During recent years there have been shortages of certain drugs due to problems in raw material supply. These are often related to active ingredients but could also affect excipients. Lactose is one of the most used excipients in tableting and comes in two anomeric and several solid-state forms. The aim of this study was to utilize lactose from a dairy side-stream and compare it against a commercial reference in direct compression. This would be a sustainable option and would secure domestic availability during crises. Two types of lactose, spray-dried and freeze-dried, were evaluated. Lactose was mixed with microcrystalline cellulose in different ratios together with lubricant and glidant, and flowability and tabletability of the formulations was characterized. The fully amorphous and small particle-sized spray-dried lactose flowed inadequately but exhibited good tabletability. The larger particle-sized, freeze-dried lactose exhibited sufficient flow and better tabletability than the commercial reference. However, disintegration and drug release were slower when using the investigational lactose formulations. This was most likely due to remaining milk proteins, especially caseins, in the lactose. Overall, the investigational lactose provides promise for the use of such a side-stream product during crisis situations but enhancing their properties and/or purity would be needed.

BACKGROUND: The effectiveness of alveolar ridge preservation on bone regeneration and tissue healing has been thoroughly documented in the literature. This study aimed to evaluate the peri-implant soft and hard tissue changes after alveolar ridge preservation using either platelet-rich fibrin (PRF) or freeze-dried bone allograft (FDBA) over a 12-month period following the prosthetic loading of implants.
METHODS: In this randomized clinical trial, 40 individuals were recruited for alveolar ridge preservation using (1) FDBA or (2) PRF in incisal/premolar areas. At two follow-up sessions (six- and 12-months post-implant insertion), radiographic imaging and clinical examinations assessed marginal bone loss and soft tissue factors, including gingival recession and bleeding on probing. The differences between study groups were analyzed using Generalized estimating Equations, the Binary logistic regression model, and Cochran\'s Q test.
RESULTS: There was a statistically significant difference regarding gingival recession at both follow-up evaluations; values in the PRF group were considerably lower compared to the FDBA group (p < 0.05). The mean values for vertical marginal bone loss and bleeding on probing showed no significant differences between the two study groups (p > 0.05).
CONCLUSIONS: Except for gingival recession, applying PRF yielded comparable clinical results to FDBA after one year of implant loading and could be recommended as a potential biomaterial for alveolar ridge preservation following tooth extractions.
BACKGROUND: The research protocol was registered in the Protocol Registration and Results System on 13/08/2021, available at https://clinicaltrials.gov/ (NCT05005377).

Lactobacillus delbrueckii subsp. bulgaricus and Lactiplantibacillus plantarum are two lactic acid bacteria (LAB) widely used in the food industry. The objective of this work was to assess the resistance of these bacteria to freeze- and spray-drying and study the mechanisms involved in their loss of activity. The culturability and acidifying activity were measured to determine the specific acidifying activity, while membrane integrity was studied by flow cytometry. The glass transitions temperature and the water activity of the dried bacterial suspensions were also determined. Fourier transform infrared (FTIR) micro-spectroscopy was used to study the biochemical composition of cells in an aqueous environment. All experiments were performed after freezing, drying and storage at 4, 23 and 37 °C. The results showed that Lb. bulgaricus CFL1 was sensitive to osmotic, mechanical, and thermal stresses, while Lpb. plantarum WCFS1 tolerated better the first two types of stress but was more sensitive to thermal stress. Moreover, FTIR results suggested that the sensitivity of Lb. bulgaricus CFL1 to freeze-drying could be attributed to membrane and cell wall degradation, whereas changes in nucleic acids and proteins would be responsible of heat inactivation of both strains associated with spray-drying. According to the activation energy values (47-85 kJ/mol), the functionality loss during storage is a chemically limited reaction. Still, the physical properties of the glassy matrix played a fundamental role in the rates of loss of activity and showed that a glass transition temperature 40 °C above the storage temperature is needed to reach good preservation during storage. KEY POINTS: • Specific FTIR bands are proposed as markers of osmotic, mechanic and thermal stress • Lb. bulgaricus CFL1 was sensitive to all three stresses, Lpb. plantarum WCFS1 to thermal stress only • Activation energy revealed chemically limited reactions ruled the activity loss in storage.

