Relative bioavailability of phosphorus in high-protein sunflower meal for broiler chickens and effects of dietary phytase supplementation on bone traits, growth performance, and apparent ileal digestibility of nutrients.

An experiment was conducted to determine the relative bioavailability (RBV) of P in high-protein sunflower meal (HP-SFM) fed to broiler chickens based on bone traits and to determine the effects of dietary phytase supplementation and increasing levels of HP-SFM as a P source on bone traits, growth performance, and apparent ileal digestibility (AID) of DM and nutrients. In total, 240 broiler chicks were randomly allotted to 1 of 10 experimental diets with 6 replicate cages of 4 birds each and fed experimental diets from day 14 to 21 of age. Diets included a corn-soybean meal-based basal diet (0.35% total P; P-deficient diet), or the basal diet supplemented with 0.05, 0.10, or 0.15% P from either monosodium phosphate (MSP) or HP-SFM. Another 3 diets were formulated by supplementing the HP-SFM-containing diets with 500 phytase unit/kg of phytase. The bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) of femur and tibia and tibia ash content increased (linear, P < 0.01) with increasing dietary P content from MSP. A linear increase in femur and tibia BMC, femur BA, and tibia BMD was also observed (P < 0.01) with increasing level of dietary P from HP-SFM. The RBV of P in HP-SFM based on femur and tibia BMC were 41 and 44%, respectively. Dietary phytase supplementation increased (P < 0.01) most of bone traits of the birds except for femur BMD. In addition, birds fed the diets supplemented with dietary phytase had greater (P < 0.05) BW gain, feed efficiency, and AID of P than those fed the diets without dietary phytase. In conclusion, the estimated RBV of P in HP-SFM to P in MSP were 41 and 44% based on femur and tibia BMC, respectively. Also, dietary phytase supplementation increased AID of P, growth performance, and bone traits of the birds fed P-deficient diets containing increasing inclusion level of HP-SFM as a P source.

Improvement of the nutritional value of high-protein sunflower meal for broiler chickens using multi-enzyme mixtures.

Two experiments were conducted to determine the effect of replacing soybean meal (SBM) with a high-protein sunflower meal (HiSFM) without or with multi-enzyme mixtures on growth performance, nutrient utilization, jejunal digesta viscosity, and excreta moisture in broiler chickens. In experiment 1, 400 chicks were divided into 40 replicates of 10 birds and fed for 35 d a corn-soybean meal (CSBM) control diet or CSBM with 25 (HiSFM25), 50 (HiSFM50), 75 (HiSFM75), or 100% (HiSFM100) of total SBM replaced by HiSFM. During d 0 to 35, increasing HiSFM content in diets linearly reduced (P < 0.0001) BW, FI, and BW gain (BWG). Feeding HiSFM25 or HiSFM50 resulted in similar growth performance as CSBM (P > 0.05). In experiment 2, 120 chicks were divided into 24 replicates of 5 birds and fed CSBM or HiSFM75 diet without or with enzyme A (supplying 4,000, 500, and 8,000 U/kg of xylanase, alpha-amylase, and protease, respectively) or enzyme B (supplying 1,700, 1,100, 240, 30, 1,200, 360, 1,500, and 120 U/kg of cellulase, pectinase, mannanase, galactanase, xylanase, glucanase, amylase, and protease, respectively) for 21 days. Excreta moisture content was determined weekly, and birds were euthanized on d 22 to collect jejunal and ileal digesta for viscosity and apparent ileal digestibility (AID) measurements, respectively. Compared with CSBM, feeding HiSFM75 reduced (P < 0.05) BWG and G: F, enzymes A and D alleviated BWG and G: F reduction (P < 0.05), and enzyme A reduced (P = 0.037) the excreta moisture content, whereas the treatments did not influence AID or jejunal digesta viscosity measurements. In conclusion, experiment 1 results show that HiSFM can replace up to 50% of SBM without depressing growth performance in either the starter or finisher phase, whereas experiment 2 shows that enzymes A and B supplementation can alleviate the growth depression associated with feeding HiSFM75. These results suggest that enzyme supplementation can enhance HiSFM inclusion in broiler diets without affecting productivity or barn hygiene management.

Changing the omega-6 to omega-3 fatty acid ratio in sow diets alters serum, colostrum, and milk fatty acid profiles, but has minimal impact on reproductive performance.

