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Study of the influence of both cyclodextrins and L-lysine on the aqueous solubility of nimesulide; isolation and characterization of nimesulide-L-lysine-cyclodextrin complexes.

Nimesulide is a nonsteroidal antiinflammatory drug that exhibits a very poor water solubility (0.01 mg.mL-1). A nimesulide-beta-cyclodextrin complex prepared according to patent application WO 94/ 02177 has an aqueous solubility of approximately 16 mg.mL-1 of nimesulide. A nimesulide-L-lysine salt has also been prepared and increases the aqueous solubility of nimesulide to approximately 5.0-7.5 mg.mL-1. The purpose of the present study was to investigate the interaction of both cyclodextrins and L-lysine on the aqueous solubility of nimesulide. Nimesulide-L-lysine-beta- or gamma-cyclodextrin complexes were prepared by spray-drying. The inclusion of the nimesulide-L-lysine salt into the cyclodextrin cavity was confirmed by differential scanning calorimetry and proton nuclear magnetic resonance spectroscopy. These complexes offered remarkable aqueous solubility. The incorporation of nimesulide in a nimesulide-L-lysine-beta-cyclodextrin complex increased its water solubility by a factor of 10 at pH 1.5 (0.050 mg.mL-1 for the complex versus 0.005 mg.mL-1 for nimesulide), 160 at pH 6.8 (2.373 mg.mL-1 for the complex versus 0.015 mg.mL-1 for nimesulide), and 3600 in purified water (36.400 mg.mL-1 for the complex versus 0.01 mg.mL-1 for nimesulide).

Anti-Inflammatory Agents, Non-Steroidal↗

Characterization of tolbutamide polymorphs (Burger's forms II and IV) and polymorphic transition behavior.

Burger's two polymorphs of tolbutamide (TB), an oral hypoglycemic agent, were obtained by spray-drying the drug dissolved in a mixed solvent of ethanol/dichloromethane (Form IV) and allowing Form IV to stand at constant temperatures and humidities (Form II). These polymorphs were characterized by various physical methods [e.g., powder X-ray diffractometry, differential scanning calorimetry, infrared spectrometry, and solid-state carbon-13 nuclear magnetic resonance (13C NMR) spectroscopy] and compared with two other TB polymorphs Forms I and III. The 13C NMR spectra showed that the chemical shift and the peak shape of resonance associated with the toluene and n-butyl moieties of TB were different for each of the four polymorphs, whereas the carbonyl carbon was unchanged, indicating different conformations and molecular motions of the toluene and n-butyl moieties in the solid states. Form IV converted itself to Form II within 3 h when it was stored at 45 degrees C and 75% relative humidity (RH) and, in turn, Form II transformed to Form I at higher temperatures. The conversion of Form IV to Form II proceeded according to a zero-order equation (Polany-Winger equation), and that of Form II to Form I according to a first-order equation. The increase in RH accelerated the polymorphic transition of Form IV. Both the apparent dissolution rate and the solubility of Form IV were nearly identical with those of Form II, because the former changed to the latter during the dissolution, but their dissolution rates and solubility were higher than those of Forms I and III. These dissolution characteristics of TB polymorphs were reflected in the oral absorption behavior in dogs; that is, the bioavailability increased in the order Form I < Form III < Form II approximately Form IV.

Animals↗

Hollow porous particles in metered dose inhalers.

PURPOSE: To assess the physical stability and aerosol characteristics of suspensions of hollow porous microspheres (PulmoSpheres) in HFA-134a. METHODS: Cromolyn sodium, albuterol sulfate, and formoterol fumarate microspheres were prepared by a spray-drying method. Particle size and morphology were determined via electron microscopy. Particle aggregation and suspension creaming times were assessed visually, and aerosol performance was determined via Andersen cascade impaction and dose uniformity studies. RESULTS: The hollow porous particle morphology allows the propellant to permeate freely within the particles creating a novel form of suspension termed a homodispersion, wherein the dispersed and continuous phases are identical, separated by an insoluble interfacial layer of drug and excipient. Homodispersion formation improves suspension stability by minimizing the difference in density between the particles and the medium, and by reducing attractive forces between particles. The improved physical stability leads to excellent dose uniformity. Excellent aerosolization efficiencies are also observed with PulmoSpheres formulations, with fine particle fractions of about 70%. CONCLUSIONS: The formation of hollow porous particles provides a new formulation technology for stabilizing suspensions of drugs in hydrofluoroalkane propellants with improved physical stability, content uniformity, and aerosolization efficiency.

