Cocrystal engineering, which involves the self-assembly of two or more components into a solid-state supramolecular structure through non-covalent interactions, has emerged as a promising approach to tailor the physicochemical properties of active pharmaceutical ingredient (API). Efficient coformer screening for cocrystal remains a challenge. Herein, a prediction strategy based on machine learning algorithms was employed to predict cocrystal formation and seven reliable models with accuracy over 0.890 were successfully constructed. Imatinib was selected as the model drug and the models established were applied to screen 31 potential coformers. Experimental verification results indicated RF-8 is the optimal model among seven models with an accuracy of 0.839. When the seven models were combined for coformer screening of Imatinib, the combinational model achieved an accuracy of 0.903, and eight new solid forms were observed and characterized. Benefiting from intermolecular interactions, the obtained multicomponent crystals displayed enhanced physicochemical properties. Dissolution and solubility experiments showed the prepared multicomponent crystals had higher cumulative dissolution rate and remarkably improved the solubility of imatinib, and IM-MC exhibited comparable solubility to Imatinib mesylate α form. Stability test and cytotoxicity results showed that multicomponent crystals exhibited excellent stability and the drug-drug cocrystal IM-5F exhibited higher cytotoxicity than pure API.

Development of prodrugs is a useful strategy to overcome some disadvantages of candidate drugs. Recently, we established a systematic approach to selecting appropriate prodrugs, and validated the utility of this approach using oseltamivir analogues. In this study, the utility of the approach was further examined using candesartan cilexetil and 20 kinds of its analogues having various types of side chain as model compounds. Log D values of analogues (2.5 to 4.7) were higher than that of candesartan (1.0), their active metabolite, and the results were reasonable for the purpose of improving permeability of candesartan. The analogues tended to be more soluble in artificial intestinal fluids than in artificial gastric fluid, owing to their acidic physicochemical characteristics. Their membrane permeabilities were not correlated with log D values, which can be attributed to the metabolism in Caco-2 cells used in this system. In human hepatocytes and enterocytes, 11 out of the 20 analogues were immediately hydrolyzed to candesartan, and species differences were observed in the hydrolysis efficiency. This study confirmed the utility of the systematic approach for selection of appropriate prodrugs that could be proceeded to in vivo pharmacokinetics study, with selection of suitable experimental animals.

Cassava breeding programmes in Uganda do not currently select materials based on flour making quality, explaining in part the low adoption rates of many released varieties. In this study, we describe end user trait preferences, processing qualities and physicochemical properties of cassava flour. We found that higher proportion of women than men showed preference for most attributes of cassava flour quality evaluated in this study. Preference for colour was 66% and 52% among women and men, respectively, while that for stickiness of Kwon was 26% (women) and 15% (men). Ease of peeling and stickiness of Kwon were key processing traits. Heap fermented flour had higher pasting temperatures, but lower viscosities than sun-dried flour, and had lower amylose content compared to fresh root starch. The results demonstrate the importance of gender sensitive participatory evaluation of breeding materials, in tandem with physicochemical evaluation during selection of best possible candidate breeding lines.

Various screening approaches are used by industry to evaluate development risks associated with discovery candidates. This process has become more complicated with biological therapeutics, a class dominated by monoclonal antibodies (mAb), and, increasingly, their derivative constructs. Effective early assessment for drug-like properties (DLP) can save time and costs by allowing a more complete consideration of issues that could impact the desired end result of a stable drug product. Here we report a case study of four IgG1 mAbs, with sequence variations in the variable domain region, screened as a set of possible drug candidates. Our comprehensive, tiered approach used a battery of analytical tools to assess molecular characteristics, conformational stability, colloidal stability, and short-term storage stability. While most DLP for the four candidates were developmentally acceptable and comparable, mAb-2 was associated with adverse colloidal properties. Further investigation of mAb-2 in an expanded pH range revealed a propensity for phase separation, indicating a need for the additional product development effort. Our results support that comprehensive DLP assessments in an expanded pH range are beneficial in identifying development options for promising molecules that show challenging stability trends. This adaptable approach may be especially useful in the development of increasingly complex antibody constructs.

Identification of the biopharmaceutical risks of excipients and excipient variability on oral drug performance can be beneficial for the development of robust oral drug formulations. The current study investigated the impact of Hypromellose (HPMC) presence and varying viscosity type, when used as a binder in immediate release formulations, on the apparent solubility of drugs with wide range of physicochemical properties (drug ionization, drug lipophilicity, drug aqueous solubility). The role of physiological conditions on the impact of excipients on drug apparent solubility was assessed with the use of pharmacopoeia (compendial) and biorelevant media. Presence of HPMC affected drug solubility according to the physicochemical properties of studied compounds. The possible combined effects of polymer adsorption (drug shielding effect) or the formation of a polymeric viscous layer around drug particles may have retarded drug dissolution leading to reduced apparent solubility of highly soluble and/or highly ionized compounds and were pronounced mainly at early time points. Increase in the apparent solubility of poorly soluble low ionized drugs containing a neutral amine group was observed which may relate to enhanced drug solubilization or reduced drug precipitation. The use of multivariate data analysis confirmed the importance of drug physicochemical properties on the impact of excipients on drug apparent solubility and revealed that changes in HPMC material properties or amount may not be critical for oral drug performance when HPMC is used as a binder. The construction of a roadmap combining drug, excipient, and medium characteristics allowed the identification of the cases where HPMC presence may present risks in oral drug performance and bioavailability.

