Defluoridation performance comparison of aluminum hydroxides with different crystalline phases

Aluminum hydroxide is an eye catching and extensively researched adsorbent for fluoride removal and its defluoridation performance is closely related to the preparation method and crystalline phase. In this research, the defluoridation performances of aluminum hydroxides with different crystalline phases are compared and evaluated in terms of fluoride removal capacity, sensitivity to pH values and residual Al contents after defluoridation. It is found that the defluoridation performance of different aluminum hydroxides follows the order of boehmite > bayerite > gibbsite. The fluoride adsorption on aluminum hydroxides follows pseudo-second-order kinetic model and Langmuir isotherm model, and the maximum defluoridation capacities of boehmite, bayerite and gibbsite are 42.08, 2.97 and 2.74 mg m−2, respectively. The pH values and FTIR analyses reveal that the ligand exchange between fluoride and surface hydroxyl groups is the fluoride removal mechanism. Different aluminum hydroxides have different surface hydroxyl group densities, which results in the different defluoridation capacities. This work provides a new idea to prepare aluminum hydroxide with outstanding defluoridation performance.

Compression and morphological properties of a bio-based polyurethane foam with aluminum hydroxide

Compression and morphological evaluation of a new bio-based polyurethane foam (PUF) with aluminum hydroxide (ATH) added as flame retardant were carried out. The PUF was obtained from a blend of vegetable oils. Compression behavior of the polyurethane with different mass fractions of flame retardant (ATH) was investigated according to ASTM D1621–16. The ATH addition highly increased the compression yield strength of the specimens, going from 0.85 MPa (no ATH) to 2.34 MPa ( + 50%wt ATH). The compression yield strain did not show a noteworthy difference up to 40% ATH, presenting a significant decrement in the PUF + 50%ATH. The compression elasticity modulus increased from 15.40 MPa (no ATH) up to 139.77 MPa ( + 50%wt ATH). SEM images were used in order to evaluate the morphological structure of the foam. Regarding the cell sizes, there was no pattern observed, therefore, the cell sizes were adopted as random. The shapes of the cells were detected as elliptical in two different directions in the same cross-sectional area. The digital image correlation (DIC) technique showed higher strain values where the transverse ellipsoid-shaped cells were located, therefore, the load-oriented ellipsoids presented higher stiffness. Thus, the results for PUF with addition of ATH show that the bio-based material presented an important improvement in the compression properties, which allows this material to become more useful for different applications, such as furniture, building and automobile industries, as well as sandwich structures.

Enhancements on Flame Resistance by Inorganic Silicate-Based Intumescent Coating Materials

Flame-retardant coatings have drawn much attention in recent years. In this study, an inorganic sodium silicate-based intumescent flame-resistance coating with an excellent flameproof properties is developed by mainly utilizing sodium silicate as the ceramizable binder, via hydrolysis and self-condensation reaction. Fly ash, metakaoline, and wollastonite behave as supplement cementing materials. Major formulation encompasses the combination of the ammonium polyphosphate and pentaerythritol as the flame-retardant additives, and aluminum hydroxide or expandable graphite as the intumescence-improving filler agents. Expandable graphite was found to play an important role in the eventual performance of flame-resistance testing. The results showed that solid interaction forces can be formed between metakaoline and sodium silicate, resulting in a similar material to geopolymer with excellent physical properties. After high-temperature flame testing, a densely complex protective layer of carbon-char created on top of the robust silicon dioxide networks offers notable flame resistance. An optimal ratio in this inorganic intumescent coating contains sodium silicate—metakaoline (weight ratio = 9:1)—ammonium polyphosphate and pentaerythritol, aluminum hydroxide (3, 3, 10 wt.%)—expandable graphite (1 wt.%), which can create 4.7 times higher expansion ratio compared with neat sodium silicate matrix. The results of flame testing demonstrate only 387.1 °C and 506.3 °C on the back surface of steel substrate after one and three hours flaming (>1000 °C) on the other surface, respectively, which could meet the requirements according to the level of fire rating.

1122. Effect of Aluminum Hydroxide/Magnesium Hydroxide/Simethicone and Omeprazole on the Pharmacokinetics of Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) in Healthy Adult Subjects