Administration, Inhalation↗

Novel lipid-based hollow-porous microparticles as a platform for immunoglobulin delivery to the respiratory tract.

PURPOSE: Delivery of specific antibodies or immunoglobulin constructs to the respiratory tract may be useful for prophylaxis or active treatment of local or systemic disorders. Therefore, we evaluated the utility of lipid-based hollow-porous microparticles (PulmoSpheres) as a potential delivery vehicle for immunoglobulins. METHODS: Lipid-based microparticles loaded with human immunoglobulin (hIgG) or control peptide were synthesized by spray drying and tested for: i) the kinetics of peptide/protein release, using ELISA and bioassays; ii) bioavailability subsequent to nonaqueous liquid instillation into the respiratory tract of BALB/c mice, using ELISA and Western blotting; iii) bioactivity in terms of murine immune response to xenotypic epitopes on human IgG, using ELISA and T cell assays; and iv) mechanisms responsible for the observed enhancement of immune responses, using measurement of antibodies as well as tagged probes. RESULTS: Human IgG and the control peptide were both readily released from the hollow-porous microspheres once added to an aqueous environment, although the kinetics depended on the compound. Nonaqueous liquid instillation of hIgG formulated in PulmoSpheres into the upper and lower respiratory tract of BALB/c mice resulted in systemic biodistribution. The formulated human IgG triggered enhanced local and systemic immune responses against xenotypic epitopes and was associated with receptor-mediated loading of alveolar macrophages. CONCLUSIONS: Formulation of immunoglobulins in hollow-porous microparticles is compatible with local and systemic delivery via the respiratory mucosa and may be used as means to trigger or modulate immune responses.

Administration, Inhalation↗

The use of inverse phase gas chromatography to measure the surface energy of crystalline, amorphous, and recently milled lactose.

PURPOSE: To assess differences in surface energy due to processing induced disorder and to understand whether the disorder dominated the surfaces of particles. METHODS: Inverse gas chromatography was used to compare the surface energies of crystalline, amorphous, and ball milled lactose. RESULTS: The milling process made ca 1% of the lactose amorphous, however the dispersive contribution to surface energy was 31.2, 37.1, and 41.6 mJ m(-2) for crystalline, spray dried and milled lactose, respectively. A physical mixture of crystalline (99%) and amorphous (1%) material had a dispersive surface energy of 31.5 mJ m(-2). CONCLUSION: Milling had made the surface energy similar to that of the amorphous material in a manner that was very different to a physical mixture of the same amorphous content. The milled material will have similar interfacial interactions to the 100% amorphous material.

Algorithms↗

Improving stability and release kinetics of microencapsulated tetanus toxoid by co-encapsulation of additives.

PURPOSE: Tetanus toxoid (Ttxd) encapsulated in polyester microspheres (MS) for single injection immunization have so far given pulsatile in vitro release and strong immune response in animals, but no boosting effect. This has been ascribed to insufficient toxoid stability within the MS exposed to in vivo conditions over a prolonged time period. This study examined the effect of co-encapsulated putative stabilizing additives. METHODS: Two different Ttxd were encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA 50:50) and poly(D,L-lactic acid) (PLA) MS by spray-drying. The influence of co-encapsulated additives on toxoid stability, loading in and release from the MS, was studied by fluorimetry and ELISA. RESULTS: Co-encapsulated albumin, trehalose and gamma-hydroxypropyl cyclodextrin all improved the toxoid encapsulation efficiency in PLGA 50:50 MS. Albumin increased the encapsulation efficiency of antigenic Ttxd by one to two orders of magnitude. Further, with albumin or a mixture of albumin and trehalose ELISA responsive Ttxd was released over 1-2 months following a pulsatile pattern. CONCLUSIONS: Optimized Ttxd containing MS may be valuable for a single-dose vaccine delivery system.

Capsules↗

Use of solid corrugated particles to enhance powder aerosol performance.

