Balancing earliness and tardiness within workload control order release: an assessment by simulation

Most Workload Control literature assumes that delivery performance is determined by tardiness related performance measures only. While this may be true for companies that directly deliver to end-customers, for make-to-stock companies or firms that are part of supply chains, producing early often means large inventories in the finished goods warehouse or penalties incurred by companies downstream in the supply chain. Some earlier Workload Control studies used a so-called time limit, which constrains the set of jobs that can be considered for order release, to reduce earliness. However, recent literature largely abandoned the time limit since it negatively impacts tardiness performance. This study revisits the time limit, assessing the use of different adaptive policies that restrict its use to periods of either low or high load. By using a simulation model of a pure job shop, the study shows that an adaptive policy allows to balance the contradictory objectives of delaying the release of orders to reduce earliness and to release orders early to respond to periods of high load as quick as possible. Meanwhile, only using a time limit in periods of high load was found to be the best policy.

Tailoring α/β Ratio of Pollen-Like Anhydrous Lactose as Ingredient Carriers for Controlled Dissolution Rate

Lactose is a commonly used excipient with two isomers. Different isomers have different properties, especially in terms of solubility. This work is mainly to explore the influence of different a/β ratio lactose on drug dissolution. This work has developed novel mesoporous pollen-like lactose anhydrous with tailored α/β ratios as ingredient carriers for controlled dissolution rate. The produced lactose carriers are pollen-like with a particle size of ~15 μm and a mean pore width of ~30 nm. β-lactose anhydrous has a unique FTIR-peak at 948 cm−1, whereas α-lactose anhydrous shows a unique FTIR-peak at 855 cm−1. DSC analysis suggests that the pollen-like α/β-lactose crystals are polymorphs with unique peaks of melting points. XRD analysis suggests that (5:5)α/β-lactose polymorph has high crystalline purity. The loading efficiency (30.6–33.4% w/w) of acetamidophenol within the nanoporous lactose particles is dependent on the surface structure and pore volumes—the pore volumes were found to be 0.0209–0.0380 cm3/g. The release rates of acetamidophenol are lower for lactose with high α/β ratios. The lactose solubility and the first-order release constant can be tailored by changing the proportion of β-lactose in the pollen-like lactose carriers.

Different Approaches to the Synthesis and Applications of Biomedical and Pharmaceutical Smart Biomaterials

In this study, two strategies were used to functionalize cellulose nanowhiskers. Firstly, by grafting its surface with β-cyclodextrin (βCD) for developing drug-nanocarrier. Secondly, by conjugating short polymer segments to its surface for reinforcing Poly(Ɛ-Caprolactone) (PCL), in order to develop nanocomposites with promoted properties suitable for regenerative medicine. In addition, the production and recovery of biodegradable bioplastics poly(3-hydroxybutyrate) (P(3HB)) from agro-industrial residues of hemp hurd biomass was also examined. In the first part, a drug-nanocarrier system based on βCD-grafted bacterial cellulose nanowhisker (BCNC-g-βCD) was developed as a prolonged drug release nanocarrier. Antibiotic Ciprofloxacin (CIP) and anticancer drugs; Doxorubicin (DOX) and Paclitaxel (PTX) were conjugated to BCNC-g-βCD as model drugs to form the drug-nanocarrier (BCNC-g-βCD-drug). Compared with un-grafted BCNC, the developed drug-nanocarrier showed significant increase in drug payloads from 495 ±4 to 810 ±7 µg/mg along with radical improvement in the drug release profiles. Initial burst releases was reduced significantly and prolonged and sustained release for (74.5–90%) of drug payload over 4–5.5 days were observed. In addition, an improved drug release performances were pragmatic in acidic pH of 6.4 that mimicked extracellular tumor cells. In vitro drug release data pointed to zero-order kinetic model with estimated zero-order release constants (K0) of 0.68, 0.74, and 0.79 µg drug/h (at pH 6.4, 37°C) for BCNC-g-βCD-CIP, BCNC-g-βCD-DOX and BCNC-g-βCD-PTX nanosystems, respectively. In the second part, the functionalized bacterial cellulose nanowhisker (BCNW-g-βCD-PCL2000) was synthesized. Reinforcing PCL matrix with 4 wt% of the functionalized nanowhisker resulted in bionanocomposite with promoted bulk properties. Compared to neat PCL, the obtained bionanocomposite showed 115% and 51% improvements in tensile strength and Young’s modulus, respectively; 20% increase in hydrophilicity; 7% increase in degradation rate; and 6% decrease in crystallinity. Gas foaming/combined particulate leaching technique is used to develop highly porous strutures having porosity of 86-95% and interconnected macropores with mean pore diameters of 250-420 µm. Porous scaffolds showed compression moduli values of 5.3-9.1 MPa in the range of cancellous bones. In the third part a dual-function PCL scaffold was fabricated. The envisioned drug-laden scaffold would provide adequate structural and mechanical supports for the newly regenerated tissues and simultaneously serve as localized drug delivery system. In this context, reinforced PCL with 4 wt% of BCNW-g-βCD-PCL2000 and 25 wt% of doxorubicin anticancer drug resulted in drugladen bionanocomposite of combined promoted bulk properties. Improvements of 165% and 107% in tensile strength and Young’s modulus, respectively; 31% in hydrophilicity; 10% in degradation rate; and 8°C increases in thermal stability. The obtained drug-laden porous scaffolds showed compressive moduli in the range of 7.2-12.3 MPa. In vitro drug releases fit the first-order release mechanism and occurred in a diffusion-controlled and sustained manner 60 days without obvious burst releases. The scaffolds will ultimately minimize systemic toxicities of drugs, lessen the number of dosing, and diminish the need for removal procedure. The forth study described prospective trials for greener production and extraction of the biodegradable bioplastics poly(3-hydroxybutyrate) P(3HB) from agro-industrial residues of hemp hurd biomass. Results showed that maximum hydrolysis yield of 72.4% was achieved by alkali pretreatment with 2% NaOH at 135°C for 60 min along with two-step enzymatic hydrolysis and ultrasonication. Total hydrolysate sugar concentration of 53.0 g/L was obtained. Under optimum conditions, total P(3HB) production of 13.4 g/L was achieved within 80 h of fermentation. Ultrasonic-assisted sodium dodecyl sulfate (SDS) has showed effectiveness as economic recovery method. It recovered bioplastics directly from the broth cell concentrate with P(3HB) content of 92%. Number average molecular weights (Mn) of recovered bioplastics were in the range of 150–270 kDa with polydispersity index (Mw/Mn) of 2.1–2.4.

