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PubMed1982

Effect on particle size on the compaction mechanism and tensile strength of tablets.

The effect of particle size variation on tablet tensile strength for spray-dried lactose, Sta-Rx 1500 and Avicel PH-101 was investigated. Decreasing the particle size of spray-dried lactose and Sta-Rx 1500 resulted in stronger compacts whereas the tablet tensile strength of Avicel PH-101 was unaffected by particle size variation. The Heckel relationship, at two different contact times, was used to examine the predominant compaction mechanism. This was independent of the size fractions studied for all three materials. Angle of repose and Hausner ratio measurements indicated a correlation between the internal forces of friction and cohesion of the sized powders and the tensile strength of compacts formed from them.

Hardness↗
PubMed2006

Reduced use of antibiotic growth promoters in diets fed to weanling pigs: dietary tools, part 1.

Antibiotics improve health and productive performance of pigs. There is increasing evidence that other dietary ingredients may provide similar, but probably not identical, benefits. A properly prepared immune egg product, spray-dried plasma, or a high level of dietary zinc can provide protection against enteric infection in young pigs. Spray-dried plasma also increases growth rate dramatically, and zinc increases it substantially. The evidence in refereed publications also indicates that organic acids increase growth rate substantially, but does not clearly identify the most effective acid or combination of acids. Whey proteins, lactose, mannan oligosaccharide, or a high level of dietary copper provides a modest but useful increase in growth rate. It is not clear whether conventional egg products or other milk proteins may be beneficial. There are many other feed ingredients commercially available that may improve health and productive performance of pigs.

Animal Feed↗
PubMedDate not supplied

Cellulose acetate trimellitate ethylcellulose blends for non-steroidal anti-inflammatory drug (NSAID) microspheres.

Ketoprofen (Ket), a non-steroidal anti-inflammatory drug, has been incorporated into polymeric micromatrices (microspheres) prepared by a spray drying process and made of cellulose acetate trimellitate (CAT)/ethylcellulose (EC) blends. Drug loaded microspheres were obtained by spray-drying organic solutions of the two polymers and the drug. Characterization of the microparticles (morphology, particle size distribution, drug content, yield of production, surface properties, solvent residues) was carried out and in-vitro release behaviour measured. The release rate of the drug diminished as the proportion of EC was raised.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Polymorphic behavior of sprayed lipid micropellets and its evaluation by differential scanning calorimetry and scanning electron microscopy.

Considering the importance of polymorphism occurring in solid dosage forms causing instability, the polymorphic behavior of spray-dried and -congealed lipid micropellets was examined by differential scanning calorimetry and scanning electron microscopy. The results showed that both of the spraying processes exert an important effect on their polymorphic and crystallization properties. In spray-drying, due to the rapid solvent evaporation, the obtained lipid micropellets possess an unstable polymorphic form. This unstable form transforms gradually toward a stable form by storage at elevated temperatures. The same modifications were observed with spray-congealed lipid micropellets. The type of glyceride (composition, chain length), solvent and drugs (estradiol cypionate, medroxyprogesterone acetate) and, further, the presence of a stabilizing agent such as lecithin affect the polymorphic transition and its rate.

Calorimetry, Differential Scanning↗
PubMed1999

Optimization of a dry powder inhaler formulation of nacystelyn, a new mucoactive agent.

The aim of this study was to optimize a dry powder inhaler formulation containing a new mucoactive drug, nacystelyn. Formulations were made using three types of lactose, crystalline alpha-lactose, spray-dried lactose and a roller-dried anhydrous beta-lactose. The roller-dried anhydrous beta-lactose possessed the most adequate surface properties, resulting in a significantly higher (P < 0.05) in-vitro lung deposition of nacystelyn than the conventional crystalline alpha-lactose and spray-dried lactose. The particle size distribution of roller-dried beta-lactose was optimized also. Within the size ranges tested (63-100, 90-125 and 100-160 microm), the coarser the lactose, the higher the in-vitro deposition of the drug (up to 40%). In contrast, the in-vitro lung deposition of 100-160 microm roller-dried beta-lactose was very low (< 0.5%), so limiting the potential risk of lung irritation due to the carrier. The influence of the ratio of active ingredient/excipient (w/w) was also investigated. No difference was observed for mixtures from 1:2 to 1:4 while higher dilutions (1:5 and 1:6) showed significantly (P < 0.005) lower deposition results. Finally, the influence of the airflow rate was assessed. No dependence of the fine particle dose was observed between 40 and 80 L min(-1) while significantly higher results were obtained at 100 L min(-1). The dry powder inhaler formulation of nacystelyn using the unusual roller-dried anhydrous beta-lactose resulted in very high and reproducible in-vitro deposition results. However, the latter needs to be confirmed by in-vivo studies.