PURPOSE: To study the dispersion performance of non-porous corrugated particles, with a focus on the effect of particle surface morphology on aerosolization of bovine serum albumin (BSA) powders. METHODS: The solid-state characteristics of the spray-dried BSA powders, one consisting of smooth spherical particles and another corrugated particles, were characterized by laser diffraction, X-ray powder diffraction, scanning electron microscopy, confocal microscopy, thermogravimetric analysis, surface area analyzer, and buoyancy method. The powders were dispersed using the Rotahaler and the Dinkihaler coupled to a four-stage liquid impinger operating at 30 to 120 L/min. Fine particle fraction (FPF) was expressed as the wt. % of BSA particles of size < or =5 microm collected from the liquid impinger. RESULTS: Apart from the morphology and morphology-related properties (specific surface area, envelope density), the corrugated particles and spherical particles of BSA had very similar solid-state characteristics (particle size distribution, water content, true density, amorphous nature). Using the Dinkihaler, the FPFs of the corrugated particles were 10-20 wt. % higher than those of the smooth particles. Similar FPF differences were found for the powders dispersed by the Rotahaler, but the relative changes were larger. In addition, the differences were inversely proportional to the air flows (17.3% at 30 L/min, 25.2% at 60 L/min, 13.8% at 90, 8.5% at 120 L/min). Depending on the inhaler, capsule and device retention and impaction loss at the impinger throat were lower for the corrugated particles. CONCLUSIONS: Enhanced aerosol performance of powders can be obtained by surface modification of the particles. The surface asperities of the corrugated particles could lower the true area of contact between the particles, and thus reduce the powder cohesiveness. A distinct advantage of using corrugated particles is that the inhaler choice and air flow become less critical for these particles.

Administration, Inhalation↗

Infrared imaging of pharmaceutical materials undergoing compaction.

The goal of this study was to use infrared thermography as a new technique to investigate the heat released during compaction and consolidation of pharmaceutical powders and granules. Real-time temperature measurements without physical contact with tablets were provided by a highly sensitive (+/- 0.1 degrees C at 30 degrees C) infrared camera (Agema Infrared Systems, Model 470 with CM-SOFT software). High-resolution images were captured at the takeoff point, i.e., less than 1 sec after compaction, stored on floppy disks, and then analyzed on a regular PC equipped with a VGA color monitor. Thermal surface profiles of tablets were obtained with high geometric and temperature resolution. Reproducibility of the camera readouts was better than 3%. The model granulation used was a direct compression blend of microcrystalline cellulose, spray-dried lactose, and magnesium stearate. This blend was compressed using an instrumented Korsch PH106 rotary press fitted with 1 station of 19.1 x 7.9-mm (0.750 x 0.312-in.) capsule-shaped tools. The effects of compaction force (6-20 kN), rate (130- to 360-msec contact time), and lubricant level (0.5 and 1.0%) on postcompaction temperature rise, caused by heat released during compaction, were investigated. The presence and location of nonhomogeneous heat distribution were assessed as well. Results have shown that the heat released during compaction increases with compaction force. Tablet surface temperatures of 33.8 +/- 0.7 degrees C were observed at 20 kN compaction force in contrast to 29.5 +/- 0.3 degrees C at 6.7 kN.(ABSTRACT TRUNCATED AT 250 WORDS)

Infrared Rays↗

The influence of sodium glycocholate and other additives on the in vivo transfection of plasmid DNA in the lungs.

PURPOSE: A plasmid containing the luciferase 'marker' cDNA was constructed to test non viral gene delivery formulations in vivo. METHODS: A scale up procedure was devised to produce up to gram quantities of plasmid. Sufficient quantities were generated to process and test the DNA with various additives and to generate a spray-dried powder formulation of the plasmid. Male Sprague-Dawley rats (250 g) were intratracheally instilled with 200-250 microl of solution containing 200 microg plasmid +/- lipid [DC Chol:DOPE 1:1 molar (2mg/kg)] growth factors [KGF (10 mg/kg), EGF (5 mg/kg)], permeation enhancers [sodium glycocholate (0.01 to 10% w/v)), sodium deoxycholate (1% w/v), beta-cyclodextrin (1% w/v)], surfactant [Tween 80 (1% w/v)], a mucolytic [N-acetylcysteine (10% w/v)] and positively charged synthetic polymers [PVAVAM 6 and 14%]. Animals were sacrificed 24 hr post-dose and the lungs were assayed for luciferase using a chemiluminescent assay. RESULTS: The relative ability of the materials to promote luciferase production in the lungs was permeation enhancer >> DNA alone > or = lipid, mucolytic, surfactant, growth factor > polymer. Protein production in the lungs ranged from 10 times below the DNA control (approximately 16 pg) using the polymers (approximately 1.5 pg) to approximately 125 times greater than the control using the permeation enhancer (approximately 2050 pg). The transfection capabilities of the majority of additives was low. The enhancing effects of sodium glycocholate were dose-dependent and perhaps associated with the critical micelle concentration. Although the bile salt was the most successful of the tested compounds, it resulted in significant mortality when used at concentrations greater than 1% w/v. CONCLUSIONS: The results suggest that transfection can be significantly enhanced by additives such as NaGC but some toxicity may be unavoidable.

