Stabilisation and Growth of Metastable Form II of Fluconazole in Amorphous Solid Dispersions.

The crystallisation of metastable drug polymorphs in polymer matrices has been reported as a successful approach to enhance the solubility of poorly water-soluble drug molecules. This can be achieved using different polymers, drug to polymer ratios and formulation techniques enabling the formation of stable nuclei and subsequent growth of new or metastable drug polymorphs. In this work we elucidated the polymorphism behaviour of a model compound fluconazole (FLU) embedded in solid dispersions with amorphous Soluplus® (SOL) obtained using spray drying and fusion methods. The effect of humidity on the stability of FLU in the obtained dispersions was also evaluated. FLU at a drug content below 40 wt. % stayed amorphous in the dispersions prepared using the fusion method and crystallised exclusively into metastable form II at a drug content above 40 wt. % and 70% relative humidity (RH) conditions. In contrast, a mixture of forms I, II and hydrate of FLU was detected in the spray dried formulations after 14 days of storage at 40 °C/40% RH, with preferential growth of thermodynamically stable form I of FLU. This study highlights the importance of preparation techniques and the drug:polymer ratio in the formulation of amorphous solid dispersions and provides further understanding of the complex crystallisation behaviour of amorphous pharmaceuticals encapsulated in the polymer matrixes.

Thermal stability and decompositions kinetics under non-isothermal conditions of imatinib mesylate α form.

The thermal decomposition and kinetic parameters of synthetized imatinib mesylate α form α form were determined by thermogravimetry (TGA/DTG) under non-isothermal conditions. The experiments were performed at a 25-940°C temperature range at five different heating rates: 2.5Kmin(-1), 5Kmin(-1), 10Kmin(-1), 15Kmin(-1) and 20Kmin(-1) per minute in a nitrogen atmosphere. Imatinib mesylate α form presents one-step mass loss during the degradation process. The thermal stability of the examined material, the melting temperature (Tonset=220.6°C) and ΔH fusion=-95.74Jg(-1) at a heating rate of 10°Cmin(-1) was established. The values of activation energies have been estimated using Kissinger, Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) methods.

Ophthalmic drug dosage forms: characterisation and research methods.

This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommended in vitro and in vivo studies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patient's compliance.

Occurrence of gastrointestinal side effects associated with early use of commercial diets in ITU patients.

BACKGROUND: The purpose of this retrospective study was to analyse the occurrence of gastrointestinal side effects in enterally fed ITU patients. METHODS: We analysed the records of 195 ITU patients fed enterally, over at least five days, with commercial mixtures administered as 20-h infusions. Gastric retention, the number of defecations, and incidents requiring discontinuation of enteral feeding, were noted during the first 3 days of nutrition. RESULTS: Enteral nutrition was usually started during the first week of treatment (median 4, range: 1-33). In 118 patients receiving parenteral nutrition, the median day of implementing enteral feeding was day 5; some received enteral mixtures much earlier (day 2). The mean infusion rates of enteral mixtures were: 33 mL h-1 on day 1, 58 mL h-1 on day 2, and 68 mL h-1 on day 3. Gastric retention was observed in 49 (25.1%) patients during the first day, in 37 (19.0%) on day 2, and in 25 (12.8%) on day 3. Discontinuation of enteral nutrition was necessary in 6 patients due to: surgery (1), high gastric retention (4), gastrointestinal bleeding (1). A statistically significant correlation was found between the occurrence of gastric retention, infusion rates and CRP, and between the number of defecations and infusion rates. CONCLUSIONS: Enteral feeding with commercial diets is well tolerated when implemented gradually. Intolerance and the need for the discontinuation of enteral feeding were usually associated with a worsening of the patient's general condition and progression of the underlying disease.

Analysis of nutrition mixtures in ITU patients.

BACKGROUND: The aim of this study was to analyse the composition of parenteral nutrition (PN) mixtures used in the ITU. METHODS: Restrospective analysis involved 2124 prescriptions for individual PN bags. They were administered over an 18-month period, to 160 ITU patients with the mean APACHE II score of 26 points (range: 5-61), calculated on admission. The mortality rate was 40%. Nutrition programs were prepared individually following the 2009 ESPEN guidelines. The prescription was modified according to the individual patient's clinical condition. One hundred and sixty prescriptions were analysed on the first day of PN (T1), 139 - on the second day (T2) and 1825 on the third and subsequent days (T3). RESULTS: The mean energy supplies were: 1381 kcal/day (range: 456-2612) on T1, 1467 kcal/day (range: 524-2860) on T2, and 1654 kcal/day (range: 390-2969) on T3. The mean supplies of amino acids, glucose and lipids were as follows: amino acids 68.3 g/day (range:20-120) on T1; 71.6 g/ day (range:27.5-125) on T2; 88.0 g/day (range:11-196) on T3; glucose 210.25 g/day (range: 120- 400) on T1; 218.34 g/day (range: 65-480) on T2; 278.5 g/day (range: 18-520) on T3; lipids 34.9 g/ day (range: 0-100) on T1; 38.7 g/day (range: 0-100) on T2; 52.66 g/day (range: 0-117) on T3. The percentages of non-protein energy from lipids were: 29.25 (0-73) on T1; 31.58 (range: 0-60) on T2; 33.5 (0-60) on T3. The following statistically significant differences were found: T2-T3- (p<0.05). CONCLUSIONS: The compositions of nutrition bags prepared for ITU patients were consistent with the ESPEN guidelines. The composition varied on different days of nutrition. The differences in the supply of nutrition components indirectly confirm the need for individual prescriptions for ITU patients.