Assessment and Optimization of the Pediatric Parenteral Nutrition Preparation Process in a Hospital Pharmacy.

BACKGROUND: Parenteral nutrition (PN) is associated with risks that could threaten the clinical condition of premature neonates hospitalized in the neonatal intensive care unit. In this work, risk-analysis methodology was implemented to contain the risks associated with the PN production process and improve PN safety. METHODS: The Failure Modes, Effects, and Criticality Analysis was performed by a multidisciplinary team. All potential failure modes of the PN preparation process were recorded, and associated risks were scored based on their severity, occurrence, and detectability, with a risk priority number (RPN). All identified failure scenarios and the respective work stages were ranked in descending order of criticality. Corrective actions were proposed to address critical points, and the safety of the process was reassessed by the same method in a prospective manner. RESULTS: The highest RPN scores were obtained with the PN composition calculation performed manually (RPN: 530) or electronically (RPN: 478), completion of the PN medical order form (RPN: 354), manual compounding of PN admixtures (RPN: 258), and the structure/organization/maintenance of the PN preparation unit (RPN: 133). The quality and safety of PN admixtures could be compromised by many critical factors, such as the increased particle-microbial load in the unit and the inadequate training/experience of the involved health professionals and their incompliance with the given instructions. The implementation of the proposed corrective measures is expected to reduce the risks of the overall PN production process by 67.5%. CONCLUSIONS: Improvement of the PN production process through risk-analysis methodologies enhances safety for premature neonates.

Improvement of Chemotherapy Solutions Production Procedure in a Hospital Central Chemotherapy Preparation Unit: A Systematic Risk Assessment to Prevent Avoidable Harm in Cancer Patients.

OBJECTIVE: This study was designed to reevaluate and improve the quality and safety of the chemotherapy preparation in a Central Chemotherapy Preparation Unit of a Public Hospital. METHODS: A failure modes, effects, and criticality analysis (FMECA) was conducted by a multidisciplinary team. All potential failure modes at each stage of the chemotherapy preparation were recorded, and the associated risks were scored for their severity, occurrence, and detectability with a risk priority number (RPN). Corrective actions were suggested, and new RPNs were estimated for the modified process. RESULTS: Failure modes, effects, and criticality analysis and priority matrix construction, revealed that the partial compliance of Unit's premises with international standards (RPNstage: 307), the human errors throughout the compounding (RPNstage: 223)-labeling (RPNstage: 216)-prescribing (RPNstage: 198) steps, and the violation of working protocols by employees (RPNstage: 215), were the most important risks for which either urgent or immediate corrective actions had to be taken. Modifying the procedure through the proposed corrective actions is expected to lead to a significant (71.3%) risk containment, with a total RPNpreparation process reduction from 2102 to 604. CONCLUSIONS: Failure modes, effects, and criticality analysis and priority matrix development identified and prioritized effectively the risks associated with chemotherapy preparation allowing for the improvement of health services to cancer patients.

Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content.

Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity). Clear and systematic understanding of nanoparticle properties' effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol) (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area) and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to calculate (predict) biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for description of PLGA-mPEG nanoparticle biodistribution. Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to experimental data, reflecting properly developed property-biodistribution relationships.

Transcutaneous delivery of a nanoencapsulated antigen: induction of immune responses.

We investigated the influence of antigen entrapment in PLA nanoparticles on the immune responses obtained after transcutaneous immunization. OVA-loaded PLA nanoparticles were prepared using a double emulsion process. Following application onto bare skin of mice in vivo, fluorescence-labeled nanoparticles were detected in the duct of the hair follicles indicating that the nanoparticles can penetrate the skin barrier through the hair follicles. Although the OVA-loaded nanoparticles elicited lower antibody responses than those induced by OVA in aqueous solution they were more efficient in inducing cytokine responses. In vitro re-stimulation of cultured splenocytes with OVA elicited a little higher levels of IFN-gamma (difference statistically insignificant, p>0.05) and significantly higher levels of IL-2 (p<0.001) in mice immunized with OVA-loaded nanoparticles compared to those immunized with OVA in solution. In the presence of CT, the OVA-loaded nanoparticles induced significantly higher IFN-gamma and IL-2 than all other formulations. Transcutaneous administration of OVA encapsulated in the PLA nanoparticles exhibited priming efficacy to a challenging dose of OVA given via different route. These findings indicate the potential of nanoparticles to deliver antigens via the transcutaneous route and prime for antibody and strong cellular responses. The co-administration of an adjuvant such as CT had the added advantage of modulating the immune response, a desirable characteristic within the context of vaccination against intracellular versus extracellular pathogens.