Ljubljana, Slovenia
Ljubljana, Slovenia

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Bode G.H.,Maastricht University | Pickl K.E.,Joanneum Research | Sanchez-Purra M.,Ramon Llull University | Albaiges B.,Ramon Llull University | And 34 more authors.
PLoS ONE | Year: 2015

Aims: The aim of the current study was to develop a method to detect peptide-linked nanoparticles in blood plasma. Materials & Methods: A convenient enzyme linked immunosorbent assay (ELISA) was developed for the detection of peptides functionalized with biotin and fluorescein groups. As a proof of principle, polymerized pentafluorophenyl methacrylate nanoparticles linked to biotin-carboxyfluorescein labeled peptides were intravenously injected in Wistar rats. Serial blood plasma samples were analyzed by ELISA and by liquid chromatography mass spectrometry (LC/MS) technology. Results: The ELISA based method for the detection of FITC labeled peptides had a detection limit of 1 ng/mL. We were able to accurately measure peptides bound to pentafluorophenyl meth-acrylate nanoparticles in blood plasma of rats, and similar results were obtained by LC/MS. Conclusions: We detected FITC-labeled peptides on pentafluorophenyl methacrylate nanoparticles after injection in vivo. This method can be extended to detect nanoparticles with different chemical compositions. © 2015 Bode et al.


Jaklic M.,Lek Pharmaceuticals | Kocevar K.,Lek Pharmaceuticals | Srcic S.,University of Ljubljana | Dreu R.,University of Ljubljana
Powder Technology | Year: 2015

Vertical chute transport is a common and widespread means of transporting powders and powder blends in the pharmaceutical industry; conversely, it is also a ready source of segregation. All components of powder mixtures (i.e., active pharmaceutical ingredients, as well as excipients) are subjected to particle size-based segregation, and therefore all properties of the final product, which depend on the particle size of its constituents, may be affected (e.g., compressibility, dissolution rate, API content, and content uniformity). Segregation of single-component pharmaceutical powders with continuous size distributions (excipients or model API) based on particle size was experimentally investigated. Single-component pharmaceutical powders were subjected to fall in a laboratory-scale vertical chute with a closed bottom, and powder samples from various powder bed heights were collected and analysed for particle-size distributions. The results show particle size-based segregation in all materials tested, and the segregation extent and pattern are material-specific. Certain segregation effects were explained with the flow patterns of falling powder and powder bulk properties. An interesting finding is that less cohesive materials with better flowability exhibit increased segregation of smaller sized-D(0.1) particles, which has been attributed to the vertical chute system with a closed, airtight bottom. The size limit, below which particles concentrate at the top of the sediment, and above which particles concentrate at the bottom of the sediment, seems to be universal at 0.46 of D(0.9) value for tested materials. © 2015 Elsevier B.V.


Smrdel P.,Lek Pharmaceuticals | Smrdel P.,University of Ljubljana | Cerne M.,Lek Pharmaceuticals | Bogataj M.,University of Ljubljana | And 3 more authors.
Journal of Microencapsulation | Year: 2010

LK-423 is a phthalimido-desmuramyl-dipeptide derivative with immunomodulating activity. In the present study the therapeutic efficacy of a colon-specific drug delivery systemLK-423 microcapsuleswas examined in the 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced ulcerative colitis model in rats. The colon-specific delivery of the drug using microcapsules relies on the combination of pH (outer gastroresistant coating), time (inner retard coating of Eudragit® RS and RL) and enzyme (pectin core) controlled drug release mechanisms. The optimal in vitro dissolution profile for LK-423 delivery to the colon of rats was obtained after coating newly developed LK-423 loaded pectin cores with 20 w/w of retard coating with a Eudragit® RS/RL ratio of 8.5/1.5 and 30 w/w of enteric coating. Orally administered LK-423 microcapsules were therapeutically more beneficial in treating TNBS-induced ulcerative colitis in rats than orally or rectally administered LK-423 in the form of suspension. Clinical activity scores and colon weight to length ratio were insignificantly lower and the macroscopically estimated degree of healing was significantly greater. On the histological level, the administration of LK-423 microcapsules resulted in most physiological regeneration of intestinal mucosa, indicated by regular architecture of all mucosal tissue components, what is probably related to local drug delivery near the site of inflammation achieved using microcapsules. These results demonstrate that LK-23 colon delivery microcapsules enhance the therapeutic efficacy of the drug and therefore appear to be a useful approach for treating various inflammatory diseases in the large intestine. © 2010 Informa UK Ltd All rights reserved.


Patent
Lek Pharmaceuticals | Date: 2010-01-13

The present invention describes in an embodiment a coating composition which contains in a film coating an active pharmaceutical ingredient, which is defined by a low water solubility of about 10 mg/ml or lower as measured in water at 20 C. at about pH 7, or which is defined by presenting a dispersed state when placed in water at 20 C. at about pH 7, and a co-polymer of polyvinyl alcohol with polyethylene glycol. Preferably the active pharmaceutical ingredient has been applied dispersed in an aqueous coating vehicle onto a core which optionally comprises a same or different active pharmaceutical ingredient. The present invention also describes a process for the preparation of a pharmaceutical single unit dosage form, wherein the process comprised the steps of providing a core of the single unit dosage form, optionally providing one or more subcoating layer(s) on the core, subjecting the core to film coating using a composition comprising an aqueous coating vehicle, a co-polymer of polyvinyl alcohol with polyethylene glycol and at least one active pharmaceutical ingredient dispersed in the aqueous coating vehicle, wherein said co-polymer amounts for at least 7.0 wt. %, preferably at least 9.4 wt. % of said composition and the weight ratio of said co-polymer to said active pharmaceutical ingredient is at least 1:1 to 5:1. Other process embodiments are also described. High drug loads, uniformity of drug load, and fast dissolution rates of active pharmaceutical ingredient from film coatings of pharmaceutical single unit dosage forms can be achieved according to the present invention.


PubMed | Lek Pharmaceuticals
Type: Journal Article | Journal: Journal of microencapsulation | Year: 2010

LK-423 is a phthalimido-desmuramyl-dipeptide derivative with immunomodulating activity. In the present study the therapeutic efficacy of a colon-specific drug delivery system–LK-423 microcapsules–was examined in the 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced ulcerative colitis model in rats. The colon-specific delivery of the drug using microcapsules relies on the combination of pH (outer gastroresistant coating), time (inner retard coating of Eudragit® RS and RL) and enzyme (pectin core) controlled drug release mechanisms. The optimal in vitro dissolution profile for LK-423 delivery to the colon of rats was obtained after coating newly developed LK-423 loaded pectin cores with 20% w/w of retard coating with a Eudragit® RS/RL ratio of 8.5/1.5 and 30% w/w of enteric coating. Orally administered LK-423 microcapsules were therapeutically more beneficial in treating TNBS-induced ulcerative colitis in rats than orally or rectally administered LK-423 in the form of suspension. Clinical activity scores and colon weight to length ratio were insignificantly lower and the macroscopically estimated degree of healing was significantly greater. On the histological level, the administration of LK-423 microcapsules resulted in most physiological regeneration of intestinal mucosa, indicated by regular architecture of all mucosal tissue components, what is probably related to local drug delivery near the site of inflammation achieved using microcapsules. These results demonstrate that LK-23 colon delivery microcapsules enhance the therapeutic efficacy of the drug and therefore appear to be a useful approach for treating various inflammatory diseases in the large intestine.

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