Development of spray-dried N-acetylcysteine dry powder for inhalation.

N-acetylcysteine (NAC) has both antioxidant and immunomodulatory activities and has been used as adjuvant therapy in several viral infections. Recently, NAC attracted attention for its possible role in reducing the affinity of the spike protein receptor binding domain to angiotensin-converting enzyme (ACE2) receptors. Since only NAC solutions are available for inhalation, the purpose of the work was to develop a NAC dry powder for inhalation using mannitol or leucine as excipient. The powder was successfully produced using co-spray-drying with leucine. ATR-FTIR analyses evidenced spectral variations ascribed to the formation of specific interactions between NAC and leucine. This effect on the NAC environment was not evident for NAC-mannitol powders, but mannitol was in a different polymorphic form compared to the supplied material. Both the feedstock concentration and the leucine content have an impact on the powder aerodynamic features. In particular, to maximize the respirable fraction, it is preferable to produce the powder starting from a 0.5 % w/v feedstock solution using 33 to 50 % w/w leucine content. The NAC-leucine powder was stable for ten months maintaining NAC content of 50 % (w/w) and about 200 µg of NAC was able to deposit on a transwell insert, useful for future in vitro studies.

High dose nanocrystalline solid dispersion powder of voriconazole for inhalation.

In the current work, we aimed to deliver high dose of voriconazole (VRC) to lung through dry powder for inhalation (DPIs). Furthermore, the research tested the hypothesis that drug nanocrystals can escape the clearance mechanisms in lung by virtue of their size and rapid dissolution. High dose nanocrystalline solid dispersion (NCSD) based DPI of VRC was prepared using a novel spray drying process. Mannitol (MAN) and soya lecithin (LEC) were used as crystallization inducer and stabilizer, respectively. The powders were characterized for physicochemical and aerodynamic properties. Chemical interactions contributing to generation and stabilization of VRC nanocrystals in the matrix of MAN were established using computational studies. Performance of NCSD (VRC-N) was compared with microcrystalline solid dispersion (VRC-M) in terms of dissolution, uptake in A549 and RAW 264.7 cells. Plasma and lung distribution of VRC-N and VRC-M in Balb/c mice upon insufflation was compared with the intravenous product. In VRC-N, drug nanocrystals of size 645.86 ± 56.90 nm were successfully produced at VRC loading of 45%. MAN created physical barrier to crystal growth by interacting with N- of triazole and F- of pyrimidine ring of VRC. An increase in drug loading to 60% produced VRC crystals of size 4800 ± 200 nm (VRC-M). The optimized powders were crystalline and showed deposition at stage 2 and 3 in NGI. In comparison to VRC-M, more than 80% of VRC-N dissolved rapidly in around 5-10 mins, therefore, showed higher and lower drug uptake into A549 and RAW 264.7 cells, respectively. In contrast to intravenous product, insufflation of VRC-N and VRC-M led to higher drug concentrations in lung in comparison to plasma. VRC-N showed higher lung AUC0-24 due to escape of macrophage clearance.

New Insights into the Biological Activity of Lichens: Bioavailable Secondary Metabolites of Umbilicaria decussata as Potential Anticoagulants.

This study reports the in vitro anticoagulation activity of acetonic extract (AE) of 42 lichen species and the identification of potential bioavailable anticoagulant compounds from Umbilicaria decussata as a competent anticoagulant lichen species. Lichens' AEs were evaluated for their anticoagulant activity by monitoring activated partial thromboplastin time (APTT) and prothrombin time (PT) assays. A strong, positive correlation was observed between total phenolics concentration (TPC) of species and blood coagulation parameters. U. decussata was the only species with the longest clotting time in both APTT and PT assays. The research was moved forward by performing in vivo assays using rats. The results corroborated the dose-dependent impact of U. decussata's AE on rats' clotting time. Major secondary metabolites of U. decussata and their plasma-related bioavailability were also investigated using LC-ESI-MS/MS. Atranol, orsellinic acid, D-mannitol, lecanoric acid, and evernic acid were detected as possible bioavailable anticoagulants of U. decussata. Our findings suggest that U. decussata might be a potential anticoagulant lichen species that can be used for the prevention or treatment of coagulation-related issues such as cardiovascular diseases (CVDs).

