Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity

The incorporation of a drug into mesoporous silica (MPS) is a promising strategy to stabilize its amorphous form. However, the drug within MPS has shown incomplete release, despite a supersaturated solution being generated. This indicates the determination of maximum drug loading in MPS below what is experimentally necessary to maximize the drug doses in the system. Therefore, this study aimed to characterize the drugs with good glass former loaded-mesoporous silica, determine the maximum drug loading, and compare its theoretical value relevance to monolayer covering the mesoporous (MCM) surface, as well as pore-filling capacity (PFC). Solvent evaporation and melt methods were used to load each drug into MPS. In addition, the glass transition of ritonavir (RTV) and cyclosporine A (CYP), as well as the melting peak of indomethacin (IDM) and saccharin (SAC) in mesoporous silica, were not discovered in the modulated differential scanning calorimetry (MDSC) curve, demonstrating that each drug was successfully incorporated into the mesopores. The amorphization of RTV-loaded MPS (RTV/MPS), CYP-loaded MPS (CYP/MPS), and IDM-loaded MPS (IDM/MPS) were confirmed as a halo pattern in powder X-ray diffraction measurements and a single glass transition event in the MDSC curve. Additionally, the good glass formers, nanoconfinement effect of MPS and silica surface interaction contributed to the amorphization of RTV, CYP and IDM within MPS. Meanwhile, the crystallization of SAC was observed in SAC-loaded MPS (SAC/MPS) due to its weak silica surface interaction and high recrystallization tendency. The maximum loading amount of RTV/MPS was experimentally close to the theoretical amount of MCM, showing monomolecular adsorption of RTV on the silica surface. On the other hand, the maximum loading amount of CYP/MPS and IDM/MPS was experimentally lower than the theoretical amount of MCM due to the lack of surface interaction. However, neither CYP or IDM occupied the entire silica surface, even though some drugs were adsorbed on the MPS surface. Moreover, the maximum loading amount of SAC/MPS was experimentally close to the theoretical amount of PFC, suggesting the multilayers of SAC within the MPS. Therefore, this study demonstrates that the characterization of drugs within MPS, such as molecular size and interaction of drug-silica surface, affects the loading efficiency of drugs within MPS that influence its relevance with the theoretical value of drugs.

Using Metabolite Data to Develop Patient Centric Specification for Amide Impurity in Vildagliptin Tablets

Many specified impurities in vildagliptin's finished product have been disclosed in the literature that are above their qualification threshold. We used the impurity B (amide impurity) as a case example to explore whether existing literature can be leveraged to determine the safe level of impurity and thereby develop a patient-centric specification (PCS) for impurities. No-observed-adverse-effect level (NOAEL) was derived from rate metabolism information and converted to human equivalent dose (HED). The HED was estimated as 6.5 mg/day. The high qualification levels are supported by repeat dose toxicity studies performed in rats, mice and dogs. Maximum theoretical amount (MTA) was correlated with the maximum observed amount (MOA) to verify whether the exposure was due to impurity and/or metabolite. MOA/MTA was found ≥1 suggesting that metabolism contributed to the amount excreted in feces and therefore could be used to further justify a higher specification limit than the usual one of ≤0.5%. Quite often the drug metabolism and degradation pathways overlap, resulting in the formation of identical constituents. Therefore, metabolism data can be leveraged for deriving safe levels of degradation impurities and develop PCS for impurities.

Effects of calcium silicate synthesized in situ on Fiber loading and paper properties

The in-situ synthesis of calcium silicate in the fiber can not only meet the requirements for high loading of paper, but also make up and improve the reduction of paper performance caused by filling. In this investigation, the effects of pulp type, beating degree, fiber ratio, reaction time, rotational speed, dosage of lime milk and dispersant on calcium silicate loading and paper properties were investigated. The results showed that when the beating degree was 40 °SR, the ratio of softwood and hardwood pulp was 1:1, the reaction time was 60 min, the rotation speed was 600 r·min−1, the dosage of lime milk was 1.33 times of the theoretical amount, and the dosage of cationic polyacrylamide was 0.3 % (absolutely dry pulp), the ash content of hand-made sheet was 41.2 %, and the loading amount of calcium silicate was 26.3 %. Under this condition, the comprehensive performance of paper was the best.