Direct imaging of semi-solid lipids, such as myelin, is of great interest as a noninvasive biomarker of neurodegenerative diseases. Yet, the short T2 relaxation times of semi-solid lipid protons hamper direct detection through conventional magnetic resonance imaging (MRI) pulse sequences. In this study, we examined whether a three-dimensional ultrashort echo time (3D UTE) sequence can directly acquire signals from membrane lipids. Membrane lipids from red blood cells (RBC) were collected from commercially available blood as a general model of the myelin lipid bilayer and subjected to D2O exchange and freeze-drying for complete water removal. Sufficiently high MR signals were detected with the 3D UTE sequence, which showed an ultrashort T2* of ∼77-271 µs and a short T1 of ∼189 ms for semi-solid RBC membrane lipids. These measurements can guide designing UTE-based sequences for direct in vivo imaging of membrane lipids.

Dendrobium officinale flower tea (DFT) is a traditional health product of geographical identity known for its unique aroma and taste. The effects of different drying methods on sensory properties, metabolic profiles and antioxidant activity of DFT were compared using sensomics and metabolomics approaches. Twenty-seven aroma-active compounds were identified and more than half of the volatiles responsible for the \"green\" and \"floral\" scent lost after drying. Sensory evaluations revealed that vacuum freeze-dried DFT showed a significant preference in taste and fifty-eight metabolites with higher levels of glutamine were observed, possibly contributing to a \"fresh\" taste and increased preference. Among the three drying methods, natural air drying retained the fresh flower scent better, while freeze drying preserved the color and shape of the flowers better and enhanced the taste and antioxidant activity of DFT. The research results may provide a foundation for the selection of DFT processing method and quality detection.

In this study, we present the lyophilization process development efforts for a vaccine formulation aimed at optimizing the primary drying time (hence, the total cycle length) through comprehensive evaluation of its thermal characteristics, temperature profile, and critical quality attributes (CQAs). Differential scanning calorimetry (DSC) and freeze-drying microscopy (FDM) were used to experimentally determine the product-critical temperatures, viz., the glass transition temperature (Tg\') and the collapse temperature (Tc). Initial lyophilization studies indicated that the conventional approach of targeting product temperature (Tp) below the Tc (determined from FDM) resulted in long and sub-optimal drying times. Interestingly, aggressive drying conditions where the product temperature reached the total collapse temperature did not result in macroscopic collapse but, instead, reduced the drying time by ∼ 45 % while maintaining product quality requirements. This observation suggests the need for a more reliable measurement of the macroscopic collapse temperature for product in vials. The temperature profiles from different lyophilization runs showed a drop in product temperature following the primary drying ramp, of which the magnitude was correlated to the degree of macroscopic collapse. The batch-average product resistance, Rp, determined using the manometric temperature measurement (MTM), decreased with increasing dried layer thickness for aggressive primary drying conditions. A quantitative analysis of the product temperature and resistance profiles combined with qualitative assessment of cake appearance attributes was used to determine a more representative macro-collapse temperature, Tcm, for this vaccine product. A primary drying design space was generated using first principles modeling of heat and mass transfer to enable selection of optimum process parameters and reduce the number of exploratory lyophilization runs. Overall, the study highlights the importance of accurate determination of macroscopic collapse in vials, pursuing aggressive drying based on individual product characteristics, and leveraging experimental and modeling techniques for process optimization.

BACKGROUND: Chondroprogenitors, with enhanced chondrogenic potential, have emerged to be a promising alternative for cell-based therapy in cartilage repair. Platelet-rich plasma (PRP), widely used for intra-articular treatment, has a short half-life. Freeze-dried PRP (FD-PRP), with an extended half-life and retained growth factors, is gaining attention. This study compares the efficacy of Migratory Chondroprogenitors (MCPs) in gelled PRP and FD-PRP using in-vitro and ex-vivo models, assessing FD-PRP as a potential off-the-shelf option for effective cartilage repair.
METHODS: MCPs were isolated from osteoarthritic cartilage samples (n = 3), characterized through FACS and RT-PCR. For in-vitro analysis, cells were loaded into gelled PRP and FD-PRP scaffolds at a density of 1x106 cells per scaffold. Trilineage differentiation studies and live-dead assays were conducted on MCPs using Calcein AM/Propidium Homodimer-1. In ex-vivo analysis, MCPs of the same density were added to Osteochondral Units (OCU) with chondral defects containing PRP gel and FD-PRP scaffolds, harvested on the 15th and 35th days for histological examination. Controls included cell-free scaffolds.
RESULTS: Our in-vitro analysis demonstrates the robust viability of MCPs in both scaffolds, with no discernible impact on their differentiation capacity. Ex-vivo analysis of the OCU for cartilage repair showed that the chondrogenic potential characterized by the accumulation of extracellular matrix containing glycosaminoglycans and collagen type II production (with no alteration in collagen type X), was observed to be better with the gel PRP and the gel PRP containing MCP groups.
CONCLUSIONS: These findings support the preference for gel PRP as a superior synergistic scaffold for chondroprogenitor delivery.