HTK-N: Modified Histidine-Tryptophan-Ketoglutarate Solution-A Promising New Tool in Solid Organ Preservation.

To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.

Improvement of the pharmacokinetic/pharmacodynamic relationship in the treatment of invasive aspergillosis with voriconazole. Reduced drug toxicity through novel rapid release formulations.

Voriconazole (VCZ) is currently the first-line treatment for invasive aspergillosis, although the doses are limited by its poor solubility and high hepatic toxicity. The aim of this study was to develop a solid self-dispersing micellar system of VCZ to improve the pharmacokinetic/pharmacodynamic (PK/PD) relationship and reduce hepatotoxicity. In this work, solid micellar systems of VCZ are formulated with different polysorbate 80 ratios using mannitol as a hydrophilic carrier. The novel micellar systems were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dissolution studies. Self-dispersing micellar systems reduced VCZ crystallinity, leading to an improvement in its dissolution rate. The in vitro susceptibility test also revealed that the most common microorganisms in invasive aspergillosis exhibited low minimum inhibitory concentration (MIC) values for micellar systems. Pharmacokinetic studies indicated an improvement in bioavailability for MS-1:3:0.05, and changes in its biodistribution to different organs. MS-1:3:0.05 showed an increased concentration in lungs and a significant decrease in VCZ accumulated in the liver.

Native starch as in situ binder for continuous twin screw wet granulation.

The use of native starch as in situ binder in a continuous twin screw wet granulation process was studied. Gelatinization of pea starch occurred in the barrel of the granulator using a poorly soluble excipient (anhydrous dicalcium phosphate), but the degree of gelatinization depended on the liquid-to-solid ratio, the granule heating and the screw configuration. Furthermore, the degree of starch gelatinization was correlated with the granule quality: higher binder efficiency was observed in runs where starch was more gelatinized. SEM and PLOM images showed experimental runs which resulted in completely gelatinized starch. Other starch types (maize, potato and wheat starch) could also be gelatinized when processed above a critical barrel temperature for gelatinization. This barrel temperature was different for all starches. In situ starch gelatinization was also investigated in combination with a highly soluble excipient (mannitol). The lower granule friability observed using pure mannitol compared to a mannitol/starch mixture indicated that starch did not contribute to the binding, hence starch did not gelatinize during processing. The study showed that native starch can be considered as a promising in situ binder for continuous twin screw wet granulation of a poorly soluble formulation.

Spray dried curcumin loaded nanoparticles for antimicrobial photodynamic therapy.

Antimicrobial resistance is one of the most serious problems that researchers of multiple disciplines are working on. The number of new antibiotics and their targeted structures have continuously decreased emphasizing the demand of alternative therapy for bacterial infections. Photodynamic therapy is such a promising strategy that has been proven to be effective against a wide range of bacterial strains. In this study, an inhalable nanoformulation for photodynamic therapy against respiratory infections was developed in the form of nano-in-microparticles consisting of curcumin nanoparticles embedded in a mannitol matrix. The produced nano-in-microparticles exhibited suitable aerodynamic properties with a mass median aerodynamic diameter of 2.88 ±â€¯0.13 µm and a high fine particle fraction of 60.99 ±â€¯9.50%. They could be readily redispersed in an aqueous medium producing the original nanoparticles without any substantial changes in their properties. This was confirmed using dynamic light scattering and electron microscopy. Furthermore, the redispersed nanoparticles showed an efficient antibacterial photoactivity causing 99.99992% (6.1log10) and 97.75% (1.6log10) reduction in the viability of Staphylococcus saprophyticus subsp. bovis and Escherichia coli DH5 alpha respectively. Based on these findings, it can be concluded that nano-in-microparticles represent promising drug delivery systems for antimicrobial photodynamic therapy.