This experiment tested the hypothesis that reducing the omega-6 (n-6) to omega-3 (n-3) fatty acid (FA) ratio in sow diets will improve performance, characterized by increased litter size, decreased preweaning mortality, and improved growth performance. Second, we determined if the FA profile in sow and piglet blood, colostrum, and milk are altered when sows are fed diets with varied n-6:n-3 ratios and if the dietary FA ratio impacts circulating concentrations of IgG, IgA, eicosapentaenoic (EPA), or docosahexaenoic (DHA) acid. Sows (n=150) were assigned to 1 of 5 treatments (each divided into gestation and lactation diets) on d 80 of gestation. Period 1 (P1) is defined as d 80 of gestation to weaning and Period 2 (P2) refers to the subsequent breeding to weaning. Diets were wheat and barley based (5% crude fat) and treatments consisted of a control (tallow), 3 diets with plant oil-based n-6:n-3 ratios (9:1P, 5:1P, and 1:1P), and a 5:1 fish oil diet (5:1F). Litter size was unaffected by treatment during P1 and P2 (P>0.10). In P1, birth weight was unaffected by diet (P>0.10); however, weaning weight (P=0.019) and ADG from birth to weaning (P=0.011) were greatest for piglets born to 9:1P and 5:1P sows. During P2, 5:1F sows consumed 10% less feed during lactation (P=0.036), tended to have reduced piglet birth weights (P=0.052), and piglet weaning weight was reduced by 0.8 kg (P=0.040) relative to the other diets. Colostrum and piglet serum IgA and IgG concentrations were unaffected by diet (P>0.10). Serum n-3 FA were greatest in sows (P<0.01) consuming 1:1P and 5:1F diets and in their offspring (P=0.014). Serum α-linolenic acid (ALA) was greatest in 1:1P sows and EPA and DHA were greatest in 5:1F sows (P<0.01). In pre-suckle piglet serum, ALA did not differ among treatment groups (P>0.10). Relative to piglets of sows consuming the control diet, EPA was 2.5-fold greater in the 1:1P group and 4-fold greater in 5:1F group (P<0.01) before suckling. In post-suckle samples, ALA was greatest in piglets from the 1:1P sows (P<0.01) and EPA and DHA were greatest in piglets from the 5:1F sows (P<0.01). Feeding diets with plant-based n-6:n-3 ratios of 5:1 or 1:1 did not impact performance relative to a control group but improved the conversion of ALA into EPA and increased the transfer of n-3 to piglets through milk. When a fish-based 5:1 ratio diet was fed, pre-weaning mortality was increased, and piglet birth and weaning weights decreased.

Farming system design for innovative crop-livestock integration in Europe.

The development of integrated crop-livestock systems (ICLS) is a major challenge for the ecological modernisation of agriculture but appears difficult to implement at a large scale. A participatory method for ICLS design has been developed and implemented in 15 case studies across Europe, representing a range of production systems, challenges, constraints and resources for innovation. Local stakeholders, primarily farmers, but also cooperatives, environmental-association representatives and natural-resource managers, were involved in the identification of challenges and existing initiatives of crop-livestock integration; in the design of new options at field, farm and territory levels; and then in qualitative multicriteria assessment of these options. A conceptual framework based on a conceptual model (crops, grasslands, animals) was developed to act as a boundary object in the design step and invite innovative thinking in 'metabolic' and 'ecosystemic' approaches. A diversity of crops and grasslands interacting with animals appeared central for designing sustainable farming systems at the territory level, providing and benefitting from ecosystem services. Within this diversity, we define three types of integrated systems according to their degrees of spatial and temporal coordination: complementarity, local synergy, territorial synergy. Moreover, the options for cooperation and collective organisation between farmers and other stakeholders in territories to organise and manage this diversity of land use revealed opportunities for smart social innovation. The qualitative multicriteria assessment identified farmer workload as the main issue of concern while demonstrating expected benefits of ICLS simultaneously for economic, agronomic, environmental and social criteria. This study concludes that participatory design of ICLS based on a generic multi-level and multi-domain framework and a methodology to deal with a local context can identify new systems to be tested. Further assessment and redesign work will be performed in later stages of the European FP7 CANTOGETHER project.

MELODIE: a whole-farm model to study the dynamics of nutrients in dairy and pig farms with crops.

