Background: Nifuroxazide is well known and often used anti-diarrhoeal medicine which has been pushed back from routine practice in recent years and often replaced with probiotics. Even probiotics are accepted and placed in some therapeutic guidelines for diarrhoea treatment, there are no enough evidence for its effectiveness and no comparative efficacy data with nifuroxazide in treatment of acute diarrhea. Patients and Methods: In open, prospective observational study, the efficacy and safety of nifuroxazide were compared with a probiotic containing lactic acid bacteria in the treatment of acute diarrhoea. A total number of 169 adult patients were included in this study, who administered nifuroxazide in the dose of 200 mg/4 times a day, while they took preparation containing lactic acid bacteria (1,2 x 107 live lyophilised lactic-acid bacteria) three times a day for three days. Results: Mean time to last unformed stool (TLUS) in a group which was treated with nifuroxazide was two days, while it took five days for the stool normalisation in the group using probiotic (p=0.0001). Conclusions: Orally administered nifuroxazide has demonstrated better efficiency as compared to probiotic in treating acute diarrhoea, and both medicines have shown the same safety and tolerance in this study.

Chlorphenamine maleate is a first-generation alkylamine antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. Because of that it is frequently used in multicomponents pharmaceutical formulations against the cold. Since the method for determination chlorphenamine related substances in pharmaceutical products is not described in current pharmacopoeias, the aim of this work was to develop and validate a precise, accurate and robust method. HPLC method for determination related substances of chlorphenamine maleate has several problems, how to separate all active ingridients and their impurity in this formulation. Also, problem was to separate placebo in syrup because of presented flavor. Separation was achieved on a reversedphase C-18 column (5 μm, 25 cm x 0.46 cm, kept at 30°C), using a mixture of potassium dihydrogen phosphate and octane sulphonate sodium salt in water and acetonitrile as mobile phase, at flow rate 1.0 ml/min and UV detection at 214 nm. The method was validated following ICH guidelines and validation parameters showed that it could be used as stability indicating method for determination of related substances of chlorphenamine maleate in multicomponents syrups and tablets.

When the fast absorption of diazepam is needed in order to suppress febrile convulsions and epileptic seizures, the most suitable is intravenous application diazepam. To avoid inappropriate self administration of such diazepam dosage form, orodispersible tablets of diazepam would be the dosage form of choice. Poor solubility of diazepam in water is directly related to its dissolution rate after release from a solid dosage form. Inadequate dissolution rate of diazepam can be the limiting factor for its absorption rate. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin was carried out to increase the solubility of diazepam at pH 6.8. Determination of the intrinsic dissolution rate of diazepam as well as complexated diazepam was carried out to predict the absorption rate of diazepam at given pH value. The solubility of micronized diazepam (particle size 5.4 µm) at pH 6.8, was 0.043 mg mL-1, while the solubility of non-micronized diazepam (particle size 414.8 µm) at the same pH was 0.036 mg mL-1. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin resulted in increased solubility of diazepam. One mole of 2-hydroxypropyl-β-cyclodextrin increased the solubility of micronized diazepam 6.82 fold, while two moles of 2-hydroxypropyl-β-cyclodextrin increased the solubility of diazepam 12.55 fold. Given that the values of intrinsic dissolution rates (IDR) of micronized diazepam, non-micronized diazepam and inclusion complex D: 2-HP-β-CD 1:1 were less than 0.1 mg min-1 cm-2, the absorption of diazepam dissolution would be the rate limiting step to absorption, while the inclusion complex D: 2-HP-β-CD 1:2 where an IDR value was greater than 0.1 mg min-1 cm-2 at pH 6.8, suggested that its dissolution might be the rate-limiting step to absorption. Hydroxypropyl-β-cyclodextrin increased the solubility of diazepam at pH 6.8, thus increasing the dissolution rate and causing faster absorption of diazepam at pH 6.8.

Metoprolol is a cardioselective β-blocker that is classified as a class I substance according to the Biopharmaceutics Classification Scheme BCS, meaning that it is highly soluble and highly permeable. [...]

Diazepam is one of most frequently prescribed benzodiazepines. It is classified as a class I substance according to the Biopharmaceutics Classification Scheme (BCS). Diazepam tablets were prepared using different API rawmaterials. Before the formulation, we measured particle size distribution on Malvern Instruments Ltd Mastersizer 2000. The tablets were prepared by employing conventional wet granulation. The formulations were evaluated for hardness, friability, content uniformity, in vitro disintegration time (DT), release profiles. The dissolution profile testing is performed on the two formulations with different particles size distribution. Test parameters were: medium 0.1 mol / l hydrochloric acid, 900 ml, temperature 37°C ± 0.5°C, Mixing Speed 100 rpm, Number of tested tablets 12, Testing Cycle 10, 15, 20, 25 and 30 min. Instrument: Varian Van Kel VK7025, Varian Cary 50. We used the spectrophotometric method with absorbance measuring on 242 nm for quantification. Results for particle size distribution for first Diazepam API particle distribution were d (0.10): 88.743 μm; d (0.50): 305.231 μm; d (0.90): 655.911 μm, and for the second raw-material of API was d (0.10):1.998 μm; d (0.50): 4.419 μm; d (0.90): 8.845 μm. The results of diazepam dissolution for two formulations and f2 value with reference drug are presented in Table 1:

