Recent advances in dual-filler mixed matrix membranes

Mixed matrix membranes (MMMs) have been widely developed as an attractive solution to overcome the drawbacks found in most polymer membranes, such as permeability-selectivity trade-off and low physicochemical stability. Numerous fillers based on inorganic, organic, and hybrid materials with various structures including porous or nonporous, and two-dimensional or three-dimensional, have been used. Demanded to further improve the characteristics and performances of the MMMs, the use of dual-filler instead of a single filler has then been proposed, from which multiple effects could be obtained. This article aims to review the recent development of MMMs with dual filler and discuss their performances in diverse potential applications. Challenges in this emerging field and outlook for future research are finally provided.

Effects of M/G Ratios of Sodium Alginate on Physicochemical Stability and Calcium Release Behavior of Pickering Emulsion Stabilized by Calcium Carbonate

The gel properties of sodium alginate (SA) have been revealed to be strongly correlated with its ratio of D-mannuronate to L-guluronate (M/G ratio). Herein, we focused on SA with different M/G ratios to conduct an in-depth study on the effect of the M/G ratio difference on physicochemical stability and calcium release behavior of the Pickering emulsion stabilized by calcium carbonate (CaCO3). The oil phase was added to the aqueous phase, prepared by SA with different M/G ratios (2.23, 0.89, and 0.56) and CaCO3, for one-step shearing to obtain the E1, E2, and E3 emulsions, respectively. The results of the particle size, microstructure, long-term stability, rheological, and microrheological properties of the emulsions showed that the E3 emulsion, prepared by SA with a smaller M/G ratio, had a smaller particle size and has remained in a flow condition during the long-term storage, while the E1 and E2 emulsions had a gelation behavior and a stronger viscoelasticity. Moreover, the emulsion, as a liquid calcium supplement, is not only convenient for oral intake while meeting the calcium needs of the body, but also controls the release of Ca2+. The calcium release of the emulsions in a simulated gastric environment demonstrated that the calcium release ratio increased with the decrease of SA concentration, with the increase of M/G ratio, and with the decrease of oil phase volume.

Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases

Tacrolimus is an immunosuppressant used to treat a large variety of inflammatory or immunity-mediated ophthalmic diseases. However, there are currently no commercial industrial forms available that can provide relief to patients. Various ophthalmic formulations have been reported in the literature, but their stability has only been tested over short periods. The objective of this study was to evaluate the physicochemical stability of a preservative-free tacrolimus formulation (0.2 and 1 mg/mL) at three storage temperatures (5 °C, 25 °C and 35 °C) for up to nine months in a multidose eyedropper. Analyses performed were the following: visual inspection and chromaticity, turbidity, viscosity, size of micelles, osmolality and pH measurements, tacrolimus quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, tacrolimus quantification was also performed on the drops emitted from the eyedroppers. All tested parameters remained stable during the nine month period when the eyedrops were stored at 5 °C. However, during storage at 25 °C and 35 °C, several signs of chemical instability were detected. Furthermore, a leachable compound originating from a silicone part of the eyedropper was detected during the in-use assay. Overall, the 0.2 mg/mL and 1 mg/mL tacrolimus ophthalmic solutions were physicochemically stable for up to nine months when stored at 5 °C.

Stability of 1-unit/mL insulin aspart solution in cyclic olefin copolymer vials and polypropylene syringes