Direct compaction properties of Zingiberis Rhizoma extracted powders coated with various shell materials: Improvements and mechanism analysis.

Direct compaction (DC) attracts more and more attention for tablet manufacturing; however, its application in natural plant product (NPP) tablets is still extremely limited. In this study, 8 kinds of composite particles (CPs) based on the Zingiberis Rhizoma extracted powder (ZR) (a natural plant product powder with poor DC properties) were prepared with different shell materials, including hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), dextran, inulin, mannitol, silica, and their combinations. Their physical properties and compacting parameters were characterized comprehensively. The results demonstrated that (i) fluid bed coating was not a simple process of superposition and transmission of the physical properties of raw materials; and (ii) all the shell materials studied could improve the DC properties of problematic ZR to some degree and the combination of 7% HPMC and 1% silica showed to be the best to markedly improve both the compactibility and flowability of ZR. As a whole, by virtue of the design of core-shell particles, qualified tablets with high ZR loadings were successfully produced via continuous DC in this study. These findings are beneficial to boosting the development of natural plant tablets through DC.

Novel Inhalable Ciprofloxacin Dry Powders for Bronchiectasis Therapy: Mannitol-Silk Fibroin Binary Microparticles with High-Payload and Improved Aerosolized Properties.

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease associated with the high morbidity and mortality. Long-term intermittent therapy by inhalable antibiotics has recently emerged as an effective approach for NCFB treatment. However, the effective delivery of antibiotics to the lung requires administering a high dose to the site of infection. Herein, we investigated the novel inhalable silk-based microparticles as a promising approach to deliver high-payload ciprofloxacin (CIP) for NCFB therapy. Silk fibroin (SF) was applied to improve drug-payload and deposit efficiency of the dry powder particles. Mannitol was added as a mucokinetic agent. The dry powder inhaler (DPI) formulations of CIP microparticles were evaluated in vitro in terms of the aerodynamic performance, particle size distribution, drug loading, morphology, and their solid state. The optimal formulation (highest drug loading, 80%) exhibited superior aerosolization performance in terms of fine particle fraction (45.04 ± 0.84%), emitted dose (98.10 ± 1.27%), mass median aerodynamic diameter (3.75 ± 0.03 µm), and geometric standard deviation (1.66 ± 0.10). The improved drug loading was due to the electrostatic interactions between the SF and CIP by adsorption, and the superior aerosolization efficiency would be largely attributed to the fluffy and porous cotton-like property and low-density structure of SF. The presented results indicated the novel inhalable silk-based DPI microparticles of CIP could provide a promising strategy for the treatment of NCFB.

A new therapeutic avenue for bronchiectasis: Dry powder inhaler of ciprofloxacin nanoplex exhibits superior ex vivo mucus permeability and antibacterial efficacy to its native ciprofloxacin counterpart.

Non-cystic fibrosis bronchiectasis (NCFB) characterized by permanent bronchial dilatation and recurrent infections has been clinically managed by long-term intermittent inhaled antibiotic therapy among other treatments. Herein we investigated dry powder inhaler (DPI) formulation of ciprofloxacin (CIP) nanoplex with mannitol/lactose as the excipient for NCFB therapy. The DPI of CIP nanoplex was evaluated against DPI of native CIP in terms of their (1) dissolution characteristics in artificial sputum medium, (2) ex vivo mucus permeability in sputum from NCFB and healthy individuals, (3) antibacterial efficacy in the presence of sputum against clinical Pseudomonas aeruginosa strains (planktonic and biofilm), and (4) cytotoxicity towards human lung epithelial cells. Despite their similarly fast dissolution rates in sputum, the DPI of CIP nanoplex exhibited superior mucus permeability to the native CIP (5-7 times higher) attributed to its built-in ability to generate highly supersaturated CIP concentration in the sputum. The superior mucus permeability led to the CIP nanoplex's higher antibacterial efficacy (>3 log10 CFU/mL). The DPI of CIP nanoplex exhibited similar cytotoxicity towards the lung epithelial cells as the native CIP indicating its low risk of toxicity. These results established the promising potential of DPI of CIP nanoplex as a new therapeutic avenue for NCFB.

