The polymer used in an amorphous solid dispersion (ASD) formulation impacts the maximum achievable drug supersaturation. Herein, the effect of dissolved polymer on drug concentration in the aqueous phase when a drug-rich phase was generated by liquid−liquid phase separation (LLPS) was investigated for different polymers at various concentrations of drug and polymer. Solution nuclear magnetic resonance (NMR) spectroscopy revealed that polyvinylpyrrolidone (PVP), polyvinylpyrrolidone/vinyl acetate (PVP-VA), and hypromellose (HPMC) distributed into the ibuprofen (IBP)-rich phase formed by LLPS when the amorphous solubility of IBP was exceeded. The amount of polymer in the drug-rich phase increased for higher-molecular-weight grades of PVP and HPMC. Moreover, PVP-VA showed a greater extent of distribution into the IBP-rich phase compared to PVP, and this is attributed to its reduced hydrophilicity resulting from the incorporation of vinyl acetate monomers. Direct quantification by NMR measurements indicated that the IBP concentration in the aqueous phase decreased as the amount of polymer in the IBP-rich phase increased. This can be attributed to a reduction of the chemical potential of IBP in the IBP-rich phase. The reduction in dissolved IBP concentration was greater for the IBP/PVP-VA system compared to the IBP/HPMC system, as a result of more extensive drug−polymer interactions in the former system. The present study highlights the impact of polymer selection on the attainable supersaturation of the drug and the factors that need to be considered in the formulation of ASDs to obtain optimized in vivo performance.

In this work, the effect of a biodegradable hydrogel as a seed coating on the early growth of corn seed was studied. The hydrogel was a succinate‐modified potato starch, and it had an equilibrium water absorption capacity of 260 g distilled water (DW)/g hydrogel. To coat corn seeds, the seeds were slightly wetted with an aqueous adhesive solution and then, in a closed container, mixed with a dry mixture of the modified starch (MS), bentonite, and talc. The damp coated seeds were air‐dried at 40 °C for 24 h. The seed emergence and postemergence growth of coated and uncoated seeds were assessed with respect to: (1) the amount of MS on coated seeds, and (2) the available water supply. At a water supply of 77% field capacity (FC), the coated seeds showed a significantly higher rate of emergence than uncoated seeds—however, only a minor improvement was observed at higher and lower water supply levels (92, 82, and 65% FC, respectively). This indicates that, while poor water absorption by hydrogel at low water supply (65% FC) has limited benefit to seed water availability, the effect of good water retention by the hydrogel at high water supply (92, 82% FC) appears redundant in the presence high soil water availability. After 14 and 21 days of growth, the dry weights of the corn plants' roots and shoots did not significantly differ between coated and uncoated seeds, which indicate that, after seed emergence and root development, the contribution of the hydrogel coating to the plant's water requirements becomes negligible. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48523.

This study aims to develop amorphous solid dispersion (ASD) of lumefantrine with a cost-effective approach of spray anti-solvent precipitation. Four acidic polymers, hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), poly(methacrylic acid eethyl acrylate) (EL100) and cellulose acetate phthalate (CAP) were studied as excipients at various drug-polymer ratios. Of the studied polymers, satisfactory physical stability was demonstrated for HPMCP-and HPMCAS-based ASDs with no observed powder X-ray diffraction peaks for up to 3 months of storage at 40 C/75% RH. HPMCP and HPMCAS ASDs also achieved greater drug release levels in the dissolution study than other polymers. The HPMCP-based ASDs with a drug:polymer ratio of 2:8 exhibited a maximum drug release of 140 mg/mL for up to 2 h, which is significantly higher than the currently marketed formulation of Coartem® (<80 ng/mL). Relatively, the CAP and EL100 ASDs indicated a higher water content and crystallized within a day when stored at 40 C/75% RH. The choice of polymer, and the drug-polymer ratio played a crucial role in the solubility enhancement of lumefantrine. Our study indicates that the developed spray anti-solvent precipitation method could be an affordable approach for producing ASDs.

In a spray drying operation, a two-fluid nozzle (2FN) with a single channel is commonly used for atomizing the feed solution. However, the less commonly used three-fluid nozzle (3FN) has two separate channels, which allow spray drying of materials in two incompatible solution systems. Although amorphous solid dispersions (ASDs) prepared using a 3FN have been reported to deliver comparable drug dissolution performance relative to those prepared using a 2FN, few studies have systematically examined the effect of 3FN on the physical stability. Therefore, the goal of this work is to systematically study the physical stability of ASDs that are spray-dried using a 3FN compared to those prepared using the traditional 2FN. For the 2FN, a single solution of naproxen and polyvinylpyrrolidone (PVP) was prepared in a mixture of acetone and water at a 1:1 volume ratio because 2FN allows for only one solution inlet. For the 3FN, naproxen and PVP were dissolved individually in acetone and water, respectively, because 3FN allows simultaneous entry of two solutions. Upon storage of the formulated ASDs at different humidity levels (25%, 55% and 75% RH), naproxen crystallized more quickly from the 3FN ASDs as compared with the 2FN ASDs. 3FN ASDs crystallized after 5 days of storage at all conditions, whereas 2FN ASDs did not crystallize even at 55% RH for two months. This relatively higher crystallization tendency of 3FN ASDs was attributed to the inhomogeneity of drug and polymers as identified by the solid-state Nuclear Magnetic Resonance findings, specifically due to poor mixing of water- and acetone-based solutions at the 3FN nozzle. When only acetone was used as a solvent to prepare drug-polymer solutions for 3FN, the formulated ASD was found to be stable for >3 months of storage (at 75% RH), which suggests that instability of the 3FN ASD was due to the insufficient mixing of water and acetone solutions. This study provides insights into the effects of solvent and nozzle choices on the physical stability of spray-dried ASDs.

No abstract