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose This study evaluated the stability of diluted insulin aspart solutions (containing insulin aspart and preservatives) at their most commonly used concentration in intensive care units (1 unit/mL), in 2 container types: cyclic olefin copolymer (COC) vials and polypropylene (PP) syringes. Methods Insulin aspart solution (1 unit/mL, diluted in 0.9% sodium chloride injection) was stored for 365 days in COC vials with gray stoppers and PP syringes at refrigerated (5±3°C) and ambient temperatures (25°C ± 2°C at 60% ± 5% relative humidity and protected from light). Chemical testing was conducted monthly using a validated high-performance liquid chromatography method (quantification of insulin aspart, phenol, and metacresol). Physical stability was evaluated monthly via pH measurements, visible and subvisible particle counts, and osmolality measurements. Sterility testing was also performed to validate the sterile preparation process and the maintenance of sterility throughout the study. Results The limit of stability was set at 90% of the initial concentrations of insulin aspart, phenol, and metacresol. The physicochemical stability of 1-unit/mL insulin solutions stored refrigerated and protected from light, was unchanged in COC vials for the 365-day period and for 1 month in PP syringes. At ambient temperature, subvisible particulate contamination as well as the chemical stability of insulin and metacresol were acceptable for only 1 month’s storage in PP syringes, while insulin chemical stability was maintained for only 3 months’ storage in COC vials. Conclusion According to our results, it is not recommended to administer 1-unit/mL pharmacy-diluted insulin solutions after 3 months’ storage in COC vials at ambient temperature or after 1 month in PP syringes at ambient temperature. The findings support storage of 1-unit/mL insulin aspart solution in COC vials at refrigerated temperature as the best option over the long term. Sterility was maintained in every condition. Both sterility and physicochemical stability are essential to authorize the administration of a parenteral insulin solution.

Stability of Antimicrobials in Elastomeric Pumps: A Systematic Review

Outpatient parenteral antimicrobial therapy (OPAThttp) programs have become an important healthcare tool around the world. Portable elastomeric infusion pumps are functional devices for ambulatory delivery of antimicrobial drugs, and their stability is an essential point to guarantee an appropriate infusion administration. We conducted a systematic review to provide a synthesis and a critical evaluation of the current evidence regarding antimicrobial stability in elastomeric pumps. Data sources were PubMed, EMBASE, and Web of Sciences. The review protocol was registered on the Center for Open Science, and it was carried out following the PRISMA guidelines. Studies were eligible if the aim was the evaluation of the physicochemical stability of an antimicrobial agent stored in an elastomeric device. Of the 613 papers identified, 33 met the inclusion criteria. The most studied group of antimicrobials was penicillins, followed by cephalosporins and carbapenems. In general, the stability results of the antimicrobials that have been studied in more than one article agree with each other, with the exception of ampicillin, flucloxacillin, and ceftazidime. The antibiotics that displayed a longer stability were glycopeptides and clindamycin. Regarding the stability of antifungals and antivirals, only caspofungin, voriconazole, and ganciclovir have been investigated. The information provided in this article should be considered in patient treatments within the OPAT setting. Further stability studies are needed to confirm the appropriate use of the antimicrobials included in this program to ensure optimal patient outcomes.

Extended stability of the trastuzumab biosimilar ABP 980 (KANJINTI™) in polyolefin bags and elastomeric devices

Study Objectives: To investigate the quality and in-use stability of the trastuzumab biosimilar ABP 980 (KANJINTI™) in both concentrated multi-dose bags and following dilution and extended storage in intravenous (IV) bags and elastomeric devices, to address the stability requirements of diff erent global pharmacy practices. Methods: The eff ect of extended refrigerated storage plus exposure to in-use temperature conditions on KANJINTI™ (trastuzumab) solutions was assessed using a range of stability-indicating analytical methods, including appearance, pH, SEC, nonreducing CGE, reducing-CGE, CZE, sub-visible particle counting and potency by a cell-based proliferation inhibition assay. Stability of reconstituted 21 mg/mL solution stored in multi-dose bags and diluted samples at 0.3 mg/mL, 0.8 mg/mL and 4 mg/ mL in 0.9% w/v NaCl solutions stored in IV bags and elastomeric devices was determined over diff erent storage durations. Forced degraded samples exposed to room temperature and natural daylight were used to demonstrate the stability-indicating abilities of the methods. Results: No signifi cant changes were observed in the appearance, pH, monomer concentration, purity, charge heterogeneity, sub-visible particle counts or bioactivity, regardless of initial concentration, container or storage duration. Discussion: There was no indication of signifi cant changes to the physicochemical stability or bioactivity of any of the solutions following extended storage when compared to the initial results acquired on the day of preparation. Conclusion: The data presented has demonstrated the physicochemical stability and bioactivity of a range of KANJINTI™ (trastuzumab) solutions when prepared using controlled and validated aseptic processes, stored protected from light for extended periods at 2°C–8°C and subjected to in-use temperatures. The stability demonstrated in multi-dose bags and elastomeric devices provides additional preparation options to address diff erent global pharmacy practices and requirements.