Differences in fundamental and functional properties of HPMC co-processed fillers prepared by fluid-bed coating and spray drying.

This study aimed to develop novel co-processed tablet fillers based on the principle of particle engineering for direct compaction and to compare the characteristics of co-processed products obtained by fluid-bed coating and co-spray drying, respectively. Water-soluble mannitol and water-insoluble calcium carbonate were selected as representative fillers for this study. Hydroxypropyl methylcellulose (HPMC), serving as a surface property modifier, was distributed on the surface of primary filler particles via the two co-processing methods. Both fundamental and functional properties of the products were comparatively investigated. The results showed that functional properties of the fillers, like flowability, compactibility, and drug-loading capacity, were effectively improved by both co-processing methods. However, fluid-bed coating showed greater advantages over co-spray drying in some aspects, which was mainly attributed to the remarkable differences in some fundamental properties of co-processed powders, like particle size, surface topology, and particle structure. For example, the more irregular surface and porous structure induced by fluid-bed coating could contribute to better compaction properties and lower lubricant sensitivity due to the increasing contact area and mechanical interlocking between particles under pressure. More effective surface distribution of HPMC during fluid-bed coating was also a contributor. In addition, such a porous agglomerate structure could also reduce the separation of drug and excipients after mixing, resulting in the improvement in drug loading capacity and tablet uniformity. In summary, fluid-bed coating appears to be more promising for co-processing than spray drying in some aspects, and co-processed excipients produced by it have a great prospect for further investigations and development.

Optimization of Acetalated Dextran-Based Nanocomposite Microparticles for Deep Lung Delivery of Therapeutics via Spray-Drying.

Nanocomposite microparticle (nCmP) systems exhibit promising potential in the application of therapeutics for pulmonary drug delivery. This work aimed at identifying the optimal spray-drying condition(s) to prepare nCmP with specific drug delivery properties including small aerodynamic diameter, effective nanoparticle (NP) redispersion upon nCmP exposure to an aqueous solution, high drug loading, and low water content. Acetalated dextran (Ac-Dex) was used to form NPs, curcumin was used as a model drug, and mannitol was the excipient in the nCmP formulation. Box-Behnken design was applied using Design-Expert software for nCmP parameter optimization. NP ratio (NP%) and feed concentration (Fc) are significant parameters that affect the aerodynamic diameters of nCmP systems. NP% is also a significant parameter that affects the drug loading. Fc is the only parameter that influenced the water content of the particles significantly. All nCmP systems could be completely redispersed into the parent NPs, indicating that none of the factors have an influence on this property within the design range. The optimal spray-drying condition to prepare nCmP with a small aerodynamic diameter, redispersion of the NPs, low water content, and high drug loading is 80% NP%, 0.5% Fc, and an inlet temperature lower than 130°C.

Porous mannitol carrier for pulmonary delivery of cyclosporine A nanoparticles.

This study employed the ultrasonic spray-freeze-drying technique to prepare porous mannitol carriers that incorporated hydrophobic cyclosporine A (CsA) nanoparticles (NPs) for pulmonary delivery. Two nanosuspension stabilization systems, (1) a combination of lecithin and lactose system and (2) a D-α-tocopheryl polyethylene glycol succinate (TPGS) system, were investigated. The ability of the lecithin and TPGS in anchoring the hydrophobic CsA NPs to the porous hydrophilic mannitol structure was first reported. Formulations stabilized by TPGS provided a much better dose uniformity, suggesting that TPGS is a better anchoring agent compared with lecithin. The effects of mannitol carrier density and CsA loading (4.9-27%) on aerosol performance and dissolution profiles were assessed. The fine particle fraction (FPF) increased from 44 to 63% as the mannitol concentration decreased from 1 to 5%. All formulations achieved full dissolution within an hour without significant influence from the mannitol content and CsA loading. The initial dissolution rates of the present formulations were almost double than that of the spray-dried counterpart, with 90% of the drug dissolved in 10 min. Overall, the CsA NPs were successfully incorporated into the porous mannitol which demonstrated good aerosol performance and enhanced dissolution profiles. These spray-freeze-drying (SFD) powders were stable after 2-year storage under desiccation at 20 ± 3°C.