Acetylcysteine↗
PubMed1995

Influence of dietary beta-glucan on growth performance, nonspecific immunity, and resistance to Streptococcus suis infection in weanling pigs.

Three experiments, using 344 pigs, were conducted to evaluate the influence of beta-glucan on growth performance, neutrophil and macrophage function, haptoglobin production, and resistance to Streptococcus suis challenge in weanling pigs. In Exp. 1, 144 pigs were used to evaluate the influence of .1% dietary beta-glucan in a soybean meal- or milk protein-based diet on growth performance and neutrophil function. Pigs fed beta-glucan from d 7 to 14 after weaning had lower ADFI (P < .01) and, although not significant, ADG was lower for pigs fed beta-glucan than for pigs fed control diets. However, no differences were observed in growth performance or neutrophil function for pigs fed control or diets containing beta-glucan from d 7 to 35 after weaning. Experiment 2 was a 28-d growth assay in which pigs were fed a diet with or without .1% beta-glucan, containing 7.5% spray-dried plasma protein and 25% dried whey from d 0 to 14 after weaning. Pigs then were fed corn-soybean mealbased diets containing 2.5% spray-dried blood meal and 10% dried whey. No differences in growth performance were observed. Experiment 3 was a 35-d assay to evaluate growth performance, neutrophil and macrophage function, and plasma haptoglobin concentration. Pigs were challenged on d 28 postweaning with intravenous S. suis. In Exp. 3, pigs were fed diets without or with .025 or .05% beta-glucan. Dietary beta-glucan did not influence neutrophil or macrophage function. However, pigs fed diets containing .025% beta-glucan had increased (P < .05) ADG and ADFI and were heavier (P < .05) on d 28 after weaning than pigs fed the control diet. No differences in feed efficiency (G/F) were detected between treatments. Pigs fed beta-glucan had decreased (P < .10) plasma haptoglobin on d 14, 21, and 28 after weaning. However, Fisher's Exact test revealed that more (P < .04) pigs fed a diet containing .025% beta-glucan died by d 12 after challenge with S. suis. In conclusion, these data suggest the existence of a complex interaction involving growth performance and resistance to S. suis in pigs fed .025% beta-glucan.

Aging↗
PubMed1999

Formulation and physical characterization of large porous particles for inhalation.

PURPOSE: Relatively large (>5 microm) and porous (mass density <0.4 g/cm3) particles present advantages for the delivery of drugs to the lungs, e.g., excellent aerosolization properties. The aim of this study was, first, to formulate such particles with excipients that are either FDA-approved for inhalation or endogenous to the lungs; and second, to compare the aerodynamic size and performance of the particles with theoretical estimates based on bulk powder measurements. METHODS: Dry powders were made of water-soluble excipients (e.g., lactose, albumin) combined with water-insoluble material (e.g., lung surfactant), using a standard single-step spray-drying process. Aerosolization properties were assessed with a Spinhaler device in vitro in both an Andersen cascade impactor and an Aerosizer. RESULTS: By properly choosing excipient concentration and varying the spray drying parameters, a high degree of control was achieved over the physical properties of the dry powders. Mean geometric diameters ranged between 3 and 15 microm, and tap densities between 0.04 and 0.6 g/cm3. Theoretical estimates of mass mean aerodynamic diameter (MMAD) were rationalized and calculated in terms of geometric particle diameters and bulk tap densities. Experimental values of MMAD obtained from the Aerosizer most closely approximated the theoretical estimates, as compared to those obtained from the Andersen cascade impactor. Particles possessing high porosity and large size, with theoretical estimates of MMAD between 1-3 microm, exhibited emitted doses as high as 96% and respirable fractions ranging up to 49% or 92%, depending on measurement technique. CONCLUSIONS: Dry powders engineered as large and light particles, and prepared with combinations of GRAS (generally recognized as safe) excipients, may be broadly applicable to inhalation therapy.