Animals↗

Solid-state 13C nuclear magnetic resonance spectroscopic study on amorphous solid complexes of tolbutamide with 2-hydroxypropyl-alpha- and -beta-cyclodextrins.

PURPOSE: The objective of the study was to obtain structural information of inclusion complexes of tolbutamide with HP-alpha- and -beta-cyclodextrins in amorphous state. METHOD: The solid complexes of tolbutamide with HP-alpha- and -beta-CyDs in molar ratios of 1:1 and 1:2 (guest:host) were prepared by the spray-drying method, and their interactions were investigated by solid-state 13C nuclear magnetic resonance (NMR) spectroscopy. RESULTS: The solid 1:1 and 1:2 tolbutamide/HP-CyD complexes showed halo pattern on the powder X-ray diffractogram and no thermal change in DSC curves, indicating they are in an amorphous state. 13C NMR signals of the butyl moiety were broader than those of the phenyl moiety in the HP-alpha-CyD solid complex, whereas the phenyl moiety showed significantly broader signals than the butyl moiety in the HP-beta-CyD solid complex. As temperature increased, signals of the phenyl carbons became markedly sharper, whereas the butyl carbons only sharpen slightly in the HP-d-CyD complex. In contrast, signals of the butyl carbons became significantly sharper whereas those of phenyl carbons only slightly changed in the HP-beta-CyD complex. CONCLUSIONS: Solid state 13C NMR spectroscopic studies indicated that the butyl moiety of tolbutamide is predominantly included in the HP-alpha-CyD cavity, whereas the phenyl moiety in the HP-beta-CyD cavity in amorphous complexes.

2-Hydroxypropyl-beta-cyclodextrin↗

On technological and immunological benefits of multivalent single-injection microsphere vaccines.

PURPOSE: With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity. METHODS: Mono- and multivalent vaccines of Haemophilus influenzae type b (Hib) conjugate, diphtheria toxoid (DT), tetanus toxoid (TT), and pertussis toxin (PT) in poly (lactic acid) and poly(lactic-coglycolic acid) microspheres were prepared by spray drying, and the influence of coencapsulated antigens and excipients on antigen loading, release, and stability was examined. Two tetravalent formulations were tested in guinea pigs. RESULTS: Monovalent Hib and PT vaccines showed loading efficiencies of 10% (Hib) and 30% (PT) in both polymers. The loading efficiencies increased upon addition of trehalose and, even more, when the antigens were coencapsulated in di- and trivalent combinations. Highest loading efficiencies (> 80%) were achieved with trivalent formulations (DT + PT + Hib) that also contained coencapsulated albumin. The percentage of antigen released during 24 h of incubation was typically 10-40% and decreased as loading efficiency increased. Enzyme-linked immunosorbent assay (ELISA) data revealed that TT, DT, and PT remained antigenic throughout the encapsulation and subsequent release processes. Finally, all antigens maintained their immunogenicity, since strong and sustained antibody responses were elicited after a single injection of tetravalent microsphere vaccines (DT + TT + PT + Hib) in guinea pigs. CONCLUSIONS: This study reveals technologic benefit as well as an immunological potential of multivalent single-injection microsphere vaccines. The results support our hypothesis that coencapsulation of several antigens may intrinsically improve entrapment of antigenic and immunogenic antigen probably by virtue of increased protein concentration during microencapsulation leading to mutual stabilization of the components.

Animals↗

Dissolution rate enhancement by in situ micronization of poorly water-soluble drugs.

