Mathematical methods for quantification and comparison of dissolution testing data

In recent years, drug release/dissolution from solid dosage forms has been the subject of intense and profitable scientific developments. Whenever a new solid dosage form is developed or produced, it is necessary to ensure that drug dissolutionoccurs in an appropriate manner. The pharmaceutical industry and the registration authorities do focus, nowadays, on drug dissolution studies. The quantitative analysis of the values obtained in dissolution/release tests is easier when mathematicalformulas that express the dissolution results as a function of some of the dosage forms characteristics are used. This work discusses the analysis of data obtained for dissolution profiles under different media pH conditions using mathematical methodsof analysis described by Moore and Flanner. These authors have described difference factor (f1) and similarity factor (f2), which can be used to characterise drug dissolution/release profiles. In this work we have used these formulas for evaluation of dissolution profiles of the conventional tablets in different pH of dissolution medium (range of physiological variations)

Eliminacija paracetamola urinom kod pušača

The aim of this study was to evaluate the influence of smoking on the urine paracetamol elimination. Fourteen healthy female volunteers took part in this controlled study. Seven (23+/-3 years; 50 +/- 2 kg; x+/-SD) were non-smokers and seven (26 +/- 9 years; 58 +/- 8 kg) were smokers (15 cigarettes per day). After administration of 500 mg of paracetamol, urine sampling was performed at specific times (before drug administration and 1, 2, 3, 4, 6, 9, 12, 16 and 24 hours after). The bioanalytical method used for determination of hydrolyzed paracetamol conjugates in urine samples was UV-spectrometry. The obtained pharmacokinetic parameters of paracetamol, first-order elimination rate constant (â) and elimination half-life (t1/2â), were statistically compared between non-smokers and smokers. There were no significant differences in both elimination parameters (â 0.311 1/h; t1/2â 2.23 h non-smokers vs. â 0.346 1/h; t1/2â 2.19 h smokers) between the groups. However, the differences obtained in inter-individual variability in pharmacokinetic parameters (â SD 0.013 , KV 13.4 % ; t1/2â SD 0.227, KV 4.57% nonsmokers vs. â SD 0.108 , KV 90 % ; t1/2â SD 0.684 , KV 14 % smokers) indicate relatively low predictability of paracetamol elimination in smokers. That requires higher attention in dosing this drug in smokers, especially if some other factors also influence.U radu je ispitivan uticaj sastojaka duvanskog dima na brzinu eliminacije paracetamola urinom. U kontrolisanom ispitivanju je učestvovalo 14 zdravih dobrovoljaca ženskog pola. Sedam su bili nepušači (23±8 godine; 50±2 kg: X±SD), a sedam (26±9 godina; 58±8 kg; X±SD) pušači (15 cigareta dnevno). Određivan je „ukupan” paracetamol u urinu UV- spektrometrijskom metodom, posle hidrolize konjugata paracetamola i oksidacije dobijenog proizvoda, u prisustvu hipobromita, do obojenog jedinjenja - derivata indofenola. Farmakokinetičkom analizom izmerenih koncentracija u urinu izračunati su farmakokinetički parametri: konstanta brzine eliminacije (â) i poluvreme eliminacije paracetamola (t1/2â). Mada vrednosti ovih parametara kod pušača ukazuju na bržu eliminaciju paracetamola, statističkim poređenjem farmakokinetičkih parametara eliminacije kod pušača (â=0,346 1/h i t1/2â=2,19 h) i nepušača (â=0,311 1/h, t1/2â=2,23 h), nije dobijena značajna razlika ( P lt 0,05). Veće vrednosti SD=0,108 i KV=90 % za â i SD=0,684 i KV= 14, 25 % za t1/2â u grupi pušača, u poređenju sa istim parametrima u grupi nepušača (SD=0,013 i KV=13,4 % za â i SD=0,227 i KV=4,57 % za t1/2â), pokazuju veću inter-individualnu varijabilnost farmakokinetičkih parametara eliminacije paracetamola kod pušača. Posledica je relativno niska predvidivost farmakokinetike paracetamola kod pušača, pa je kod njih potrebna veća pažnja u doziranju leka, naročito ako postoji i uticaj drugih faktora farmakokinetičke varijabilnosti

With food to health : proceedings of the 9th International scientific and professional conference

Proceedings contains 7 original scientific papers, 8 professional papers and 1 review paper which were presented at "9th International Scientific and Professional Conference WITH FOOD TO HEALTH", organised in following sections: Nutrition, Dietetics and diet therapy, Food safety, Food analysis, Production of safe food and food with added nutritional value

In Vitro Modeling of the Influence of FVIII Activity and Heparin Induced Prolongation of APTT

Anticoagulant therapy is most commonly assessed by measuring the effect of the drug on global clotting assay, such as APTT. It is known that response of the APTT to hepa-rin may be decreased in patients with high levels of factor VIII. In this work, we have attempted to determine in vitro conditions of experiment for obtaining relationship between different concentrations of heparin and values of APTT, and to investigate influence of factor VIII on correlation between concentrations of heparin and APTT. Measurement of the effect of heparin, added in vitro in normal coagulation control plasma (NCCP) showed that heparin in concentrations from 0,1 to 1,0 IU/mL prolonged APTT from 0,73 s to 99,26 s. Linearity of the relation of natural logaritm of APTT and concentration of added heparin in plasma for concentrations from 0,5 to 1,0 IU/mL (r = 0,995), and other characteristics of the validated method (RSD = 1,17%), made possible investigation of the influence of factor VIII addition in the solution. The addition of the Factor VIII concentrate, markedly influenced these APTT results. Increased factor VIII activity shortened the APTT, having more pronounced effect in the presence of the large amounts of heparin. Increased factor VIII was associated with downward shift in the concentration -logAPTT response curve (y = 24,644 x + 30,17 vs. y = 10,864 x + 27,256). This finding suggests the possibility for modeling of ex vivo establishment of correlation between plasma activity of FVIII and needed doses of heparin for appropriate management of heparin therap