Different Approaches to the Synthesis and Applications of Biomedical and Pharmaceutical Smart Biomaterials

In this study, two strategies were used to functionalize cellulose nanowhiskers. Firstly, by grafting its surface with β-cyclodextrin (βCD) for developing drug-nanocarrier. Secondly, by conjugating short polymer segments to its surface for reinforcing Poly(Ɛ-Caprolactone) (PCL), in order to develop nanocomposites with promoted properties suitable for regenerative medicine. In addition, the production and recovery of biodegradable bioplastics poly(3-hydroxybutyrate) (P(3HB)) from agro-industrial residues of hemp hurd biomass was also examined. In the first part, a drug-nanocarrier system based on βCD-grafted bacterial cellulose nanowhisker (BCNC-g-βCD) was developed as a prolonged drug release nanocarrier. Antibiotic Ciprofloxacin (CIP) and anticancer drugs; Doxorubicin (DOX) and Paclitaxel (PTX) were conjugated to BCNC-g-βCD as model drugs to form the drug-nanocarrier (BCNC-g-βCD-drug). Compared with un-grafted BCNC, the developed drug-nanocarrier showed significant increase in drug payloads from 495 ±4 to 810 ±7 µg/mg along with radical improvement in the drug release profiles. Initial burst releases was reduced significantly and prolonged and sustained release for (74.5–90%) of drug payload over 4–5.5 days were observed. In addition, an improved drug release performances were pragmatic in acidic pH of 6.4 that mimicked extracellular tumor cells. In vitro drug release data pointed to zero-order kinetic model with estimated zero-order release constants (K0) of 0.68, 0.74, and 0.79 µg drug/h (at pH 6.4, 37°C) for BCNC-g-βCD-CIP, BCNC-g-βCD-DOX and BCNC-g-βCD-PTX nanosystems, respectively. In the second part, the functionalized bacterial cellulose nanowhisker (BCNW-g-βCD-PCL2000) was synthesized. Reinforcing PCL matrix with 4 wt% of the functionalized nanowhisker resulted in bionanocomposite with promoted bulk properties. Compared to neat PCL, the obtained bionanocomposite showed 115% and 51% improvements in tensile strength and Young’s modulus, respectively; 20% increase in hydrophilicity; 7% increase in degradation rate; and 6% decrease in crystallinity. Gas foaming/combined particulate leaching technique is used to develop highly porous strutures having porosity of 86-95% and interconnected macropores with mean pore diameters of 250-420 µm. Porous scaffolds showed compression moduli values of 5.3-9.1 MPa in the range of cancellous bones. In the third part a dual-function PCL scaffold was fabricated. The envisioned drug-laden scaffold would provide adequate structural and mechanical supports for the newly regenerated tissues and simultaneously serve as localized drug delivery system. In this context, reinforced PCL with 4 wt% of BCNW-g-βCD-PCL2000 and 25 wt% of doxorubicin anticancer drug resulted in drugladen bionanocomposite of combined promoted bulk properties. Improvements of 165% and 107% in tensile strength and Young’s modulus, respectively; 31% in hydrophilicity; 10% in degradation rate; and 8°C increases in thermal stability. The obtained drug-laden porous scaffolds showed compressive moduli in the range of 7.2-12.3 MPa. In vitro drug releases fit the first-order release mechanism and occurred in a diffusion-controlled and sustained manner 60 days without obvious burst releases. The scaffolds will ultimately minimize systemic toxicities of drugs, lessen the number of dosing, and diminish the need for removal procedure. The forth study described prospective trials for greener production and extraction of the biodegradable bioplastics poly(3-hydroxybutyrate) P(3HB) from agro-industrial residues of hemp hurd biomass. Results showed that maximum hydrolysis yield of 72.4% was achieved by alkali pretreatment with 2% NaOH at 135°C for 60 min along with two-step enzymatic hydrolysis and ultrasonication. Total hydrolysate sugar concentration of 53.0 g/L was obtained. Under optimum conditions, total P(3HB) production of 13.4 g/L was achieved within 80 h of fermentation. Ultrasonic-assisted sodium dodecyl sulfate (SDS) has showed effectiveness as economic recovery method. It recovered bioplastics directly from the broth cell concentrate with P(3HB) content of 92%. Number average molecular weights (Mn) of recovered bioplastics were in the range of 150–270 kDa with polydispersity index (Mw/Mn) of 2.1–2.4.