Improving Tableting Performance of Lactose Monohydrate by Fluid-Bed Melt Granulation Co-Processing

Co-processing is commonly used approach to improve functional characteristics of pharmaceutical excipients to become suitable for tablet production by direct compression. This study aimed to improve tableting characteristics of lactose monohydrate (LMH) by co-processing by fluid-bed melt granulation with addition of hydrophilic (PEG 4000 and poloxamer 188) and lipophilic (glyceryl palmitostearate) meltable binders. In addition to binding purpose, hydrophilic and lipophilic excipients were added to achieve self-lubricating properties of mixture. Co-processed mixtures exhibit superior flow properties compared to pure LMH and comparable or better flowability relative to commercial excipient Ludipress®. Compaction of mixtures co-processed with 20% PEG 4000 and 20% poloxamer 188 resulted in tablets with acceptable tensile strength (>2 MPa) and good lubricating properties (ejection and detachment stress values below 5 MPa) in a wide range of compression pressures. While the best lubricating properties were observed when glyceryl palmitostearate was used as meltable binder, obtained tablets failed to fulfil required mechanical characteristics. Although addition of meltable binder improves interparticle bonding, disintegration time was not prolonged compared to commercial excipient Ludipress®. Co-processed mixtures containing 20% of either PEG 4000 or poloxamer 188 showed superior tabletability and lubricant properties relative to LMH and Ludipress® and can be good candidates for tablet production by direct compression.

UNDERSTANDING EFFECT OF LASER SPEED AND FORMULATION FACTORS ON PRINTABILITY AND CHARACTERISTICS OF SLS IRBESARTAN TABLETS- APPLICATION OF DECISION TREE MODEL 2021ICCBIKG (2021)

Selective laser sintering (SLS) is a rapid prototyping technique for the production of 3D objects through selectively sintering powder-based layers materials by combinations of energy from the laser beam and the heated chamber of the printer. The aim of the study was to investigate the effect of laser speed and formulation factors on printability and characteristics of SLS irbesartan tablets. Physical mixtures of hydroxypropylmethylcellulose (46-91%), Candurin® Gold Sheen (3%), colloidal silicon dioxide (1%), and irbesartan (5%) were prepared. Afterward, crospovidone (1-5%), Kollidon®VA 64 Fine (20%), and/or lactose monohydrate (20-45%) were added. Sintratec Kit SLS printer (Sintratec AG, Switzerland) was used for printing tablets. The decision tree model was applied to classify printability factors. Characterization of tablets was done in terms of physicochemical, mechanical and biopharmaceutical characteristics. Correlation between formulation factors, laser speed, and printability was obtained using decision tree model with an accuracy of 80%. FTIR results revealed that there was no interaction between irbesartan and applied excipients. DSC indicated that irbesartan was present in an amorphous form in printed tablets. It was observed that laser speed had a negative effect on weight. Tuning the drug release by laser speed was possible although lactose monohydrate reduced its impact because it was required higher energy for the sintering process. Results suggest that decision tree could be useful tool for predicting the printability of pharmaceutical formulations. Tailoring characteristics of SLS irbesartan tablets by laser speed is possible, however, it needs to be governed by the composition of the whole formulation.

Combining Co-Amorphous-Based Spray Drying with Inert Carriers to Achieve Improved Bioavailability and Excellent Downstream Manufacturability

It is crucial to improve poorly water-soluble orally administered drugs through both preclinical and therapeutic drug discovery. A co-amorphous formulation consisting of two low molecular weight (MW) molecules offers a solubility/dissolubility advantage over its crystalline form by maintaining their amorphous status. Here, we report on a co-amorphous solid dispersion (SD) system that includes inert carriers (lactose monohydrate or microcrystalline cellulose) and co-amorphous sacubitril (SAC)-valsartan (VAL) using the spray drying process. The strong molecular interactions between drugs were the driving force for forming robust co-amorphous SDs. Our system provided the highest solubility with more than ~11.5- and 3.12-times solubility increases when compared with the physical mixtures. Co-amorphous lactose monohydrate (LM) SDs showed better bioavailability of APIs (~356.27.8% and 154.01% for the relative bioavailability of LBQ 657 and valsartan, respectively). Co-amorphous inert carrier SDs possessed an excellent compressibility for the production of a direct compression pharmaceutical product. In conclusion, these brand-new co-amorphous SDs could reduce the number of unit processes to produce a final pharmaceutical product for downstream manufacturability.

PSV-40 Effects of regrouping and administrations of meloxicam and chromium on plasma cortisol concentrations and behaviors in dairy calves

This study investigated effects of regrouping and oral meloxicam and chromium administration on growth performance, blood cortisol concentrations, and behaviors in dairy calves. Fifty Holstein calves (average age 196 ± 24.7 days, average body weight 198kg ± 32.7 kg) were equally divided into five groups: no regrouping with lactose monohydrate administration (NL), regrouping with lactose monohydrate administration (GL), regrouping with Cr administration (GC), regrouping with meloxicam administration (GM), and regrouping with both meloxicam and Cr administration (GMC). Blood was collected before regrouping and at 3h, 9h, 24h, 1w, and 2w after regrouping. Behaviors have been monitored from d1 to d7. Regrouping did not affect average daily gain (ADG), and the administrations of both meloxicam and chromium increased (P < 0.02) ADG compared to NL group during 2 weeks. Regrouping increased (P < 0.05) plasma cortisol concentrations in GL group, and both meloxicam and chromium and its combination treatments decreased cortisol concentrations compared to GL group at 24h, but not at other times. Regrouping increased (P < 0.05) fight, duration of eating time, head bunt, drinking time, and standing time behaviors in GL group at d1, d2, d2, d3, and d4 respectively. Regrouping also increased (P < 0.05) displacement at eating place in GL group from d3 to d6, but this effect was not significant (P < 0.05) at d7. In conclusion, regrouping caused elevation of plasma cortisol concentrations and abnormal behaviors. Meloxicam, chromium, and/or its combined administrations improved growth performance and reduced circulating cortisol concentrations in regrouped dairy calves, suggesting a feasible strategy to alleviate regrouping stress.