Development of protocatechualdehyde proliposomes-based sustained-release pellets with improved bioavailability and desired pharmacokinetic behavior for angina chronotherapy.

The present study was aimed to develope a proliposomal formulation to decrease the hepatic first-pass metabolism of protocatechualdehyde (PD), followed by pellet coating to modify the drug release for angina chronotherapy. PD proliposomes were prepared by depositing PD-phospholipid complex on mannitol powders to improve the drug encapsulation. Afterwards, the PD proliposomes were prepared into pellet cores via extrusion-spheronization using 10% κ-carrageenan as pelletization aid prior to the development of PD sustained-release pellets (PD-SRPs). Eudragit® NE 30D was chosen as coating material and the desired drug release profile of PD-SRPs was calculated for formulation optimization by deconvolution based on the circadian rhythm of variant angina. A high similarity factor (f2=85.72) was achieved when the coating weight was 30% and the sustained release behavior also prevented the destruction of liposomes by gastric fluids. Pharmacokinetic studies revealed a basically consistent trend between the actual and the predicted plasma concentration-time curve with absolute percent errors (%PE) of concentrations <10% in 2-12h. Meanwhile, a relative bioavailability of 200% was achieved compared with pure PD. Therefore, the development of proliposomes-based PD-SRPs was an effective strategy to provide both improved oral bioavailability and desired drug plasma concentration-time course for angina chronotherapy.

Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People.

We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function.

Dry powder inhaler formulation of high-payload antibiotic nanoparticle complex intended for bronchiectasis therapy: Spray drying versus spray freeze drying preparation.

Inhaled nano-antibiotics have recently emerged as the promising bronchiectasis treatment attributed to the higher and more localized antibiotic exposure generated compared to native antibiotics. Antibiotic nanoparticle complex (or nanoplex in short) prepared by self-assembly complexation with polysaccharides addresses the major drawbacks of existing nano-antibiotics by virtue of its high payload and cost-effective preparation. Herein we developed carrier-free dry powder inhaler (DPI) formulations of ciprofloxacin nanoplex by spray drying (SD) and spray freeze drying (SFD). d-Mannitol and l-leucine were used as the drying adjuvant and aerosol dispersion enhancer, respectively. The DPI formulations were evaluated in vitro in terms of the (1) aerosolization efficiency, (2) aqueous reconstitution, (3) antibiotic release, and (4) antimicrobial activity against respiratory pathogen Pseudomonas aeruginosa. The SFD powders exhibited superior aerosolization efficiency to their SD counterparts in terms of emitted dose (92% versus 66%), fine particle fraction (29% versus 23%), and mass median aerodynamic diameter (3 µm versus 6 µm). The superior aerosolization efficiency of the SFD powders was attributed to their large and porous morphology and higher l-leucine content. While the SFD powders exhibited poorer aqueous reconstitution that might jeopardize their mucus penetrating ability, their antibiotic release profile and antimicrobial activity were not adversely affected.

Symbiotic potential and survival of native rhizobia kept on different carriers.