PURPOSE: The purpose of this study was to evaluate a novel in situ micronization method avoiding any milling techniques to produce nano- or microsized drug particles by controlled crystallization to enhance the dissolution rate of poorly water-soluble drugs. METHODS: Ibuprofen, itraconazole, and ketoconazole microcrystals were prepared by the association of the previously molecularly dispersed drug using a rapid solvent change process. The drug was precipitated in the presence of stabilizing agents, such as hydrocolloids. The obtained dispersion was spray-dried. Particle size, morphology, dissolution rate, specific surface area, and wettability were analyzed. Physicochemical properties were characterized using differential scanning calorimetry and X-ray diffractometry. RESULTS: The obtained dispersions showed a homogeneous particle size distribution. Drugs are obtained in a mean particle size of approximately 2 microm and below. A high specific surface area was created and in situ stabilized. Different stabilizers showed differences in protecting the precipitated drug from crystal growth. The surface was hydrophilized because of the adsorbed stabilizer. Thus, a drug powder with markedly enhanced dissolution rate was obtained. CONCLUSIONS: In situ micronization is a suitable method for the production of micro-sized drugs. This technique can be performed continuously or discontinuously and uses only common technical equipment. Compared to milled products drug properties are optimized as all particle surfaces are naturally grown, the particle size is more uniformly distributed and the powder is less cohesive.

Chemical Precipitation↗

Hollow filler-binders as excipients for direct compaction.

PURPOSE: As an effect of their plastic deformation behavior, ductile materials create a large surface for bonding during compaction. However, a serious drawback is their high lubricant sensitivity, preventing the formation of strong bonds. The purpose of this study was both an increase in compactibility and a reduction of the lubricant sensitivity of ductile filler-binders by using hollow particles. This was illustrated for inulin. METHODS: Both solid and hollow inulin particles were prepared by spray-drying. Unlubricated tablets and tablets containing 0.5% magnesium stearate were compressed in a compaction simulator, operating at 300 mm/s. The tablet crushing strength was determined with a Schleuniger apparatus. RESULTS: The compaction of unlubricated, solid inulin particles showed that the product had good compatibility. This was caused by plastic deformation of the ductile, amorphous material under load, creating a large surface for bonding. After lubrication, however, the bonding properties decreased significantly, which was caused by the presence of a lubricant film. Hollow inulin particles have an increased compactibility as compared with solid particles and a strongly reduced lubricant sensitivity. Scanning electron micrographs show that hollow particles fragment before they start plastic deformation. This fragmentation behavior is supported by tablet surface area measurements and calculation of the buckling strength. This effect was responsible for both a higher crushing strength and a lower lubricant sensitivity as compared with solid inulin particles. CONCLUSIONS: Compactibility of inulin particles can be increased, and lubricant sensitivity can be decreased by using hollow instead of solid particles.

Drug Compounding↗

Factors influencing the compressive strength of an injectable calcium sulfate-hydroxyapatite cement.

A biphasic injectable bone substitute, suitable for filling bone defects, that sets in the body, based on calcium sulfate and hydroxyapatite (HA), is presented. For applications in bone defects the compressive strength is important to assure support of the defect site during loading when the patient is weight bearing. To control the strength, the influence of four different factors; the liquid-to-powder (L/P) ratio, the HA particle morphology, the HA content and the amount of accelerator, were investigated. alpha-Calcium sulfate hemihydrate (CSH) and four different HA powders (three sintered and one spray-dried) were used. All differed in size and morphology. CSH and each HA powder were mixed together with distilled water to form the bone substitute. An accelerator, in form of calcium sulfate dihydrate, was added to the powder phase to obtain an adequate setting time. Cylindrical specimens were compression tested. A lower L/P-ratio gave stronger cement, but was more difficult to inject. The shape and the morphology of the HA particles influenced the strength, and reducing the amount of HA increased the strength. The amount of accelerator (calcium sulfate dihydrate) had no influence.

Journal Article↗

Preparation of the red yeast, Xanthophyllomyces dendrorhous, as feed additive with increased availability of astaxanthin.

Xanthophyllomyces dendrorhous (Phaffia rhodozyma) is used as a colorant for aquaculture, egg yolks, and crustaceans but its carotenoids can only be absorbed by animals when its cell wall is degraded. Conditions that degraded the cell wall of X. dendrorhous were developed. To measure the degrees of cell wall degradation, the carotenoid extractability (extracted carotenoid by acetone/total carotenoid) unit was used. Treatment with HCl (0.2 M, 9 h, 90 degrees C) followed by neutralization to pH 3 by NaOH and spray-drying increased carotenoid extractability to 100% with minimal decomposition.

Basidiomycota↗

Development of tissue scaffolds using selective laser sintering of polyvinyl alcohol/hydroxyapatite biocomposite for craniofacial and joint defects.