Administration, Inhalation↗
PubMed1983

Storage of milk powders under adverse conditions. 2. Influence on the content of water-soluble vitamins.

Storage of milk powder under unfavourable conditions accelerates the normally slow deterioration in nutritional quality. The effects of such storage on the water-soluble vitamin composition were examined. (a) Spray-dried whole milk containing 25 g water/kg was stored at 60 degrees and 70 degrees and sampled weekly to 9 weeks. (b) Spray-dried whole milk and skimmed milk were adjusted to contain 40 and 100 g water/kg and stored at 37 degrees in nitrogen and in oxygen. Samples were taken for analysis at intervals during storage. The samples were analysed for eight B-complex vitamins and ascorbic acid, and also for total lysine, 'reactive lysine' and 'lysine as lactulosyl-lysine'. Storage at 60 degrees caused rapid destruction of folic acid (53% loss at 4 weeks) and slower loss of thiamin, vitamin B6 and pantothenic acid (18% at 8 weeks). There was no change in the content of riboflavin, biotin, nicotinic acid and vitamin B12. At 70 degrees the rate of destruction of the four labile vitamins was much increased; 18% or less survived at 4 weeks. At 37 degrees and 40 g water/kg there was little change in total and 'reactive' lysine during storage for 57 d. Lactulosyl-lysine was demonstrably present but at low concentration. There was considerable loss of folate (72%) and ascorbate (91%) during storage for 30 d in O2, but no significant loss in N2. Thiamin fell by approximately 12% in 57 d, equally in O2 and N2. The content of the remaining vitamins was unchanged. At 100 g water/kg there were progressive Maillard changes. During 27 d in N2 the colour changed from cream to pale brown, but in O2 there was no perceptible colour change. Total lysine fell by 20% in 27 d, and 'reactive lysine' by 30%. Folate was stable during 16 d in N2, but largely (94%) destroyed in O2. Ascorbic acid was also destroyed in N2 as in O2. Thiamin fell by 41% in 27 d, equally in O2 and N2. Vitamin B6 was more labile, especially in N2, falling by 71% in 16 d. With skimmed-milk powder containing 100 g water/kg, storage at 37 degrees in O2 and N2 gave much the same results as for the corresponding whole-milk powder. The presence of milk fat had no marked effect on the stability of the water-soluble vitamins. Destruction of vitamins was clearly linked to the progress of Maillard-type reactions and was strongly influenced by time and temperature of storage, moisture content and, in some instances, by the presence of O2.

Animals↗
PubMed1999

Diphtheria and tetanus toxoid microencapsulation into conventional and end-group alkylated PLA/PLGAs.

The feasibility of biodegradable polyester microspheres (MS) for single injection vaccines will greatly depend on the toxoid stability within the MS exposed to in vivo conditions. This study examined the effects of polymer type and co-encapsulated additives on diphtheria (Dtxd) and tetanus (Ttxd) toxoid entrapment and stability. The co-encapsulated stabilizers influenced significantly the entrapment of Dtxd and Ttxd in PLA/PLGA MS. Typically, 5% BSA or trehalose decreased the amount of Dtxd entrapped in spray-dried MS, whereas BSA increased the entrapment in coacervated MS. Further, the entrapment of Dtxd decreased as a function of polymer hydrophobicity in spray-dried MS. Without additives, approx. 64, 43 and 16% entrapment efficiency of ELISA-reactive antigen was obtained for 14-17 kDa PLGA 50:50, PLGA 75:25 and PLA, respectively. The novel end-group stearylated 1-PLAs were only processed by coacervation. Satisfactory entrapment of 30-60% Dtxd was obtained. Here, albumin was a prerequisite for toxoid encapsulation, as BSA-free formulations produced strong toxoid precipitation. Furthermore, protein burst release increased with the more hydrophobic polymers, with Dtxd, Ttxd and the co-encapsulated BSA following a similar pattern and magnitude. This investigation also revealed that the method of protein extraction from the microspheres (O/W-partition or polymer hydrolysis) as well as the analytical methods (HPLC or ELISA) strongly influenced the determined amount of encapsulated toxoid and BSA. In conclusion, the study revealed the complexity of antigen microencapsulation when using different preparation and analytical techniques, as well as different types of materials.