Renaissance of cocrystals as alternative solid forms for fine-tuning physicochemical properties of active pharmaceutical ingredients (APIs) has paved way for development of marketable cocrystals. The current literature reveals established strategies for the design, synthesis and characterization of cocrystals. However, barring a few isolated case studies, strategies for development of cocrystal formulations have been underdeveloped. Herein we report topical formulations of an antioxidant, ferulic acid (FA), which contain the active in its cocrystal form. Cocrystals of FA with the coformers relevant to skin care such as urea, nicotinamide (NA) and isonicotinamide (INA) have been prepared and oleogel formulations of these have been developed. The cocrystal with urea and an anhydrous cocrystal with INA have been identified for the first time in this study. The novel cocrystals were structurally characterized by single crystal X-ray diffraction. Solubility and stability studies have revealed higher solubility of the cocrystals with NA and INA than the parent active and greater stability of FA in formulations that contained the cocrystals with INA and urea than the corresponding formulations containing physical mixtures or parent active. In vitro membrane permeation tests have ascertained sustained release profile of active from the formulation that contained the FA•INA cocrystal. The higher solubility, greater stability and sustained active release profile of the FA•INA cocrystal formulation make it a promising topical formulation of FA.

This work is focused on assessing the potential for the exploitation of used cooking oils (UCOs) as oleochemical feedstock for urban biorefineries. The study case was developed for the city of Bogotá, Colombia. Initially, and according to data from major fats and oils distributors, market information, and public databases, it was estimated that total annual generation of UCOs in Colombia is about 225,000 t, with a per capita of ca. 5 kg/person/yr. Correspondingly, UCOs generation in Bogotá was estimated in at least 45,000 t/yr., with a major generation occurring at Household and HORECA (Hotels, Restaurants and Catering) segments. Specifically in HORECA, fast food restaurants (in particular those of hamburger and chicken) were identified as the main UCOs generators with a suitable supply for industrial exploitation. Then, UCOs samples from this segment of restaurants were subjected to physicochemical characterization by determination of density, volatile matter content, acid value, color, peroxide value, saponification value, iodine value, and content of total polar compounds. The properties associated with the degree of degradation of the oil showed a large variation, even among samples from the same origin. This heterogeneity indicates the need for a pre-treatment process before its reuse. Despite the heterogeneity of the samples, density, iodine value, and saponification value showed slight changes among the different restaurants, largely depending on the nature of the processed cooking oil rather than on the cooking conditions. The collected UCOs showed iodine values and saponification indexes ranging between 80 and 119 g I2/100 g, and 178-201 mg KOH/g, respectively. This indicates that after a suitable purification, UCOs could be used as raw material for a variety of high value oleochemicals. Finally, based upon market data, and to boost further studies, some promissory value-added derivatives are identified.

In the field of ionic liquids (ILs), theory-driven modeling approaches aimed at the best fit for all available data by using a unique, and often nonlinear, model have been widely adopted to develop quantitative structure-property relationship (QSPR) models. In this context, we propose chemoinformatic and chemometric data-driven procedures that lead to QSPR soft models with local validity that are able to predict relevant physicochemical properties of ILs, such as viscosity, density, decomposition temperature, and conductivity. These models, which use readily available and easily interpretable VolSurf+ descriptors, represent an unexploited opportunity for experimentalists to model and predict the physicochemical properties of ILs in industrial R&D design.

Certain farms in Japan, namely unfertilised farms (UFs), have been able to maintain high productivity for over 40 years without applying fertilisers or composts. This study aimed to characterise the physicochemical, biological and micromorphological properties of soil in UFs compared with control farms in Eniwa and Nariita and to identify characteristics that are associated with crop productivity. In UFs, no plough pan was observed. The thickness of the effective soil depth (ESD) of UFs was greater than that of CFs. The concentrations of soil organic carbon, total nitrogen and nitrate-nitrogen in ESD of UFs were higher than those in ESD of CFs. Soil microstructure observations indicated the strong development of a granular microstructure with large amounts of void space and a high fractal dimension in both surface and subsoil horizons of UFs. Dry yield had a strong correlation with ESD thickness and fractal dimension of voids. Thus, the management of unfertilised cultivation promoted the development of soil aggregation in both A and B horizons. The increase in ESD, soil pore spaces and complexity with the development of subsoil structure improved the productivity of unfertilised cultivation.