The growing interest in scaffold-guided tissue engineering (TE) to guide and support cell proliferation in the repair and replacement of craniofacial and joint defects gave rise to the quest for a precise technique to create such scaffolds. Conventional manual-based fabrication techniques have several limitations such as the lack of reproducibility and precision. Rapid prototyping (RP) has been identified as a promising technique capable of building complex objects with pre-defined macro- and microstructures. The research focussed on the viability of using the selective laser sintering (SLS) RP technique for creating TE scaffolds. A biocomposite blend comprising of polyvinyl alcohol (PVA) and hydroxyapatite (HA) was used in SLS to study the feasibility of the blend to develop scaffolds. The biocomposite blends obtained via spray-drying technique and physical blending were subjected to laser-sintering to produce test specimens. The SLS-fabricated test specimens were characterized using scanning electron microscopy and X-ray diffraction. The test specimens were also tested for bioactivity by immersing the samples in simulated body fluid environment. The results obtained ascertained that SLS-fabricated scaffolds have good potential for TE applications.

Biocompatible Materials↗

A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark.

The purpose of this cohort study is to shed further light on the potential carcinogenic effect indicated by a Swedish case control study of the 2,4-dichlorophenol and 4-chloro-ortho-cresol based phenoxy herbicides, unlikely to be contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). In the present study it was the intention to include all persons employed in manufacture of phenoxy herbicides in Denmark before 1982. The predominant product was MCPA and only a very limited amount of 2,4,5-T was processed in one of the two factories included in the study. Registration of the cohort was based on company records, supplemented with data from a public pension scheme from 1964 onwards. Ninety-nine percent of registered employees could be followed up. Cancer cases were identified by linkage with the National Cancer Register. Totals of 3,390 males and 1,069 females were included in the study. In the analysis special attention was given to soft tissue sarcomas (STS) and malignant lymphomas (ML) which are the diagnostic groups indicated to be associated with exposure to phenoxy herbicides in the Swedish studies. Five cases of STS were observed among male employees in contrast to 1.84 expected cases. This result supports the Swedish observation of an increased risk of STS following exposure to phenoxy herbicides unlikely to be contaminated with 2,3,7,8-TCDD. However, several potential biases have to be taken into account in interpretation of this observation and these are discussed. Seven cases of ML were observed among male employees in contrast to 5.37 expected which does not support the Swedish observation of an excess risk. The total cancer risk among persons employed in manufacture and packaging of phenoxy herbicides was equivalent to the cancer risk in the Danish population. Among males thus employed 11 lung cancer cases were observed in contrast to 5.33 expected. Attention should be given to exposure to spray dried MCPA-sodium salt in the plants, but other work place exposures and tobacco consumption may have contributed to the increased risk. The tabulation of data by many diagnostic groups may explain the excesses observed for rectum cancer among males and cervical cancer among females. The study has revealed that several potential biases have to be taken into account when the Swedish observations are tested in other settings.

Chemical Industry↗

Soy molasses as fermentation substrate for production of butanol using Clostridium beijerinckii BA101.

Spray-dried soy molasses (SDSM) contains the sugars dextrose, sucrose, fructose, pinitol, raffinose, verbascose, melibiose, and stachyose. Of the 746 g kg(-1) total sugars in SDSM, 434 g kg(-1) is fermentable using Clostridium beijerinckii BA101. SDSM was used to produce acetone, butanol, and ethanol (ABE) by C. beijerinckii BA101 in batch cultures. Using 80 g l(-1) SDSM, 10.7 g l(-1) ABE was produced in P2 medium. Higher concentrations of SDSM resulted in poor solvent production due to the presence of excessive salt and inhibitory components. C. beijerinckii BA101 in SDSM at 80 g l(-1) concentration produced 22.8 g l(-1) ABE when supplemented with 25.3 g l(-1) glucose. SDSM contains 57.4 g kg(-1) mineral ash and 2% tri-calcium phosphate. Tri-calcium phosphate up to 43.1 g l(-1) was not inhibitory and at a tri-calcium phosphate concentration of 28.8 g l(-1), the culture produced more solvents (30.1 g l(-1)) than the control experiment (23.8 g l(-1)). In contrast, sodium chloride was a strong inhibitor of C. beijerinckii BA101 cell growth. At a concentration of 10 g l(-1) sodium chloride, a maximum cell concentration of 0.6 g l(-1) was achieved compared to 1.7 g l(-1) in the control experiment. The effects of two salts on specific growth rate constant (mu) and specific rate of ABE production (nu) for C. beijerinckii BA101 were examined.

Acetone↗