The potentially harmful excipients in prescribed medications in a Neonatal Intensive Care Unit in Kosovo and available safer alternatives.

BACKGROUND: Medicinal products contain excipients that might be associated with toxicity in neonates. The aim of this study was to investigate the administration of medication containing potentially harmful excipients to neonates hospitalized in Kosovo and to identify the possibility of reducing neonatal exposure to these excipients through product substitution. METHODS: Data on all medication administered to hospitalized neonates from 1st of February to 1st of August 2018 along with patients` demographic data were collected from medical records for each neonate. Excipients were identified from the Summaries of Product Characteristics. Three stage criteria for product substitution were: (1) same active pharmaceutical ingredient (API) and route of administration; (2) 1 plus same dosage form; (3) 1 and 2 plus same strength. RESULTS: In total, 100 excipients were found in 2388 prescriptions comprising 67 medications and 60 API administered to 294 (183 preterm and 111 term) hospitalized neonates. The excipients of interest (EOI) were present in 409 (17.1%) prescriptions and were administered to 131 (71.6%) preterm and 52 (46.8%) term neonates through a relatively small number of products (n=27; 32.8%). In relation to prescription frequency, the most common EOI was polysorbate 80, found in 229 (56%) of EOI-containing prescriptions. Substitution with EOIfree products was possible for 14 (63.6%), 12 (54.5%) and 5 (22.7%) products, according to the first-, second- and third-stage criteria, respectively. CONCLUSIONS: We have provided the first detailed description of neonatal exposure to potentially harmful excipients among neonates admitted to a neonatal intensive care unit in Kosovo. Unnecessary exposure could be reduced by using EOI-free products available in the local medicine market. Collaborative initiative is required to build up the evidence on the use of EOI in neonates and raising awareness among health care professionals on use of products without EOI where possible.

Application of Design of Expert software for evaluating the influence of formulation variables on the encapsulation efficacy, drug content and particle size of PEO-PPO-PEO/Poly (DL-lactide-co-caprolactone) nanoparticles as carriers for SN-38.

Background and aims: Hydrophobic substances are mainly encapsulated into polymer nanocarriers in order to improve their solubility, enable their administration, at the same time to empower targeted tissue or cell specific delivery of the drug using the encapsulating vehicle as targeting and controlled release platform. 7-Ethyl-10-hydroxycamptothecin (SN-38) is an active metabolite of Irinotecan, showing 100-fold to 1000-fold higher effect than Irinotecan, but its clinical use is limited because of its extreme hydrophobicity, as it is practically insoluble in most physiologically compatible and pharmaceutically acceptable solvents. Method: In order to fully exploit the potential of the nanoprecipitation as a method for preparation of Poly(DL-lactide-co-caprolactone)-poly(ethylene oxide) - poly(propylene oxide) - poly(ethylene oxide) (P(DL)LCL/PEO-PPO-PEO) nanoparticles and evaluate the influence of the polymer P(DL)LCL, stabilizing agent PEO-PPO-PEO copolymer (Lutrol F127) and the drug concentration (SN-38) upon drug entrapment efficiency, size and drug content, a D-optimal experimental design for response surface using Design Expert Version 9.0.4.1. software investigation was created and statistically analyzed. Results: We have observed that at higher SN-38 concentration during the preparation procedure (nanoprecipitation, solvent diffusion method), and due to its extremely low water solubility, the drug will start to precipitate as unprotected crystals at a faster pace compared to polymer aggregation, leading to extremely low encapsulation efficacy and waste of the active compound. The most desirable combination of factor settings are SN-38 = 0.5 mg, Polymer = 5 mg and F127 = 4%. Conclusion: This investigation utilizes the design of experiment approach and extends the primary understanding of impact of formulation development of P(DL)LCL/PEO-PPO-PEO nanoparticles as carriers for SN-38.