Alkylation↗
PubMed2001

Microencapsulating properties of sodium caseinate.

Emulsions were prepared with 5% (w/v) solutions of sodium caseinate (Na Cas) and soy oil at oil/protein ratios of 0.25-3.0 by homogenization at 10--50 MPa. Emulsions were spray-dried to yield powders with 20--75% oil (w/w). Emulsion oil droplet size and interfacial protein load were determined. Microencapsulation efficiency (ME), redispersion properties, and structure of the powders were analyzed. The size of emulsion oil droplets decreased with increasing homogenization pressure but was not influenced by oil/protein ratio. Emulsion protein load values were highest at low oil/protein ratios. ME of the dried emulsions was not affected by homogenization pressure but decreased from 89.2 to 18.8% when the oil/protein ratio was increased from 0.25 to 3.0, respectively. Mean particle sizes of reconstituted dried emulsions were greater than those of the original emulsions, particularly at high oil/protein ratios (>1.0), suggesting destabilization of high-oil emulsions during the spray-drying process.

Caseins↗
PubMed2003

Development of a novel granular detergent with an interspersion particle comprising an anionic surfactant and a polymeric polycarboxalate.

This paper discusses a process for making a novel granular detergent with an interspersion particle comprising an anionic surfactant and a polymeric polycarboxalate. This process contains three steps to develop the interspersion particles with anionic surfactant and polymeric ploycarboxalate. The first step was to form a detergent particle by spray drying of an aqueous detergent slurry comprising anionic surfactant (liner alkyl benzene sulfonate) with the different levels of polymeric polycarboxalate. In the second step, the spray-dried granules were densified and ground by a roll compacter and a grinder. The ground particles were coated by nonionic and zeolite in a vertical batch type high shear mixer (third step). In this study, the feasibility to make better performance of granular detergent was discussed.

Alkanesulfonic Acids↗
PubMed2002

A study of the crystallisation of amorphous salbutamol sulphate using water vapour sorption and near infrared spectroscopy.

The crystallisation of amorphous salbutamol sulphate prepared by spray drying was monitored using a humidity controlled microbalance (Dynamic Vapour Sorption apparatus, Surface Measurement Systems) combined with a near-infrared probe. Amorphous salbutamol sulphate was prepared by spray drying from a solution in water. The particles were then analysed using scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, isothermal microcalorimetry and water vapour sorption analysis combined with near-infrared spectroscopy (NIR). Isothermal microcalorimetry and water vapour sorption combined with NIR spectroscopy were able to detect the transition from the amorphous to crystalline state. However while the isothermal microcalorimeter showed only a classic crystallisation exotherm when the material was exposed at 75% RH, the DVS-NIR results at the same humidity highlighted a more complex process. When exposed at 75% RH, the uptake of water was followed by crystallisation that was detected using NIR. The expulsion of water after crystallisation was very slow and at a constant rate whether the material was exposed to 75 or 0% RH. The NIR and DVS studies indicated that the material had crystallised very soon after exposure to high RH. The water that was expelled during crystallisation was not displaced from the particles and remained associated with the particles for many days. This study showed that the use of gravimetric analysis together with NIR spectroscopy provided valuable information on the dynamics of the crystallisation of salbutamol sulphate. The retention of water within recently crystallised salbutamol is potentially important to the behaviour of dosage forms containing the amorphous (or partially amorphous) form of this drug.

Albuterol↗
PubMed1980

Micromeritic properties of sulfamethoxazole microcapsules prepared by gelatin-acacia coacervation.