Native rhizobia are ideal for use as commercial legume inoculants. The characteristics of the carrier used to store the inoculants are important for the survival and symbiotic potential of the rhizobia. The objective of this study was to investigate the effects of peat (PEAT), perlite sugarcane bagasse (PSB), carboxymethyl cellulose plus starch (CMCS), and yeast extract mannitol supplemented with mannitol (YEMM) on the survival, nodulation potential and N2 fixation capacity of the native strains Sinorhizobium mexicanum ITTG R7(T) and Rhizobium calliandrae LBP2-1(T) and of the reference strain Rhizobium etli CFN42(T). A factorial design (4 × 3) with four repetitions was used to determine the symbiotic potential of the rhizobial strains. The survival of the strains was higher for PEAT (46% for strain LBP2-1(T), 167% for strain CFN42(T) and 219% for strain ITTG R7(T)) than for the other carriers after 240 days, except for CFN42(T) kept on CMCS (225%). All the strains kept on the different carriers effectively nodulated common bean, with the lowest number of nodules found (5 nodules) when CFN42(T) was kept on CMCS and with the highest number of nodules found (28 nodules) when ITTG R7(T) was kept on PSB. The nitrogenase activity was the highest for ITTG R7(T) kept on PEAT (4911 µmol C2H4 per fresh weight nodule h(-1)); however, no activity was found when the strains were kept on YEMM. Thus, the survival and symbiotic potential of the rhizobia depended on the carrier used to store them.

Symbiotic potential and survival of native rhizobia kept on different carriers

Native rhizobia are ideal for use as commercial legume inoculants. The characteristics of the carrier used to store the inoculants are important for the survival and symbiotic potential of the rhizobia. The objective of this study was to investigate the effects of peat (PEAT), perlite sugarcane bagasse (PSB), carboxymethyl cellulose plus starch (CMCS), and yeast extract mannitol supplemented with mannitol (YEMM) on the survival, nodulation potential and N₂ fixation capacity of the native strains Sinorhizobium mexicanum ITTG R7^T and Rhizobium calliandrae LBP2-1^T and of the reference strain Rhizobium etli CFN42^T. A factorial design (4 × 3) with four repetitions was used to determine the symbiotic potential of the rhizobial strains. The survival of the strains was higher for PEAT (46% for strain LBP2-1^T, 167% for strain CFN42^T and 219% for strain ITTG R7^T) than for the other carriers after 240 days, except for CFN42^T kept on CMCS (225%). All the strains kept on the different carriers effectively nodulated common bean, with the lowest number of nodules found (5 nodules) when CFN42^T was kept on CMCS and with the highest number of nodules found (28 nodules) when ITTG R7^T was kept on PSB. The nitrogenase activity was the highest for ITTG R7^T kept on PEAT (4911 μmol C₂H₄ per fresh weight nodule h⁻¹); however, no activity was found when the strains were kept on YEMM. Thus, the survival and symbiotic potential of the rhizobia depended on the carrier used to store them.

Chemicals from Agave sisalana biomass: isolation and identification.

Agave sisalana (sisal) is known worldwide as a source of hard fibers, and Brazil is the largest producer of sisal. Nonetheless, the process of removing the fibers of the sisal leaf generates 95% waste. In this study, we applied chemical sequential steps (hydrothermal extraction, precipitation, liquid-liquid extraction, crystallization, SiO2 and Sephadex LH 20 column chromatography) to obtain pectin, mannitol, succinic acid, kaempferol and a mixture of saponins as raw chemicals from sisal biomass. The structural identification of these compounds was performed though spectrometric methods, such as Infrared (IR), Ultraviolet (UV), Mass spectrometry (MS) and Nuclear magnetic resonance (NMR). All the sisal chemicals found in this work are used by both the chemical and pharmaceutical industries as excipients or active principles in products.

Encapsulated Lactococcus lactis with enhanced gastrointestinal survival for the development of folate enriched functional foods.

Two lactic acid bacteria (LAB) isolated from cow's milk were identified as Lactococcus lactis strains and designated as L. lactis CM22 and L. lactis CM28. They were immobilised by co-encapsulation using alginate and mannitol and by hybrid entrapment with skim milk, glycerol, CaCO3 and alginate. The encapsulated cells survived better in simulated gastrointestinal conditions compared to the free cells. The percentage survival of probiotics encapsulated by hybrid entrapment method was 62.74% for L. lactis CM22 and 68% for L. lactis CM28. Studies to check their efficacy in fermentative fortification of skim milk and ice cream revealed an enhancement in folate level.