Flowback Analysis Methodologies and Precipitation Risk During Siderite-Bearing Carbonate Acidizing

Acidizing is the most commonly used method to stimulate carbonate reservoirs. To achieve a better assessment of the operation, a flowback analysis is conducted. Flowback analysis can give insights on the reservoir's response to the recipe. This analysis can be used to improve future treatment operations where some recommendations were deduced. The objective of this paper was to show the flowback analysis methodology following carbonate acidizing treatments with a focus on dissolved elements. X-ray diffraction (XRD), X-ray fluorescence (XRF), environmental scanning electron microscope (ESEM), and inductive coupled plasma (ICP) were used to determine the composition of flowback fluids and the filtered precipitate. Combining the data from different techniques onsite and in laboratory assess the development of a methodology for calculating more accurate amounts of dissolved elements, formation water, and volumes of recovered fluids. This analysis showed acid recipes efficiency of nearly 100% based dissolved calcite. Around 65% of injected fluids were lost into a formation. The iron concentration during the flowback was 1400 ppm, however, cumulative amount of iron in flow back samples was below expected value. Based on the formation's rock analysis, the theoretical amount of iron in the recovered flowback fluid was 1000 kg. The measured amount of iron was 500 kg and the rest could be assumed to be precipitated in a reservoir. This study helps in understanding the flowback fluid analysis and its importance by using a step-by-step analysis procedure for flowback fluid samples from the carbonate acidizing operations. The results of this study help in tracking the elements that potentially help in estimating the lost fluids volumes and percentage of success for a carbonate reservoir acid operation.

Rutin-Loaded Solid Lipid Nanoparticles: Characterization and In Vitro Evaluation

This study was aimed at preparing and characterizing solid lipid nanoparticles loading rutin (RT-SLNs) for the treatment of oxidative stress-induced diseases. Phospholipon 80H® as a solid lipid and Polysorbate 80 as surfactant were used for the SLNs preparation, using the solvent emulsification/diffusion method. We obtained spherical RT-SLNs with low sizes, ranging from 40 to 60 nm (hydrodynamic radius) for the SLNs prepared starting from 2% and 5% (w/w) theoretical amount. All prepared formulations showed negative zeta-potential values. RT was efficiently encapsulated within SLNs, obtaining high encapsulation efficiency and drug content percentages, particularly for SLNs prepared with a 5% theoretical amount of RT. In vitro release profiles and analysis of the obtained data applying different kinetic models revealed Fickian diffusion as the main mechanism of RT release from the SLNs. The morphology of RT-SLNs was characterized by scanning electron microscopy (SEM), whereas the interactions between RT and the lipid matrix were investigated by Raman spectroscopy, evidencing spectral modifications of characteristic bands of RT due to the establishment of new interactions. Finally, antioxidant activity assay on human glioblastoma astrocytoma (U373) culture cells showed a dose-dependent activity for RT-SLNs, particularly at the highest assayed dose (50 μM), whereas the free drug showed the lesser activity.

Kajian Waktu Irigasi pada Tanaman Selada (Lactuva Sativa) Organik Untuk Budidaya Tanaman dengan Naungan dan Tanpa Naungan di Yayasan Bina Sarana Bakti Cisarua Bogor

The Bina Sarana Bakti Foundation (YBSB) implements an organic farming system, which is an agricultural management system with a terrace design with permanent beds that can ecologically (environmentally) improve land quality, provide stable and sustainable yields and income into the future. To provide water for plants so that organic farming can take place throughout the season, both in the rainy season and in the dry season, water reservoirs are built using existing water sources. Utilization of water in the cultivation of organic lettuce at the Bina Sarana Bakti Foundation is carried out with 2-level irrigation hose treatment, namely the interval of providing irrigation water for 3 days and 4 days. Data analysis used t test at 5% real level. The results showed that the theoretical amount of water for lettuce at the Bina Sarana Bakti Foundation was 714 l/bed/season which was almost the same as the actual water use of lettuce with an interval of 3 days of irrigation water including additional liquid fertilizer from rabbit urine. + water in open land in shade is 720 l/bed/season, however, it is much lower than the interval of providing irrigation water for 4 days in open land without shade, namely 4,980 l/bed/season. The production of lettuce in shade with an interval of 3 days of 30.4 kg/bed/season was much greater than the production of lettuce without shade with an interval of 4 days of irrigation water, which was only 24.7 kg/bed/season. The productivity of irrigation water for shaded lettuce with the provision of irrigation water at an interval of 3 days of irrigation is 42.22 kg/m³, much higher and more effective than lettuce without shade with an interval of 4 days of irrigation which is only 4.96 kg/m³. Keywords: irrigation time interval, lettuce plants, no shade, shade, and water productivity.