Micronized sulfamethoxazole particles were microencapsulated using the gelatin-acacia complex conacervation method. The effects of the coacervation pH and the amount of formaldehyde used on the micromeritic parameters of the microcapsules were investigated. The particle-size and the wall thickness distributions were log-normal forms. As the pH was increased, the particle size decreased (8.5-28.5 micrometers). The porosity of various pH-adjusted microcapsules was between 0.158 and 0.277. The particle size of formalized microcapsules was larger than that of the unformalized microcapsules because formalization prevents shrinking of microcapsules during the dehydration and drying process. A smooth surface appeared on the unformalized microcapsule, but a net-like wrinkled structure was observed upon scanning the formalized one. Moreover, folding and invaginating structures were found on the spray-dried microcapsules. The optimum coacervation pH value was 3.5, at which the highest core content was obtained (77.5% w/w). Approximately 6.73 microgram of formaldehyde remained in 1 g of the microcapsules formalized with 50 ml of formaldehyde. The crystalline sulfamethoxazole in the microcapsules prepared by spray drying the coacervate slurries was changed into the amorphous form, while the microcapsules dried in the conventional manner showed the same sulfamethoxazole form as the starting substance.

Acacia↗
PubMed2006

Preparation and characterization of chitosan/gelatin microcapsules containing triclosan.

Chitosan/gelatin (C/G) microcapsules containing triclosan were prepared by a spray drying method. The core material, triclosan (TS) dissolved in octyl salicylate (OS), were emulsified in an aqueous solution containing variable ratios of chitosan/gelatin. The microcapsules were obtained by spray-drying the emulsions. On the scanning electron micrographs, the microcapsules were spherical and exhibited a core and shell morphology. The thermograms of the microcapsules showed no evidence for the melting of TS, suggesting that TS remained dissolved in the cores of the microcapsules and did not exist as a solid crystalline even after dry microcapsules were formed. According to the results of microelectrophoresis study, the point of zero charge of the microcapsules occurred around pH 9.0 and a higher content of chitosan in the microcapsule wall resulted in a higher positive charge of zeta potential. The degree of release of TS and OS from the C/G microcapsules in an aqueous solution of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated. When chitosan is included in the wall of microcapsules, the degree of release was suppressed. This indicates that chitosan forms a more compact wall than gelatin. On the other hand, TS was released much more than OS. The preferred release of TS is probably due to the higher solubility of TS in the HP-beta-CD solution.

Calorimetry, Differential Scanning↗
PubMed2004

Importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in PLA/PLGA microspheres.

The aim of the work was to develop biodegradable microspheres for controlled delivery of the somatostatin analogue vapreotide and maintenance of sustained plasma levels over 2-4 weeks after a single injection in rats. Vapreotide was microencapsulated into end-group capped and uncapped low molecular weight poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) by spray-drying and coacervation. Microspheres were prepared from single and blended (1:1) polymer types. The microparticles were characterized for peptide loading, in vitro release and pharmocokinetics in rats. Spray-drying and coacervation produced microspheres in the size range of 1-15 and 10-70 microm, respectively, and with encapsulation efficiencies varying between 46% and 87%. In vitro release of vapreotide followed a regular pattern and lasted more than 4 weeks, time at which 40-80% of the total dose were released. Microspheres made of 14-kDa end-group uncapped PLGA50:50 or 1:1 blends of this polymer with 35 kDa end-group uncapped PLGA50:50 gave the best release profiles and yielded the most sustained plasma levels above a pre-defined 1 ng/ml over approximately 14 days. In vitro/in vivo correlation analyses showed for several microsphere formulations a linear correlation between the mean residence time in vivo and the mean dissolution time (r=0.958) and also between the amount released between 6 h and 14 days and the AUC(6h-14d) (r=0.932). For several other parameters or time periods, no in vitro/in vivo correlation was found. This study demonstrates that controlled release of the vapreotide is possible in vivo for a duration of a least 2 weeks when administered i.m. to rats. These results constitute a step forward towards a twice-a-month or once-a-month microsphere-formulation for the treatment of acromegaly and neuroendocrine tumors.

Animals↗
PubMed2005

Gentamicin-loaded discs and microspheres and their modifications: characterization and in vitro release.

