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The low water solubility of an active pharmaceutical ingredient (aripiprazole) is one of the most critical challenges in pharmaceutical research and development. This antipsychotic drug has an inadequate therapeutic impact because of its minimal and idiosyncratic oral bioavailability to treat schizophrenia. The main objective of this study was to improve the solubility and stability of the antipsychotic drug aripiprazole (ARP) via forming binary as well as ternary inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD) and L-Arginine (LA) as solubility enhancers. Physical mixing and lyophilization were used in different molar ratios. The developed formulations were analyzed by saturation solubility analysis, and dissolution studies were performed using the pedal method. The formulations were characterized by FTIR, XRD, DSC, SEM, and TGA. The results showcased that the addition of HPβCD and LA inclusion complexes enhanced the stability, in contrast to the binary formulations and ternary formulations prepared by physical mixing and solvent evaporation. Ternary formulation HLY47 improved dissolution rates by six times in simulated gastric fluid (SGF). However, the effect of LA on the solubility enhancement was concentration-dependent and showed optimal enhancement at the ratio of 1:1:0.27. FTIR spectra showed the bond shifting, which confirmed the formation of new complexes. The surface morphology of complexes in SEM studies showed the rough surface of lyophilization and solvent evaporation products, while physical mixing revealed a comparatively crystalline surface. The exothermic peaks in DSC diffractograms showed diminished peaks previously observed in the diffractogram of pure drug and LA. Lyophilized ternary complexes displayed significantly enhanced thermal stability, as observed from the thermograms of TGA. In conclusion, it was observed that the preparation method and a specific drug-to-polymer and amino acid ratio are critical for achieving high drug solubility and stability. These complexes seem to be promising candidates for novel drug delivery systems development.

BackgroundUniversity Medical Center in Lubbock, TX is one of few medical centers using Becton Dickinson (BD) Kiestra Total Laboratory Automation (TLA) system since May 2015. The impact on organism-specific turn around time (TAT) in urinary specimens after implementation of TLA was evaluated.MethodsAfter approval from the Quality Improvement Review Board, a retrospective analysis of microbiological data from urinary specimens in BD research database was performed. Before vs. after implementation (2013 vs. 2016) TAT was compared. Ten clinically relevant organisms were analyzed. Statistical analysis was performed with SAS software version 9.2. Data were analyzed using Chi-squared test. A P-value of < 0.05 was considered statistically significant.ResultsOverall, 2282 specimens from 2013 and 2306 specimens from 2016 were analyzed. Compared with before vs. after implementation of TLA, an overall improvement in TAT was observed (expressed as mean hours for each organism): Enterococcus faecalis (55.2 vs. 38.8), Enterococcus faecium (68.4 vs. 43.8), Escherichia coli (44.2 vs. 41.0), Klebsiella pneumoniae (45.0 vs. 44.0), Proteus mirabilis (44.8 vs. 38.6), Pseudomonas aeruginosa (58.9 vs. 37.7), Staphylococcus aureus (49.2 vs. 36.0), Streptococcus agalactiae (49.2 vs. 31.4), Streptococcus pneumoniae (51.7 vs. 61.8), Streptococcus pyogenes (62.6 vs. 26.6). It was also observed that improvement in TAT was more pronounced for Gram-positive organisms than Gram-negative organisms. P-value was < 0.01 for all organisms except Streptococcus pneumoniae (0.7985) and Streptococcus pyogenes (0.2562). The number of specimens with these two organisms was too small to be considered significant.ConclusionAutomation of microbiology laboratory leads to significant TAT improvement in urinary specimens, making early data availability to clinicians. This improves efficiency as well as supporting earlier antibiotic switch, antimicrobial stewardship and optimal patient care in treating urinary tract infections.Disclosures All authors: No reported disclosures.