In regions of intensive pig and dairy farming, nutrient losses to the environment at farm level are a source of concern for water and air quality. Dynamic models are useful tools to evaluate the effects of production strategies on nutrient flows and losses to the environment. This paper presents the development of a new whole-farm model upscaling dynamic models developed at the field or animal scale. The model, called MELODIE, is based on an original structure with interacting biotechnical and decisional modules. Indeed, it is supported by an ontology of production systems and the associated programming platform DIESE. The biotechnical module simulates the nutrient flows in the different animal, soil and crops and manure sub-models. The decision module relies on an annual optimization of cropping and spreading allocation plans, and on the flexible execution of activity plans for each simulated year. These plans are examined every day by an operational management sub-model and their application is context dependent. As a result, MELODIE dynamically simulates the flows of carbon, nitrogen, phosphorus, copper, zinc and water within the whole farm over the short and long-term considering both the farming system and its adaptation to climatic conditions. Therefore, it is possible to study both the spatial and temporal heterogeneity of the environmental risks, and to test changes of practices and innovative scenarios. This is illustrated with one example of simulation plan on dairy farms to interpret the Nitrogen farm-gate budget indicator. It shows that this indicator is able to reflect small differences in Nitrogen losses between different systems, but it can only be interpreted using a mobile average, not on a yearly basis. This example illustrates how MELODIE could be used to study the dynamic behaviour of the system and the dynamic of nutrient flows. Finally, MELODIE can also be used for comprehensive multi-criterion assessments, and it also constitutes a generic and evolving framework for virtual experimentation on animal farming systems.

Feed ingredients differing in fermentable fibre and indigestible protein content affect fermentation metabolites and faecal nitrogen excretion in growing pigs.

To study the fermentation characteristics of different non-conventional dietary fibre (DF) sources with varying levels of indigestible CP content and their effects on the production of fermentation metabolites and on faecal nitrogen (N) excretion, an experiment was conducted with 40 growing pigs (initial BW 23 kg) using wheat bran (WB), pea hulls (PH), pea inner fibres (PIF), sugar beet pulp (SBP) or corn distillers dried grains with solubles (DDGS). The diets also contained soya protein isolate, pea starch and sucrose, and were supplemented with vitamin-mineral premix. Faecal samples were collected for 3 consecutive days from day 10, fed with added indigestible marker (chromic oxide) for 3 days from day 13 and pigs were slaughtered on day 16 from the beginning of the experiment. Digesta from the ileum and colon were collected and analysed for short-chain fatty acids (SCFA) and ammonia (NH3) content. The apparent total tract N digestibility was the lowest (P < 0.001) in diets based on DDGS (74%), medium in diets with WB and SBP (76% each) and highest in those with PIF and PH (79% and 81%, respectively). Expressed per kg fermented non-starch polysaccharides (NSP), faecal N excretion was higher with DDGS and WB diets (130 and 113 g/kg NSP fermented, respectively) and lower with PIF, PH and SBP diets (42, 52 and 55 g/kg NSP fermented, respectively). The PH-based diets had the highest (P < 0.05) SCFA concentrations, both in the ileum and the colon (27 and 122 mMol/kg digesta, respectively). The highest NH3 concentration was also found in the colon of pigs fed with PH (132 mMol/kg digesta). Loading plot of principle component analysis revealed that the CP : NSP ratio was positively related with faecal N excretion and NH3 concentration in colon contents, whereas negatively related with SCFA concentration in colon contents. In conclusion, pea fibres and SBP increased SCFA and reduced NH3 concentration in the pig's intestine and reduced faecal N excretion, which makes pea fibres and SBP an interesting ingredient to use in pig diet to improve the positive effect of DF fermentation on the gastrointestinal tract and reduce faecal N excretion.

Barley and oat cultivars with diverse carbohydrate composition alter ileal and total tract nutrient digestibility and fermentation metabolites in weaned piglets.