Osteomyelitis is an infection of the bone, and successful treatment involves local administration for about 6 weeks. Gentamicin is a very hydrophilic drug and tends to come out into the water phase when microspheres are fabricated using solvent evaporation method. Hence, spray drying is an option, and it was observed that the release rate tends to be fast when the particle size is small and large particles cannot be prepared by spray drying. In an effort to get better encapsulation efficiency and release rate, we have worked on the possibility of compressing the microspheres into discs and modifying the porosity of the discs by using biocompatible materials like polyethylene glycol (PEG) and calcium phosphates and also on the fabrication of double-walled and composite microspheres. In the case of microspheres, two methods of fabrication both based on solvent evaporation method were employed. The two polymers used are poly-L-lactide (PLLA) and copolymers of poly-DL-lactic-co-glycolic acid (PLGA). One method is based on the spreading coefficient theory for the formation of double-walled microspheres by using single solvent, while the other is based on the property of PLLA not being soluble in ethyl acetate (EA). Characterization to check if the microspheres formed are double-walled was performed. The fabrication method where two solvents, dichloromethane (DCM) and ethyl acetate, were used gave double-walled microspheres, while the other where only dichloromethane was used gave composites. The double-walled microspheres were smaller in size compared to the composites, which were in the range of 100-600 microm. This can be attributed to the difference in the fabrication procedure. We were able to achieve better encapsulation efficiencies of more than 50% and slower release rates, which lasted for about 15 days. It was observed that size played a major role in the encapsulation efficiency and release rates. The possibility of achieving better results by studying the effect of concentration of polymer in solvent and the effect of using different polymers was investigated.

Anti-Bacterial Agents↗
PubMed2003

Rheological study on mucoadhesivity of some nasal powder formulations.

Various powder mixtures were used to administer insulin via the nasal route: a co-spray dried mixture of Amioca starch and Carbopol 974 P (1/3), drum dried waxy maize starch and Carbopol 974 P (9/1), maltodextrin DE38/Carbopol 974 P (9/1) and pure drum dried waxy maize starch. Oscillatory rheology is performed to study and compare the viscosity, elasticity and mucoadhesivity of these powder formulations. There was no rheological synergism detectable with the co-spray dried mixture of Amioca starch and Carbopol 974 P (1/3), drum dried waxy maize starch and Carbopol 974 P (9/1) and maltodextrin DE38/Carbopol 974 P (9/1). Interaction due to entanglements was seen with drum dried waxy maize starch (100%). The differences in nasal bioavailability between the different carriers could be explained by differences in G' (storage modulus, elasticity) and G" (loss modulus, viscosity) values. The formulation giving the highest bioavailability, provided also the highest G' and G" values.

Adhesives↗
PubMed2003

Microcalorimetric measurement of the interactions between water vapor and amorphous pharmaceutical solids.

PURPOSE: Use a microcalorimetric technique to measure the interactions between water vapor and amorphous pharmaceutical solids and describe the relationship between long-term physical stability and the storage relative humidity (RH) at constant temperature. METHODS: A thermal activity monitor was used to characterize interactions of water vapor with spray-dried amorphous sucrose, lactose, raffinose, and sodium indomethacin. Differential scanning calorimetry was used to measure glass transition temperature, Tg. X-ray powder diffraction was used to confirm that the spray-dried samples were amorphous. Scanning electron microscopy was used to examine particle morphology. Specific surface area was determined by BET analysis of nitrogen and krypton adsorption isotherms. RESULTS: The moisture-induced thermal activity traces (MITATs) of the materials in this study exhibit general behavior that helps explain the effect of moisture content on the physical stability of the glassy phase at a given storage temperature. At some RH threshold, RHm, the MITAT exhibits a dramatic increase in the energy of interaction between water vapor and the glass that cannot be explained by a phase or morphology change. Calorimetric data indicate that water vapor-solid interactions are reversible below RHm; above RHm, energetic hysteresis is observed and water-water interactions predominate. In addition, the MITAT was deconvoluted into sorptive and nonsorptive components, making it possible to assign the observed heat flow to unique thermal events. Samples stored at a RH just below RHm for more than 2 months show no evidence of morphology or phase change. In addition, the MITAT can be deconvoluted into sorptive and nonsorptive components by using a twin-calorimeter arrangement. This analysis provides specificity to the microcalorimetric analysis and helps explain the nature of the physical changes that occur during the hydration glassy phase. CONCLUSIONS: The MITAT is a useful tool to determine the onset of moisture-induced physical instability of glassy pharmaceuticals and may find a broad application to determine appropriate storage conditions to ensure long-term physical stability.

Calorimetry↗