Centralization impact and cost-saving study in a Moroccan hospital’s centralized unit of chemotherapy preparation

Purpose The purpose of this study was to assess the cost saved and the amount of drug wasted when compounding anticancer drugs in the centralized unit for chemotherapy preparation. A secondary objective was to estimate the centralization impact of activities related to the preparation of chemotherapies. Methods This was a two-month, single-centre, prospective study conducted at the National Oncology Institute in Rabat. The cost saved and the amount of drug wasted were calculated using a standardized data collection sheet (the prescribed dose, the amount of drug deployed, the amount remaining after compounding, the amount of drug saved and the drug wastage). The centralization impact was calculated using the amount of drug wasted in the centralized unit for chemotherapy preparation and a theoretical amount of drug wasted without centralization of preparation. Results During the study period, the total amount of drug saved was 249,959.5 mg (7.2% of drug used), which represented 96,657 USD. The amount of drug wasted was 89,290.5 mg or 42275.5 USD. The drug waste per dilution and per drug was 6.4 mg [1.6-16.1]. While the potential savings over one year (580,000 USD) reached 13.9% of the cytostatic drugs budget for 2018, the potential drug waste cost reached 6.1%. The centralization impact is estimated at an average of 79.5% ± 13.7% waste reduction. Conclusion The outcome of our study showed that the grouping of prescriptions in centralized unit for chemotherapy preparation could result in significant savings on the amount of drugs deployed. The centralization of cytostatic preparations is of economic interest.

Pressure Field Assisted Polycondensation Nonaqueous Precipitation Synthesis of Mullite Whiskers and Their Application as Epoxy Resin Reinforcement

Mullite whiskers were novelty prepared via pressure field assisted polycondensation nonaqueous precipitation method. The precipitate phase transition in heating process, phase compositions and microstructure of samples calcined at different temperatures, effect of pressure field on precursors polycondensation and AlF3 amount on sample morphology, the structure and the growth mechanism of whiskers were investigated. The results indicate that pressure field caused by kettle treatment promotes the polycondensation reaction between AlF3 and tetraethyl orthosilicate (TEOS), the excess aluminum fluoride coordinates with the precipitate skeleton of the =Al–O–Si≡, which brings about the low mullitization temperature (900 °C). The sample prepared with the optimal amount of aluminum fluoride (1.3 of the theoretical amount) calcined at 1100 °C presents high yield and aspect ratio (>15, 100 nm in diameter) of mullite whiskers. Growth of whiskers prepared via pressure field assisted polycondensation nonaqueous precipitation method is attributed to a vapor-solid (VS) mechanism with the inducement of screw. These mullite whiskers with the structure of multi-needle whiskers connected in the same center can be distributed evenly in epoxy resin, which greatly improves the mechanical properties of epoxy resin.

Mathematical models for drug delivery from textile

Gallic acid was microencapsulated in poly-ɛ-caprolactone by the solvent evaporation method and was applied onto biofunctional textile substrates, cotton, and polyamide fabrics using a finishing process. A higher content of microspheres on polyamide was obtained due to the more hydrophobic character of polyamide. Drug release in physiological serum was carried out with treated fabrics submerged into a thermostatized vessel at semi-infinite bath conditions. The kinetic study carried out allowed the determination of the drug-delivery behavior for all systems in the medium. The results showed that the hydrophobicity and affinity of textiles and gallic acid influenced the release mechanism. For cotton, a clear Fickian diffusion was obtained; for polyamide, the diffusion was anomalous. However, no differences were found in the global mass transport. The model could address the need of the medical and health sector for assessing the theoretical amount of drug released from biofunctional textile.