An experiment was conducted to evaluate the effects of cereal carbohydrate form (isolated v. cereal matrix) and level, especially mixed-linked ß-glucan (hereafter referred to as ß-glucan) and starch amylase/amylopectin ratio on nutrient digestibility and fermentation parameters in the intestines of weaned pigs. Four hulless barley cultivars containing varying ß-glucan levels (41 to 84 g/kg) were compared with hulled barley, supplemented or not with a ß-glucan concentrate (BBG; 270 g/kg ß-glucan) and two oat cultivars for digestibility and fermentation metabolites. Seventy-two weaned piglets (BW = 12.8 ± 1.9 kg) were assigned to one of nine diets composed of 815 g/kg cereal, 60 g/kg whey, 90 g/kg soy protein isolate and 35 g/kg minerals. After 15 days, the pigs were killed, and digesta collected from ileum and colon were analyzed for proximate nutrients, short-chain fatty acids (SCFAs), lactic acid (LA) and ammonia. Ileal and total tract digestibility of proximate nutrients and non-starch polysaccharides (NSPs) were determined using HCl-insoluble ash as a marker. Organic matter (OM) ileal digestibility was greater (P < 0.05) for diets based on hulless barley (77% ± 1.1% on average), as compared with hulled barley (64% ± 1.4%) and oat (58% ± 1.5%). Similar trends were found for total tract OM digestibility, varying from 90% ± 0.3% for hulless barley to 67% ± 0.4% for oat, on average. NSP digestibility differed (P < 0.05) within and between cereal types, ranging from 20% (hulled barley plus 163 g/kg BBG or 40 g/kg ß-glucan) to 51% (SB94893 hulless barley cultivar with high ß-glucan and high amylose ratio) at the ileum and from 44% (hulled barley) to 84% (SB94893 cultivar) at the total tract level. No dietary effect (P > 0.05) was found for SCFA concentration in ileal contents, whereas in colonic contents, SCFA was lower in pigs fed oat (P < 0.001). LA concentration was greater (P < 0.001) in the colon of pigs fed hulless barley than in pigs fed hulled barley and oat. Expressed per kg carbohydrate (NSP + starch) fermented, the ammonia concentration at the colon was lowest for hulled barley diets (supplemented with ß-glucan) and the highest for oat diets. In conclusion, the interaction of both form and level of ß-glucan impacted nutrient digestibility and fermentation. Hulless barleys with high soluble NSP such as ß-glucan and resistant starch yielded, in general higher SCFA and LA and lower ammonia. Hulless barleys may, therefore, have potential for use in feeding strategies designed to improve gut health in pigs.

Nutritional value of flaxseed meal for swine and its effects on the fatty acid profile of the carcass.

Four experiments were conducted to determine the nutritional value of flaxseed meal [FSM; 133 g of ether extract (EE) and 343 g of CP/kg of DM] for swine. In Exp. 1, apparent fecal digestibility (AD) of DM and EE, and the DE and NE contents were determined in growing pigs (n = 32; initial BW, 70 +/- 3 kg) and gestating sows (n = 24; parities, 2 to 4). Diets contained 0, 100, 200, or 300 g of FSM/kg at the expense of wheat, barley, and soybean meal. Fecal samples were collected for 3 d after a 9-d adaptation. The AD for DM and EE were 72.0 +/- 0.4% and 67.4 +/- 4.7%, respectively, for growing pigs and 68.0 +/- 0.5% and 48.9 +/- 1.9% for sows. The DE content was 3.51 and 3.54 Mcal/kg for growing pigs and gestating sows, and NE was estimated to be 2.43 and 2.44 Mcal/kg for growing pigs and sows, respectively. Five ileally cannulated barrows (initial BW, 38 +/- 3 kg) were fed semi-synthetic diets containing 400 g of FSM/kg for a 7-d period (4-d adaptation and 3-d collection) then 7 d of N-free diet to determine basal endogenous N losses in Exp. 2. Standardized ileal digestible AA contents were 29.6 +/- 1.0, 5.7 +/- 0.3, 12.1 +/- 0.8, 16.8 +/- 1.0, 10.3 +/- 0.4, 5.3 +/- 0.3, 14.0 +/- 0.7, 9.4 +/- 0.5, 2.9 +/- 0.2, and 13.8 +/- 0.8 g/kg of dry FSM for Arg, His, Ile, Leu, Lys, Met, Phe, Thr, Trp, and Val, respectively. In Exp. 3, the AD of P and the effects of phytase inclusion on P availability were determined. Five groups of 8 barrows (initial BW, 45 +/- 4 kg) were fed a 300 g of FSM/kg semi-synthetic diet with increasing concentrations of exogenous phytase [0, 575, 1,185, 2,400 and 2,570 phytase units (FTU)/kg]. The AD of P increased from 21 to 61% (P < 0.001). Broken-line analysis estimated the optimal phytase inclusion rate to be 1,415 FTU/kg of diet. Growth performance and carcass fatty acid (FA) profiles of pigs fed FSM were determined in Exp. 4. Two hundred pigs (100 barrows and 100 gilts; initial BW, 32 +/- 4 kg), blocked by sex, were housed in groups of 5 pigs per pen and fed 1 of 4 diets containing 0, 50, 100, or 150 g of FSM/kg. Six market pigs per diet were selected for carcass FA analysis. The ADG, ADFI, and G:F were not affected by dietary FSM (P > 0.05). Increasing FSM in the diet from 0 to 150 g of FSM/kg increased the alpha-linolenic acid content from 11.1 +/- 0.2 to 47.4 +/- 1.2 mg/g of backfat (P < 0.001) and from 5.0 +/- 0.1 to 10.1 +/- 0.6 mg/g of loin tissue (P < 0.001). Flaxseed meal despite its deficiency in lysine can be included up to 150 g/kg of diets for swine and will contribute to the enrichment of the carcass with n-3 fatty acids.

