International journal of pharmaceutics
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Alpha-lactose monohydrate is the standard carrier used for dry powder inhalation drug products. The physico-chemical characteristics of this carrier material need to be monitored and specified carefully in order to guarantee functionality of the powder formulation. But also microbiological acceptance criteria need to be considered during development and routine testing. ⋯ Assuming that the typical lactose has an endotoxin content of 10 EU/g and that a patient inhales six times daily 25 mg of lactose and that the total amount of lactose reaches the lung, this translates to an endotoxin exposure of 1.5 EU per day. On the other hand, the proposal for endotoxins in air limits the endotoxin concentration to 50 EU/m3 which corresponds to approximately 3333 EU inhaled endotoxins a day during normal breathing (breathing at rest conditions). The maximum endotoxin exposure by dry powder inhalations is thus two log steps lower than the recommended acceptable daily intake.
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An active pharmaceutical ingredient (API) was found to dissociate from the highly crystalline hydrochloride form to the amorphous free base form, with consequent alterations to tablet properties. Here, a wet granulation manufacturing process has been investigated using in situ Fourier transform (FT)-Raman spectroscopic analyses of granules and tablets prepared with different granulating fluids and under different manufacturing conditions. Dosage form stability under a range of storage stresses was also investigated. ⋯ In contrast, non-aqueous granulating fluids, with no delay in processing and storage of the tablets in either sealed containers or at lower temperature/humidity prevented detectable dissociation. It is concluded that appropriate manufacturing process and storage conditions for the finished product involved minimising exposure to moisture of the API. Analysis of the drug using FT-Raman spectroscopy allowed rapid optimisation of the process whilst offering quantitative molecular information concerning the dissociation of the drug salt to the amorphous free base form.
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Infection has been one of the most common causes of problems and complications after the operation despite the advance in surgical techniques and the availability of newly developed antibiotics. Local antibiotic delivery beads for treatment of various surgical infections had been studied recently especially in osteomyelitis. This current paper used cefazolin sodium and gentamicin sulfate combined with biodegradable polymers (50:50 poly(DL-lactide):co-glycolide) as antibiotic beads for a long-term drug release. ⋯ An elution method combined with a bacterial inhibitory test was employed to characterize the release rate of the antibiotics over a 30-day period. The results suggested that the biodegradable beads released high concentrations of antibiotic (well above the minimum inhibitory concentration) in vitro for the period of time needed to treat bone infection; i.e. 2-4 weeks. This provides advantages as a first line choice of long-term antibiotics for patients with osteomyelitis and various infections such as thoracic, abdominal, and pelvic infections, as well as for the prophylaxis of these infections.
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Comparative Study
Evaluation of childhood exposure to di(2-ethylhexyl) phthalate from perfusion kits during long-term parenteral nutrition.
Leachability of the plasticizer di(2-ethylhexyl) phthalate (DEHP) from administration sets into intravenous parenteral emulsions containing fat was investigated. DEHP is added to polyvinyl chloride (PVC) to impart flexibility. However, DEHP is a lipid-soluble suspected carcinogen that is hepatotoxic and teratogenic in rodents, and has been shown to leach from PVC products containing lipophilic mixtures. ⋯ The same phenomenon was observed after 1 week of storage at 4 degrees C. DEHP extraction by TPN depends on the lipid content of each TPN preparation and the flow rate. These results suggest that children treated with prolonged TPN are regularly exposed to significant amounts of DEHP.
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Comparative Study Clinical Trial
In vitro and in vivo comparison of two diclofenac sodium sustained release oral formulations.
The aim of this study was to investigate the effect of formulation on the pharmacokinetics of diclofenac in two sustained release formulations (formulation A and Voltaren SR) after oral delivery. The dissolution of diclofenac from sustained release formulation was pH-dependent. While drug released from both formulations increased with increased pH, the release kinetics of these two formulations was different. ⋯ There was a significant difference in area under the plasma concentration-time curve [AUC(0-24)] and C(max) observed. The formulation with a reduced diffusion exponent with increased kinetic constant results in increased absorption of diclofenac in vivo. This study demonstrated the impact of release mechanism of the formulation on the absorption in vivo.