The aim of this trial was to examine the effects of antihypertensive fixed combination of lisinopril plus hydrochlorothiazide (Lopril H, Bosnalijek dd, Bosnia and Herzegovina) on regression of left ventricular hypertrophy in patients with essential arterial hypertension. We included 297 patients in our trial, aged 54.65+/-9.6 years, with treated or untreated hypertension and with high risk of cardiac events, in an opened trial of therapy based on lisinopril plus hydrochlorothiazide. Patients from five European countries were followed up for a period of 12 weeks. Duration of treatment was 12 weeks. We adjusted daily doses of lisinopril plus hydrochlorothiazide after every clinical examination and recorded adverse effects of drugs. In the beginning and after 12 weeks of treatment, 277 patients (93.2%) underwent 2-dimensional echocardiography and there were 186 patients evaluated for efficacy of treatment on left ventricular hypertrophy (LVH). We recorded a regression of index mass LVH (168.56 vs 161.51 g/m2, P<0.0001), and regression was something more in women vs men. We recorded average reduction of left ventricular mass index for patients with LVH (N=186) by 7.05 g/m2 (4.18%) in all patients, by 6.73 g/m2 (3.93%) in men and 7.27 g/m2 (4,37%) in women. The proportion of patients who attained a regression of left ventricular mass tended to be greater in men (54.55% vs 53.21%). This research has proved regression of LVH in more than 53% patients after using fixed combination of lisinopril plus hydrochlorothiazide.

The aim of this trial was to examine the efficacy and safety of antihypertensive fixed combination lisinopril plus hydrochlorothiazide (Lopril H, Bosnalijek dd) in the treatment of essential arterial hypertension. In our trial we included 297 patients, aged 54.65+/-9.6 years, with treated or untreated hypertension and with high risk of cardiac events, in an opened trial of therapy based on lisinopril plus hydrochlorothiazide. Upon the examination by physicians, patients were divided into three groups in accordance with European Society of Cardiology guidelines for the management of arterial hypertension. Patients from five European countries were followed up for a period of 12 weeks. Duration of treatment was 12 weeks. We adjusted daily doses of lisinopril plus hydrochlorothiazide after every clinical examination and recorded adverse effects of drugs. After 12 weeks of treatment, 288 patients (96%) were evaluated for efficacy, tolerability and safety. In almost 81.5% patients with mild, moderate and severe hypertension, we recorded a reduction in blood pressure to approximately normal values SBP and DBP (140/90 mmHg). Drug-related side-effects occurred in 11 patients (3.66%). The most commonly reported adverse effects associated with lisinopril plus hydrochlorothiazide were cough (5) and dry mouth (5). This research has proved good efficacy of fixed combination lisinopril plus hydrochlorothiazide with more than 97% patients. Based on subjective estimation by patients: this drug improved quality of life in all cases.

The amount of bioavailable active substance is essential in demonstrating therapeutic drug efficacy. In vitro technique regarding the comparison of released quantity of active substance from drug can be a relevant anticipation test for in vivo drug characteristics. Comparison is usually conducted between test generic drug and a referent, innovative product (1). This comparative study shows the release of nitrazepam content from preparations Trazem® tablets 5 mg (Bosnalijek - test product) and Mogadon® tablets 5 mg (ICN Iberica S.A., Barcelona, Spain - referent product). Based on the results obtained from the analysis, similarity factor f2 may be calculated. It is a parameter that, according to FDA guidelines (US Food and Drug Administration), measures similarity of dissolution profiles between two preparations. When two dissolution profiles are identical, f2 = 100. In case when f2 value ranges between 50 and 100, FDA defines that such two dissolution profiles may be considered similar (2).

Endogen phospholipids play a major role in determining the structure and nature of cell membranes. A deficiency of phospholipids in cellular membranes makes it almost impossible for the cell membrane to perform its function as a selective barrier between what passes in and out of the cell. Polyenylphosphatidylcholine chemical structure corresponds to that of endogen phospholipids, but it possesses functional superiority because of its content of unsaturated fatty acids. Polyenylphosphatidylcholine integrates in the cell membrane and organelle systems while becoming their constitutive elements. A healthy cell membrane leads to healthy cells and then healthy tissue and then to healthy organs or body systems and finally, healthy bodies and minds. For a long time, polyenylphosphatidylcholine in combination with vitamins has been used in the treatment of numerous health problems such as liver diseases, dyslipoproteinaemias and different intoxications with consequent liver failure. The main aim of toxicology studies is evaluation of the toxic potential and risks of human exposition to the substance. According to the Organization for Economic Cooperation and Development (OECD) acute oral toxicity refers to those adverse effects occurring following oral administration of a single dose of a substance or multiple doses given within 24 hours. LD50 (median lethal dose), oral, is a statistically derived single dose of a substance that can be expected to cause death in 50 per cent of animals when administered by the oral route. Our acute toxicity study was performed on albino Wistar rats. Animals were randomised in three experimental and one control group, each of 5 males and 5 females. Study was based on the administration of a single oral dose of the test substance (polyenylphosphatidylcholine) to each experimental animal. There were three dose-levels of the test substance: 300, 500 and 1000 mg/kg. Test substance administration day was the first day of the observation period that lasted 14 days. Control animals were given milk vehicle. At the end of the study, no statistically significant differences between experimental and control animals were observed concerning the recorded parameters: body weight, respiratory rate, tremor, faeces and phonation quality, indicating the absence of the test substance acute toxicity.

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