Influence of source and concentrations of dietary fiber on in vivo nitrogen excretion pathways in pigs as reflected by in vitro fermentation and nitrogen incorporation by fecal bacteria.

The inclusion of dietary fiber (DF) in diets has been suggested as a way to reduce NH(3) emission in pig barns because it contributes to a shift in N excretion from urine to feces owing to enhanced bacterial growth in the intestines. This study compared an in vitro method to measure bacterial protein synthesis during fermentation with an in vivo N excretion shift induced by diets differing in DF concentrations and solubility. The first experiment measured the effect of graded concentrations of sugar beet pulp (SBP; 0, 10, 20, and 30%) in corn- and soybean meal-based diets on in vivo N excretion partitioning between the urine and feces. A second experiment investigated the replacement of SBP, rich in soluble DF, with oat hulls (OH), rich in insoluble DF (20:0, 10.5:10.5, and 0:22%, respectively). In parallel, the fermentation characteristics of the dietary carbohydrates not digested in the small intestine were evaluated in an in vitro gas test, based on their incubation with colonic microbiota, using a mineral buffer solution enriched with (15)N. The N originating from the buffer solution incorporated into the bacterial proteins (BNI) was measured when half the final gas volume was produced (8.5 to 14.5 h of fermentation) and after 72 h of fermentation. Short-chain fatty acids were determined in the liquid phase. In the first experiment, the inclusion of SBP linearly decreased urinary N excretion from 0.285 to 0.215 g of N excreted in the urine per gram of N ingested and decreased the urinary-N:fecal-N excretion ratio from 2.171 to 1.177 (P < 0.01). In the second experiment, substituting SBP with OH linearly increased the urinary-N:fecal-N excretion ratio (P = 0.009). Unlike short-chain fatty acid production, BNI was greater at half-time to asymptotic gas production than at 72 h of fermentation. Sugar beet pulp enhanced BNI linearly (P < 0.001), 2.01, 2.06, and 2.35 mg g(-1) of diet with 10, 20, and 30% SBP, respectively, as compared with 1.51 mg for the control diet. The substitution of SBP with OH decreased BNI (P < 0.01). With the exception of final gas production, all in vitro kinetic characteristics and BNI were correlated with in vivo N excretion parameters, and regression equations for the prediction of N excretion pathways from in vitro data were identified. Even if the presence of resistant starch in the diet might alter the composition of the fibrous residue that is fermented, the in vitro method is a possible useful tool for the formulation of diets, reducing the effects of pig production on the environment.

The source of fermentable carbohydrates influences the in vitro protein synthesis by colonic bacteria isolated from pigs.

