Statistical Considerations Concerning Dissimilar Regulatory Requirements for Dissolution Similarity Assessment. The Example of Immediate-Release Dosage Forms.

When performing in vitro dissolution testing, especially in the area of biowaivers, it is necessary to follow regulatory guidelines to minimize the risk of an unsafe or ineffective product being approved. The present study examines model-independent and model-dependent methods of comparing dissolution profiles based on various compared and contrasted international guidelines. Dissolution profiles for immediate release solid oral dosage forms were generated. The test material comprised tablets containing several substances, with at least 85% of the labeled amount dissolved within 15 min, 20-30 min, or 45 min. Dissolution profile similarity can vary with regard to the following criteria: time point selection (including the last time point), coefficient of variation, and statistical method selection. Variation between regulatory guidance and statistical methods can raise methodological questions and result potentially in a different outcome when reporting dissolution profile testing. The harmonization of existing guidelines would address existing problems concerning the interpretation of regulatory recommendations and research findings.

WHAT MOTIVATES POLISH COMMUNITY PHARMACISTS TO PURSUIT OF POSTGRADUATE EDUCATION?.

Due to increasing importance of the advisory role for physicians and patients played by the pharmacist over the last decade, it seems appropriate to evaluate if and why pharmacists are interested in postgraduate medical education. The purpose of the study was to develop and validate an instrument to assess such motives, with special interest to Polish community pharmacists. A self-administered questionnaire was completed by a sample of participants of community pharmacist specialization programs and it was analyzed in relation to participants of other postgraduate courses. They were asked to rank their motives on a Likert-like scale and the underlying dimensions for study motives were identified using exploratory and confirmatory techniques. The reasons for taking specialization for community pharmacists were similar as compared to participants of other postgraduate studies. However, the autotelic factor was not so strong and the crucial reason was that such postgraduate training was required to be promoted in work. Basing on Polish results, we propose the division of motives into three groups - autotelic, instrumental and coincidental. The validated self-administered questionnaire based on this division displayed acceptable construct validity and internal consistency, and therefore can be proposed as an example tool to assess the particular motives and expectations of potential postgraduate students and employees in the pharmaceutical job market. The promotion of postgraduate education among pharmacists can improve the quality of pharmaceutical service.

MOTIVATIONS SURROUNDING THE PURSUIT OF A PHARMACY CAREER - THE CASE OF POLISH STUDENTS.

The objective was to examine the motivation for studying pharmacy. A self-administered questionnaire, developed and validated by the authors, was completed by a sample of 414 Polish pharmaceutical students (Year I - Year 5). The students ranked their motives on a Likert-like scale and their underlying dimensions were identified using exploratory and confirmatory techniques. Several socio-demographic variables and future pharmaceutical career plans were-also identified. The reliability and validity of the proposed questionnaire were confinued. Factor analysis revealed three factors determining the choices of the respondents: coincidental, instrumental and autotelic. Two of the top three reasons for studying pharmacy were autotelic. A relatively small percentage of respondents chose a pharmaceutical education due to coincidence. The motivation for choosing a pharmaceutical career remained relatively stable among students of all the study years. The practice point of our survey can be that, basing on Polish case, we,propose the validated self-administered questionnaire that displays acceptable construct validity and internal consistency, and can serve as an example tool to assess the particular motives and expectations of potential students and employees in the pharmaceutical area.

Errors in reporting on dissolution research: methodological and statistical implications.

OBJECTIVE: In vitro dissolution testing provides useful information at clinical and preclinical stages of the drug development process. METHODS: The study includes pharmaceutical papers on dissolution research published in Polish journals between 2010 and 2015. They were analyzed with regard to information provided by authors about chosen methods, performed validation, statistical reporting or assumptions used to properly compare release profiles considering the present guideline documents addressed to dissolution methodology and its validation. RESULTS: Of all the papers included in the study, 23.86% presented at least one set of validation parameters, 63.64% gave the results of the weight uniformity test, 55.68% content determination, 97.73% dissolution testing conditions, and 50% discussed a comparison of release profiles. The assumptions for methods used to compare dissolution profiles were discussed in 6.82% of papers. By means of example analyses, we demonstrate that the outcome can be influenced by the violation of several assumptions or selection of an improper method to compare dissolution profiles. DISCUSSION AND CONCLUSION: A clearer description of the procedures would undoubtedly increase the quality of papers in this area.

