Background: Tablet splitting is commonly used in clinical practice as a way to attain a desired drug dose and/or reduce its side effects, particularly among paediatricians and psychiatrists. However, uneven tablet scoring can lead to significant fluctuations of the administered doses, where subpotency or superpotency of drugs might harm the patients. The aim of this study was to evaluate the influence of tablet splitting on dose uniformity of diazepam by the utilisation of Ph. Eur. 9.0 and FDA recommendations. Methods: Mass variation of whole and half-tablets in parallel with the determination of their content uniformity were performed according to the pharmacopoeial methods. The weight loss after tablet splitting was assessed by employing FDA guidelines. It was also investigated if tablet splitting influenced the in vitro dissolution properties of diazepam tablets. Results: Diazepam whole tablets fulfilled the pharmacopoeial requirements in regard to all the investigated properties. The weight uniformity of scored diazepam tablets ranged from 63.80% to 122.55% label claim. The losses of mass after splitting diazepam tablets were 5.71%. Despite the average content of diazepam in half-tablets was found to be 104.24% label claim, the requirements of Ph. Eur. were not fulfilled. Diazepam content in half-tablets ranged from 0.76 mg to 1.21 mg, thus, patients might receive doses that vary by as much as 45%. However, after weight adjustment, diazepam content in each of the tested half-tablets was in the range of 85-115% of the average drug content meeting the Ph. Eur. criteria. Dissolution profiles of whole and half-tablets were found to be similar, following the Hixson-Crowell kinetic model. Conclusion: According to the results, splitting of diazepam tablets greatly influenced the drug content in the obtained parts, ie the dose accuracy was fully dependent of the ability to score the tablet into exactly equal halves.

Solubility and permeability are recognized as key parameters governing drug intestinal absorption and represent the basis for biopharmaceutics drug classification. The Biopharmaceutics Classification System (BCS) is widely accepted and adopted by regulatory agencies. However, currently established low/high permeability and solubility boundaries are the subject of the ongoing scientific discussion. The aim of the present study was to apply data mining analysis on the selected drugs data set in order to develop a human permeability predictive model based on selected molecular descriptors, and to perform data clustering and classification to identify drug subclasses with respect to dose/solubility ratio (D/S) and effective permeability (Peff). The Peff values predicted for 30 model drugs for which experimental human permeability data are not available were in good agreement with the reported fraction of drug absorbed. The results of clustering and classification analysis indicate the predominant influence of Peff over D/S. Two Peff cut‐off values (1 × 10−4 and 2.7 × 10−4 cm/s) have been identified indicating the existence of an intermediate group of drugs with moderate permeability. Advanced computational analysis employed in the present study enabled the recognition of complex relationships and patterns within physicochemical and biopharmaceutical properties associated with drug bioperformance.

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The aim of this study was to compare the dissolution properties of ibuprofen solid oral dosage forms commercially available in Bosnia and Herzegovina and to estimate the influence of dissolution medium composition on the drug release. Eight products (A-H) were subjected to in vitro dissolution test using experimental conditions described in USP42-NF37. Dissolution properties of one selected product were examined in the presence of alcohol (22.2% v/v) and fruit juice (22.2% v/v). Products marked B-H complied with the pharmacopeial criteria. Dissolution profile of product B was similar with dissolution profiles of products D, E, F and G and similarity was also found between products A-D, C-G, D-G and E-F. Drug release from most of the examined preparations fitted best to the Weibull kinetic model. In the presence of alcohol in the medium, higher amount of ibuprofen was dissolved. Contrary, ibuprofen dissolved in the presence of fruit juice was significantly lower. Differences in the dissolution profiles of investigated preparations suggest that their interchangeability should be additionally considered and demonstrated with in vivo bioequivalence studies. Presence of different substances in the medium can affect dissolution properties of ibuprofen, emphasizing the importance of the patient's compliance.

Development of a standard dosimetric facility with protection against external radiation background for the metrological support of highly sensitive radiation monitoring devices in accordance with the requirements of international standards .