Formulation ingredients for toothpastes and mouthwashes

In order to achieve the multi-claim products required for the dental care category, it is necessary for the formulator to use a variety of different ingredients. This places a number of demands on the development process. Innovations in the areas of pharmaceutical technology have contributed to the formulation of the products having superior efficacy as well as other attributes that may contribute to clinical response and patient acceptability. Improved clinical efficacy and tolerability, along with conditioning signals, should encourage patient compliance with oral hygiene further complementing professional efforts directed at disease prevention. The most effective way of preventing the development of dental disease is in controlling the production of dental plaque. It is formed by microbial action. The removal of plaque from the teeth and related areas is essential for the maintenance of a healthy mouth. In this paper we have presented the main components of toothpastes and mouthwashes. For the active ingredients, their supposed effect as therapeutic agents is also explained

Formulation ingredients for toothpastes and mouthwashes

In order to achieve the multi-claim products required for the dental care category, it is necessary for the formulator to use a variety of different ingredients. This places a number of demands on the development process. Innovations in the areas of pharmaceutical technology have contributed to the formulation of the products having superior efficacy as well as other attributes that may contribute to clinical response and patient acceptability. Improved clinical efficacy and tolerability, along with conditioning signals, should encourage patient compliance with oral hygiene further complementing professional efforts directed at disease prevention. The most effective way of preventing the development of dental disease is in controlling the production of dental plaque. It is formed by microbial action. The removal of plaque from the teeth and related areas is essential for the maintenance of a healthy mouth. In this paper we have presented the main components of toothpastes and mouthwashes. For the active ingredients, their supposed effect as therapeutic agents is also explained

In Vitro Modeling of the Influence of FVIII Activity and Heparin Induced Prolongation of APTT

Anticoagulant therapy is most commonly assessed by measuring the effect of the drug on global clotting assay, such as APTT. It is known that response of the APTT to hepa-rin may be decreased in patients with high levels of factor VIII. In this work, we have attempted to determine in vitro conditions of experiment for obtaining relationship between different concentrations of heparin and values of APTT, and to investigate influence of factor VIII on correlation between concentrations of heparin and APTT. Measurement of the effect of heparin, added in vitro in normal coagulation control plasma (NCCP) showed that heparin in concentrations from 0,1 to 1,0 IU/mL prolonged APTT from 0,73 s to 99,26 s. Linearity of the relation of natural logaritm of APTT and concentration of added heparin in plasma for concentrations from 0,5 to 1,0 IU/mL (r = 0,995), and other characteristics of the validated method (RSD = 1,17%), made possible investigation of the influence of factor VIII addition in the solution. The addition of the Factor VIII concentrate, markedly influenced these APTT results. Increased factor VIII activity shortened the APTT, having more pronounced effect in the presence of the large amounts of heparin. Increased factor VIII was associated with downward shift in the concentration -logAPTT response curve (y = 24,644 x + 30,17 vs. y = 10,864 x + 27,256). This finding suggests the possibility for modeling of ex vivo establishment of correlation between plasma activity of FVIII and needed doses of heparin for appropriate management of heparin therap

The posology and trough concentrations of digoxin in adult and elderly patients

Being a narrow therapeutic index drug, digoxin may cause harm if dosed without regular measurements of serum levels. Due to various limitations in its dosing, different challenges still exist in clinical practice. This study aimed to assess digoxin though concentrations after different regimens in adult and elderly patients, and to identify predictor variables for the ratio of given dose and digoxin trough level. This was prospective open-label study. Digoxin was administered per os as 0.125. or 0.25 mg during different continuous and interrupted dosage regimens. Study protocol allowed an additional therapy according to contemporary guidelines. Digoxin concentrations were determined using Abbott AxSYM Digoxin II assay in trough samples (1-3 per patient) after 3-4 weeks stable regimen. In total, 191 concentrations (104 patients) were analyzed. Digoxin weekly dose was in range 0.375-1.75 mg. On average, we observed slightly lower digoxin levels in 1-117 patients. Results showed that in patients receiving digoxin with interrupted dosage regimen post pause digoxin level was statistically significantly lower than pre-pause (p lt 0.05). Based on multiple linear regression, the ratio of given dose and trough concentration was mainly predicted by clearance creatinine, and to lesser extent by patient's ideal body weight. Interrupted dosing schedule shows greater variability in drug levels comparing to continuous dosing, and it additionally causes difficulties in reaching and maintaining steady trough levels between doses. Hence, individualization of dosing regimen should he carefully guided based on target levels and not solely on clinical signs and symptoms

The new trends in theophylline therapy

Sustained-release theophylline pellets formulation for once-daily evening administration significantly improved patients compliance and adjusted serum levels profile of the drug. The patients conversion from i.v. to p.o. therapy is one of the most critical steps in the treatment of asthma according to its chronopathophysiological character. In our study we have examined safety and efficiency of this conversion in twelve hospitalised asthmatic patients who were given the new sustained-release theophylline pellets formulation for once-daily evening administration. The lung function parameters (FEV1, VC, RV, and Rt) and serum theophylline concentrations were monitored. So, the values obtained for the last day of i.v. therapy and the fifth day of p.o. therapy were compared. We found that 75% of the patients had no change or improved lung function on the conversion. Our results indicate that this conversion from i.v. to p.o. theophylline therapy is safe and could be efficacious. Also, the maximum theophylline serum levels could safely be predicted by measuring only one serum concentration in p.o. therapy with sustained-release theophylline pellets formulation for once-daily evening administration