The use of biodegradable polymers in design of cellular scaffolds.

The objective of this work was to demonstrate the usage of biodegradable polymers, made of calcium alginate and dibutyrylchitin, in the design of cellular scaffolds having broad application in reconstructive therapy (dentistry, orthopedics). To visualize cells seeded on calcium alginate and dibutyrylchitin polymers DAPI staining of fibroblasts nuclei was used. The cytotoxicity of the materials and microscopic evaluation of the viability of seeded cells was tested with a PKH 67 fluorescent dye. To assess the cellular toxicity the proliferation of fibroblasts adjacent to the tested polymers was examined. The vitability of cells seeded on polymers was also evaluated by measuring the fluorescence intensity of calcein which binds only to live cells. The conducted experiments (DAPI and PKH 67 staining) show that the tested materials have a positive influence on cell adhesion crucial for wound healing - fibroblasts. The self-made dibutyrylchitin dressing do not cause the reduction of viability of cells seeded on them. The in vitro study illustrated the interactions between the tested materials, constructed of calcium alginate or dibutyrylchitin and mouse fibroblasts and proved their usefulness in the design of cellular scaffolds. Examined polymers turned out to be of great interest and promise for cellular scaffolds design.

Effects of 4-week administration of simvastatin in different doses on heart rate and blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats.

INTRODUCTION: Statins and ß1-adrenergic antagonists are well established in cardiovascular events therapy and prevention. The previous study showed that statins might impact on ß-adrenergic signalling and blood pressure in a dose-dependent manner. The aim of the study was to evaluate the impact of 4-week administration of simvastatin given at different doses on the heart rate and blood pressure after injection of metoprolol in rats. MATERIAL AND METHODS: The experiments were performed in normocholesterolaemic and normotensive Wistar rats. Rats received simvastatin in doses of 1, 10 and 20 mg/kg body weight (bw) for 4 weeks. The control group received 0.2% methylcellulose. For the further estimation of the heart rate and blood pressure, metoprolol at 5 mg/kg bw or 0.9% NaCl was injected intraperitoneally. RESULTS: Simvastatin at doses of 1, 10 and 20 mg/kg bw did not influence the heart rate or blood pressure as compared to the control group. Metoprolol injection statistically significantly decreased the heart rate (439.29±14.03 min(-1) vs. 374.41±13.32 min(-1); p<0.05). In rats receiving simvastatin during the 4-week period after metoprolol injection, heart rate and blood pressure (mean, systolic, diastolic) were similar as compared to the group receiving metoprolol alone. CONCLUSIONS: Simvastatin administration during a 4-week period in different doses did not influence the heart rate or blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats.

Stability studies of expired tablets of metoprolol tartrate and propranolol hydrochloride. Part 1. Content determination.

In recent years the growing interest in drug stability problem has been observed. The stability of pharmaceutical products seems to play an important role from the economical point of view. However, there are not many studies that reported about the stability of drugs past their expiration dates. The objective of the current study was to determine tablet content of expired tablets and tablets with expiry date has not been exceeded. The analyzed tablets contained metoprolol tartrate (50 mg) and propranolol hydrochloride (10 mg), respectively. Content determination was performed using HPLC method with UV detection. The proposed method was validated with regard to linearity, sensitivity, intermediate accuracy and precision. No discrepancies between the results of determination and the declared values range for all the analyzed tablets were observed. The results of performed study might suggest that storage of analyzed batches of tablets over time period exceeding the expiry date given by the manufacturer did not influence their contents.

Stability studies of expired tablets of metoprolol tartrate and propranolol hydrochloride. Part 2. Dissolution study.

The objective of the current study was to determine tablet content and perform dissolution test of expired tablets and tablets which expiry date has not exceeded. The analyzed tablets contained metoprolol tartrate (50 mg) and propranolol hydrochloride (10 mg), respectively. Content determination was performed using spectrophotometric method with UV detection; the percent of dissolved substance from tablets during dissolution test was performed using spectrophotometric method, as well. The proposed methods were validated with regard to linearity, sensitivity, and intermediate accuracy and precision. No discrepancies between the results of determination and the declared values range for all the analyzed tablets were observed. The results of performed study might suggest that the storage of analyzed batches of tablets over time period exceeding the expiry date given by the manufacturer did not influence their contents.