Two in vitro experiments were carried out to quantify the incorporation of nitrogen (N) by pig colonic bacteria during the fermentation of dietary fibre, including non-starch polysaccharides and resistant starch. In the first experiment, five purified carbohydrates were used: starch (S), cellulose (C), inulin (I), pectin (P) and xylan (X). In the second experiment, three pepsin-pancreatin hydrolysed ingredients were investigated: potato, sugar-beet pulp and wheat bran. The substrates were incubated in an inoculum, prepared from fresh faeces of sows and a buffer solution providing 15N-labelled NH4Cl. Gas production was monitored. Bacterial N incorporation (BNI) was estimated by measuring the incorporation of 15N in the solid residue at half-time to asymptotic gas production (T/2). The remaining substrate was analysed for sugar content. Short-chain fatty acids (SCFA) were determined in the liquid phase. In the first experiment, the fermentation kinetics differed between the substrates. P, S and I showed higher rates of degradation (P < 0.001), while X and C showed a longer lag time and T/2. The sugar disappearance reached 0.91, 0.90, 0.81, 0.56 and 0.46, respectively, for P, I, S, C and X. Among them, S and I fixed more N per gram substrate (P < 0.05) than C, X and P (22.9 and 23.2 mg fixed N per gram fermented substrate v. 11.3, 12.3 and 9.8, respectively). Production of SCFA was the highest for the substrates with low N fixation: 562 and 565 mg/g fermented substrate for X and C v. 290 to 451 for P, I and S (P < 0.01). In the second experiment, potato and sugar-beet pulp fermented more rapidly than wheat bran (P < 0.001). Substrate disappearance at T/2 varied from 0.17 to 0.50. BNI were 18.3, 17.0 and 10.2 fixed N per gram fermented substrate, for sugar-beet pulp, potato and wheat bran, respectively, but were not statistically different. SCFA productions were the highest with wheat bran (913 mg/g fermented substrate) followed by sugar-beet pulp (641) and potato (556) (P < 0.05). The differences in N uptake by intestinal bacteria are linked to the partitioning of the substrate energy content between bacterial growth and SCFA production. This partitioning varies according to the rate of fermentation and the chemical composition of the substrate, as shown by the regression equation linking BNI to T/2 and SCFA (r2 = 0.91, P < 0.01) and the correlation between BNI and insoluble dietary fibre (r = -0.77, P < 0.05) when pectin was discarded from the database.

Influence of carrier on the performance of dry powder inhalers.

The aim of this work is to study carriers which can become alternatives to monohydrate lactose in dry powder inhalers and to consider particle parameters that influence adhesion between drug and carrier in dry powder inhalers. Different forms of mannitol, lactose and maltitol were mixed with either terbutaline sulphate or formoterol fumarate. The blends were submitted to different adhesion tests where drug detachment from the carrier was obtained either through mechanical vibration or by aspiration. Parameters like particle shape, roughness, amorphous content and cristalline form may affect interactions between drug and carrier. In our case, crystallized forms of the carrier offered lower adhesion but better release of the active ingredient than spray-dried forms. The crystallized mannitol produced maximal fine particle dose. The blends of the mannitols and the two active ingredients gave different results. The two techniques used to assess the adhesion of drugs to carrier particles provide complementary information about drug/carrier interactions and detachment. The mechanical sieving allows to assess blend stability and the air-jet sieving makes it possible to determine how easily the drug separates from carrier. For the drugs tested, the results of fine particle doses are in agreement with the Alpine air-jet sieve results. The tests used are helpful for the choice of a new carrier in the field of the development of new carriers for dry powder inhalers.

Aerosolization potential of cyclodextrins--influence of the operating conditions.

The aim of this work is to characterize the aerosols obtained by jet nebulization with cyclodextrin solutions and to study the influence of operating conditions on nebulization efficiency. Two cyclodextrins, an hydroxypropyl cyclodextrin (Kleptose HP) and a polydisperse methyl beta cyclodextrin (Crysmeb), were tested with 14 nebulizers that differ geometrically. We first determined the physicochemical properties of density, viscosity, and surface tension for the cyclodextrin solutions. Nebulization efficiency was evaluated by measuring droplet size, nebulization rate, quantity of solution nebulized, and nebulization time. We studied the influence of the technological parameters of pressure and nebulizer type and the influence of the formulation on performance efficiency. The use of different nebulizers and different pressure conditions results in variable efficiency. Regardless of the type of nebulizer, an increase in pressure decreases droplet size and increases nebulization rate. The influence of the nebulizer design is considerable. The aqueous cyclodextrin solutions studied can generate aerosols in particle size ranges suitable for pulmonary deposition. Large quantities of aerosol can be nebulized in acceptable nebulization times. The cyclodextrin concentration does not modify nebulization efficiency in the range tested.

Influence of granulation and compaction on the particle size of ibuprofen--development of a size analysis method.