The challenge of preserving the quality of thermal-sensitive polymeric materials specifically proteins during a thermal drying process has been a subject of ongoing concern. To address this issue, we investigated the use of ultrasound contact drying (USD) under non-thermal conditions to produce functionalized pea protein powders. The study extensively examined functional and physicochemical properties of pea protein isolate (PPI) in powder forms obtained through three drying methods: USD (30 °C), spray drying (SD), and freeze drying (FD). Additionally, physical attributes such as powder flowability and color, along with morphological properties, were thoroughly studied. The results indicated that the innovative USD method produced powders of comparable quality to FD and significantly outperformed SD. Notably, the USD-PPI exhibited higher solubility across all pH levels compared to both FD-PPI and SD-PPI. Moreover, the USD-PPI samples demonstrated improved emulsifying and foaming properties, a higher percentage of random coil form (56.2 %), increased gel strength, and the highest bulk and tapped densities. Furthermore, the USD-PPI displayed a unique surface morphology with visible porosity and lumpiness. Overall, this study confirms the effectiveness of non-thermal ultrasound contact drying technology in producing superior functionalized plant protein powders, showing its potential in the fields of chemistry and sustainable materials processing.

This study focused into vacuum freeze dryer technology for increasing food shelf life in a drying food technology. The determinants of energy consumption increase as the energy density of food production and storage increases. Reducing the amount of energy used for drying, freezing, chilling, refrigeration, and air conditioning is becoming more important. The objective of this study was to extend food\'s shelf life utilizing creative and novel technical approaches, such as vacuum freeze-drying\'s energy-efficient process. Despite being a part of this investigation, the vacuum freeze drier was created using environmentally benign energy sources. To minimize the carbon footprint of food preservation, it is essential to use eco-friendly energy sources in chilling storage. According to the first law of thermodynamics, the energy efficiency at 1 atm pressure and 25 [°C] temperature (neglecting potential and kinetic energies) in the dead state is calculated under thermal equilibrium conditions. In this study, the energy efficiency was shown according to 5 different scenarios. The results of energy efficiencies are as follows: η1 is from 14.3 to 21.4%, η2 is from 20.7 to 31.0%, η3 is from 27.3 to 40.9%, η4 is from 32.1 to 48.1%, and η5 is from 34.6 to 51.9%, respectively. This analysis demonstrates that the energy efficiency improved from 12 to 18 h. In this study, optimizations with scenarios were employed considering vacuum freeze-drying technology in the plant with sustainable energy sources can considerably improve food shelf life while limiting our environmental impact.

The primary aim of this study was to assess the histomorphometric outcomes of extraction sockets grafted with freeze-dried bone allograft (FDBA) and sealed with a collagen membrane after 3 months of healing in specific region of interest (ROI) areas. The secondary aims were to analyze the biomaterial resorption rate, the bone-to-biomaterial contact (BBC), and the area and perimeter of grafted particles compared with commercially available FDBA particles. Fifteen patients underwent tooth extractions and ridge preservation procedures performed with FDBA and a collagen membrane. Bone biopsy samples were harvested after 3 months at the time of implant placement for histologic and histomorphometric analysis. Two areas of concern (ROI1 and ROI2) with different histologic features were identified within the biopsy samples; ROI1, ROI2, and commercially available particles were analyzed and compared. The following parameters were analyzed: newly formed bone, marrow space, residual graft particles, perimeter and area of FDBA particles, and BBC. The histomorphometric analysis showed 35.22% ± 10.79% newly formed bone, 52.55% ± 16.06% marrow spaces, and 12.41% ± 7.87% residual graft particles. Moreover, the histologic data from ROI1 and ROI2 showed that (1) the mean percentage of BBC was 64.61% ± 27.14%; (2) the newly formed bone was significantly higher in ROI1 than in ROI2; (3) the marrow space was significantly lower in ROI1 than in ROI2; and (4) the FDBA particles in ROI1 sites showed significantly lower area and perimeter when compared to commercially available FDBA particles. This latter data led to the hypothesis that FDBA particles embedded in newly formed bone undergo a resorption/remodeling process.