影响有一定差异。结论:处方中的稳定剂及崩解剂对瑞舒伐他汀钙片的溶出有影响,填充剂、润滑剂及包衣粉对溶出影响较小。