The aim of this work was to study the impact of the process on drug particle size. We chose ibuprofen, practically insoluble in water, as granulometry greatly influences its dissolution rate. We developed an original method using a laser granulometer to assess the size of ibuprofen within a blend before and after granulation and then compression. Wet granulation was performed with a Lodige and a Diosna granulator. The granules were then compressed. The evolution of ibuprofen particle size after these operations was checked. Two grades of ibuprofen differing in size were studied: ibuprofen 25 and ibuprofen 50. After the wet granulation of ibuprofen 50 with a Lodige or a Diosna granulator, a decrease in size was observed. This could be caused by shocks occurring in the granulator. On the other hand, after compression of the granules, ibuprofen particle size increased and was greater than that measured before granulation. Compression could induce some fragmentation of ibuprofen associated with the plastic deformation and then, under pressure, a closeness of the fragments or deformed particles which could bind or associate with one another because the melting point of ibuprofen is not very high. In the case of ibuprofen 25, the same phenomena were observed after compression. But, after granulation, particle size was not modified. There was little breaking of ibuprofen particles in the granulator because they are much smaller than those of ibuprofen 50. This work shows the impact of the process on drug particle size when producing tablets. The method developed made it possible to differentiate and measure the size of ibuprofen particles in a blend.

Controlled drug release from Gelucire-based matrix pellets: experiment and theory.

The aim of this work was to elucidate the underlying drug release mechanisms from lipidic matrix pellets, using theophylline and Gelucire 50/02 as model drug and carrier material, respectively. Pellets were prepared by two different techniques: melt-solidification and extrusion-spheronization. The effects of different formulations and processing parameters on the resulting drug release kinetics in 0.1N HCl and phosphate buffer pH 7.4 were studied and the obtained results analyzed using adequate mathematical models in order to get further insight into the underlying mass transport mechanisms. The type of preparation technique was found to strongly affect the underlying drug release mechanisms. Drug release from pellets prepared by the melt-solidification method was primarily controlled by pure diffusion, whereas drug release from pellets prepared by the extrusion-spheronization method was purely diffusion-controlled only at early time points. After approximately 2h, the pellets started to disintegrate, resulting in decreased diffusion pathway lengths and, thus, increased drug release rates. Furthermore, the curing conditions significantly affected the theophylline release kinetics, whereas varying the initial drug loading from 20 to 50% (w/w) resulted only in a slight increase in the relative drug release rate. Interestingly, the effects of the size of pellets prepared by the melt-solidification method on the resulting drug release kinetics could be quantitatively predicted using an analytical solution of Fick's second law of diffusion. These predictions could be verified by independent experiments.

A survey of pig production systems in the rain forest of the Pacific coast Colombia.

A questionnaire-based survey was conducted in small-scale pig farms in the rain forest of the Colombian Pacific coast in order to study aspects of reproduction, nutrition and productivity. A total of 124 farmers was interviewed. They owned, on average, 13.6 pigs, including 2.3 sows, mainly of the Zungo breed. Pigs are reared in extensive systems and are allowed to wander freely in search of food. The sows produce, on average, 9.6 piglets/litter but, owing to poor sanitary conditions, 1.5 are born dead and only 6.3 are weaned alive. Two-thirds of the sows have five litters or more and the boars are also kept for a long time. This leads to high consanguinity rates within the herd and low productivity. Diets are based on maize, banana, tubers (taro, cassava) and fruits (peach palm, among others), and are rich in energy but poor in protein and minerals. The lack of protein and mineral sources appears to be the main limiting factor of these extensive production systems. Tree forages could partially solve the problem but are used by only 2% of the farmers. It is concluded that decreasing inbreeding, better piglet management and provision of balanced diets are areas that require immediate improvement.

Influence of the morphogranulometry and hydrophobicity of talc on its antisticking power in the production of tablets.

Antisticking power varies according to the talc considered. It is difficult to define the physical properties of talc implicated in its antisticking power. In this work, different talcs were characterized and an evaluation made of their performance in reducing sticking in tablet manufacturing. Determination of the specific surface area was made by permeametry, morphogranulometric analysis by laser diffractometry using a method, which made it possible to assess the mean thickness of talc particles, and measurement of water absorption kinetics was taken to assess hydrophobicity. The relationship between the characteristics of talcs and their antisticking power was then considered. There is a correlation between the particle size of talc and surface hydrophobicity. The detaching force of tablets appears to be dependent on the basal dimension of talc.