Background Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is an oral prodrug that is converted to tebipenem (TBP), the active moiety being developed for treating complication urinary tract infections. Antacids and proton pump inhibitors are known to change gastric pH after administration, which could affect the absorption of oral medications. This study evaluated the effect of a single dose of aluminum hydroxide/magnesium hydroxide/simethicone and the effect of multiple doses of omeprazole on the PK of TBP, following a single dose of TBP-PI-HBr. Methods This was an open-label, 3-period, fixed sequence drug-drug interaction study. On Day 1, Period 1, subjects received a single oral dose of TBP-PI-HBr 600 mg (2 x 300 mg tablets) at Hour 0. On Day 1, Period 2, subjects received a single oral 20 mL dose of aluminum hydroxide 800 mg/magnesium hydroxide 800 mg/simethicone 80 mg suspension per 10 mL (Maalox® Advanced Maximum Strength oral suspension) with a single oral dose of TBP-PI-HBr 600 mg at Hour 0. In Period 3, on Days 1 through 5, subjects received a single oral dose of omeprazole 40 mg (Prilosec®) once daily (QD), at Hour -2. On Day 5, a single oral dose of 600 mg TBP-PI-HBr was administered at Hour 0. Whole blood sampling for TBP PK occurred pre-dose and up to 24 hours post dose. Whole blood samples were assayed for TBP by liquid chromatography-tandem mass spectrometry. Results Twenty subject were enrolled and completed the study. Geometric mean ratios for AUC indicated mean TBP exposure (AUC) was approximately 11% lower and mean Cmax was 22% lower for TBP-PI-HBr combined with aluminum hydroxide/magnesium hydroxide/simethicone vs. TBP-PI-HBr alone (Figure). Similarly, geometric mean ratios for AUC indicated mean TBP exposure (AUC) was approximately 11% lower and mean Cmax was 43% lower for TBP-PI-HBr in combination with omeprazole vs. TBP-PI-HBr alone. Because the PK/PD driver for TBP efficacy is AUC dependent, concomitant administration is not expected to impact the efficacy of oral TBP-PI-HBr. Figure 1. Arithmetic mean plasma TBP concentrations following a 600 mg dose of clinical study drug product (A1 and A2) and registrational drug product (B) – PK population. Conclusion Administration of TBP-PI-HBr combined with aluminum hydroxide/magnesium hydroxide/simethicone or omeprazole QD had no meaningful effect on plasma TBP exposure; Cmax decreased with both agents. Co-administration was generally safe and well tolerated. Disclosures Vipul K. Gupta, Ph.D., Spero Therapeutics (Employee, Shareholder) Gina Patel, PhD, Spero Therapeutics, Inc. (Consultant) Leanne Gasink, MD, Spero Therapeutics, Inc. (Consultant) Floni Bajraktari, MSc, Spero Therapeutics, Inc. (Employee) Yang Lei, PhD, Spero Therapeutics, Inc. (Employee) Akash Jain, PhD, Spero Therapeutics, Inc. (Employee) Praveen Srivastava, MS, BS, Spero Therapeutics, Inc. (Employee) Angela Talley, MD, Spero Therapeutics, Inc. (Employee)

721 Intratumoral immunotherapy with aluminum hydroxide-tethered IL-12 induces potent local and systemic immunity with minimal toxicity

BackgroundInterleukin-12 (IL-12) is a potent pro-inflammatory cytokine that promotes Th1 skewing, IFNγ expression, T- and NK-cell activation, and antigen presentation. In animal models, IL-12 can elicit robust anti-tumor responses through activation of both innate and adaptive immunity. However, clinical translation of IL-12 has been hindered by significant immune-related toxicity when delivered systemically, necessitating low doses that are often insufficient for efficacy. Intratumoral (IT) administration can expand the therapeutic window of IL-12 by increasing the local tumor concentration relative to systemic exposure but is in turn limited by rapid vascular and lymphatic clearance of injected drug from the tumor and corresponding systemic accumulation. Here we describe an approach to locally retain intratumorally administered IL-12 by complexing it to the common vaccine adjuvant aluminum hydroxide (alum) through a novel phosphopeptide linkage.MethodsSingle-chain murine IL-12 (mIL12) was genetically fused at its c-terminus to a short alum-binding peptide (ABP) that is specifically phosphorylated on multiple serines when co-expressed with the kinase Fam20C. Phosphorylated mIL12-ABP proteins were complexed with a 10x mass excess of aluminum hydroxide through a naturally occurring ligand exchange reaction between the phosphoserines in the ABP and surface hydroxyl groups on alum. mIL12-ABP/alum complexes were characterized for in vitro potency and in vivo efficacy in multiple syngeneic tumor models including MC38, CT26, A20, 4T1, and B16F10 following IT administration. Immune analyses and re-challenge experiments are in progress.Results mIL12-ABP is phosphorylated on multiple sites when co-expressed with Fam20C and is stably retained on aluminum hydroxide in vitro under elution conditions containing phosphate and serum. Alum-bound mIL12-ABP remains active in cellular assays with a 3–4 fold increase in EC50 compared to free protein. Following intratumoral administration, the mIL12-ABP/alum complexes have significantly extended tumor retention compared to unmodified mIL12, leading to potent local immune activation for >1 week. One or two doses of IT administered mIL12-ABP/alum is sufficient to induce robust monotherapy efficacy in diverse syngeneic tumor models including cold tumors resistant to checkpoint blockade and other immunotherapies. Locally administered mIL12-ABP/alum is further able to prime a systemic immune response leading to efficacy against non-injected tumors and spontaneous metastases. Doses required for optimal efficacy are well tolerated in mice with no significant weight loss or other evidence of systemic toxicity.ConclusionsAnkyra's platform is a differentiated approach to expand the therapeutic window of IL-12 and other cytokine drugs by enhancing tumor retention following IT administration.