Cyclodextrins as a potential carrier in drug nebulization.

The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the feasibility of using different cyclodextrins (CDs) to elaborate pharmaceutical formulations for the inhalation route and tested the short-term toxicity of such formulations administered by inhalation to C57BL/6 mice. We have shown that HP-beta-CD, gamma-CD, as well as RAMEB aqueous solutions can undergo aerosolization and that the resulting droplet-size ranges are compatible with pulmonary deposition. In vivo, we have demonstrated that short-term exposure to inhaled HP-beta-CD, gamma-CD and RAMEB solutions are non-toxic after assessing bronchoalveolar lavage (BAL), lung and kidney histology, bronchial responsiveness to methacholine and blood urea. The only change noted is a slight increase in lymphocyte count in the BAL after HP-beta-CD and gamma-CD inhalation. We conclude that CDs are useful in significantly enhancing the solubility of apolar drugs with a view to inhalation therapy although an increase in lymphocyte counts in the BAL after CDs inhalations needs further investigations.

Development of 400 microm pellets by extrusion-spheronization: application with Gelucire 50/02 to produce a "sprinkle" form.

The aim of this study was to develop monodimensional, spherical particles of 400 microm by extrusion-spheronization. An Alexanderwerk GA65 cylinder extruder with two counter-rotating rollers associated with a Caleva model 15 spheronizer were used. The study was made with an auxiliary substance of fatty consistency and with amphiphilic properties: Gelucire 50/02. The plasticity of the mass can be deduced using a piston extruder. Pellet quality can be determined by particle-size analysis and shape estimation by microscopy. Modifications to the cylinders and the extruder itself are required for feasibility studies of extruded materials of 400 microm. The horizontal plate of the spheronizer had to be adapted to take into account the small size of the extruded materials. For the chosen auxiliary substance, Gelucire 50/02, the formulation of the wet mass to be extruded and the conditions required to obtain this mass were defined. The results show the feasibility of 400 microm pellets with Gelucire 50/02. At least 90% of the pellets have a particle size of between 250 microm and 500 microm and particle shape is acceptable. In this form the dose can be adapted to individual patients. After proving the feasibility of 400 microm spheroids of Gelucire 50/02, the association of a drug with it was considered.

Relation between structural characteristics of talc and its properties as an antisticking agent in the production of tablets.

Antisticking power varies according to the talc considered. Besides its chemical properties, it is necessary to assess its physical properties related to functionality. It is difficult to define the physical properties of talc implicated in its antisticking power. In this work, different talcs were characterised and their performance in reducing sticking in tablet manufacturing was evaluated. The following parameters were studied: apparent density, morphogranulometry, roughness, and the specific surface through the adsorption-desorption of argon. Next, the relationship between the characteristics of talcs and their antisticking power was considered. Talc before and after delamination-which is a way to obtain talcs with different physical characteristics-was compared. Antisticking power appeared to be dependent on the basal dimensions of talc, and on the ratio value of the external specific surface measured by diffractometry to the total specific surface by the BET method. Models to express the effect of textural factors of talc particles on antisticking power were defined.

Developing a study method for producing 400 microm spheroids.

The aim of this work was to obtain 400 microm spheroids that can be sprinkled on food to improve patient compliance particularly in the case of children and old people. A methodology to select wet masses for extrusion-spheronization through a 400 microm orifice was developed. The first step was to define the parameters that make it possible to assess the qualities required by the wet mass and the extrudates and evaluation norms: plasticity, cohesiveness, brittleness of the mass and the extrudates, and appearance of extrudates. A feasibility assay was then performed on the cylinder extruder, showing that extrusion of the lactose/Avicel PH 101/water (50/50/60) mass is not feasible through the 400 microm orifice. Precirol ato 5 and Gelucire 50/02 wetted with a sodium lauryl sulfate solution at 0.5% show plastic flow through the 400 microm diameter orifice. The presence of Avicel PH 101 does not improve plasticity for this orifice. Micropellets of 400 microm have been proved feasible as long as excipients with suitable pharmaceutical technological properties are used. After proving the feasibility of 400 microm spheroids of Gelucire 50/02, we considered the association of a drug with it.