Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Spray drying”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources
PubMed2006

Optimization of formulation components and characterization of large respirable powders containing high therapeutic payload.

The aim of the study was to optimize and characterize high therapeutic payload large respirable powders prepared by spray-drying technique for maximum fine particle fraction with minimum quantities of excipients. Influence of formulation components was optimized by a three-factor, five-level central composite design having different proportions of L-leucine (X1), tobramycin sulfate (X2), and poloxamer-188 (X3) as the independent variables and fine particle fraction as a response variable (Y). Large respirable powders were characterized for particle size, size distribution, moisture, crystallinity, and morphology. In vitro aerosol performance of powders was determined by an eight-stage Andersen cascade impactor using the Rotahaler. Mathematical model elucidated for Y was Y = 56.2068 + 5.7481 X1 - 3.0531 X2 + 0.8468 X3 + 1.1737 X1 X2 - 0.5012 X1 X3 - 0.7412 X2 X3 - 0.7149 X1(2) - 1.9212 X2(2) - 1.6187X3(2). The component of greatest influence on product performance (response variable) was found to be L-leucine. Lack of fit was not significant (p = 0.08), and regression equation predicted response for Y was in reasonably good agreement with experimental values (p = 0.01; R2 = 0.92). The optimal model predicted with a fine particle fraction of 62.8 +/- 2.6% with X1, X2, X3 levels of 20, 45.71, and 5.51 respectively. Large respirable powders with TB load of 45.7% w/w were prepared; they had smooth surface texture, dimpled spherical shape, roundness value close to 1(1.048 +/- 0.032) and were found to possess bulk tap densities of 0.04 g/cc, geometric particle sizes of 6-7 micro m, and emitted dose of 92%. The results of the studies suggest that in vitro aerosol performance was affected significantly by small and deliberate change of specific formulation components and its proportions. It may be concluded that appropriate type and proportion of excipients is necessary to obtain maximum fine particle fraction of large respirable powders containing high therapeutic payloads.

Adjuvants, Pharmaceutic↗
PubMed1981

[Nutritional physiology studies in pigs on the evaluation of modified proteins. 1. Results of the estimation of N-turnover, apparent and true digestibility of proteins in addition to apparent and true absorption of amino acids in the entire digestive tract].

Sulfuric acid-casein (A), spray dried isolated Vicia faba protein (B), Vicia faba protein/casein (1 : 1) protein fibres-untreated (C), treated with dialdehyde starch (D) or aluminum chloride (E) and meal of Vicia faba (F) were studied as sole protein sources in semisynthetic feed mixtures on 13 female pigs (40 to 45 kg body weight). Total utilization of nitrogen (b-value, PNu) and intermediate utilization (BW) were highest in A, followed by C. Protein C was superior to D. Protein E showed a drastic drop in protein quality compared with D because of a high decrease in S-containing amino acids content, however, their efficiency (bc-1-value) was not limited. Despite of a higher apparent digestibility by approximately 17 units in protein B, proteins B and F showed a similar quality. The true absorption of cystine (estimated by the balance of digestive tract) was corresponding to the protein quality of the respective step of treatment of protein C and was used for the correction of the gross content is S-containing amino acids.

Amino Acids↗
PubMed2000

Bioavailability of itraconazole in rats and rabbits after administration of tablets containing solid dispersion particles.

A tablet dosage form containing solid dispersions of itraconazole (Asd tablets) was prepared by using the spray-drying and wet granulation methods. The dissolution rate of itraconazole from Asd tablets was fast, with more than 90% released within 10 min, compared to less than 20% for a marketed product, Sporanox capsules. The oral absorption of itraconazole from Asd tablets was determined in rats and rabbits and was compared with that for Sporanox capsules. In the rat, there was no difference between the Asd tablets and Sporanox capsules in the mean area under the curve (AUC) (3089.5 +/- 4332.8 ng.hr/ml and 3653.9 +/- 2348.9 ng.hr/ml, respectively) and Cmax (295.0 +/- 344.5 and 390.5 +/- 169.4 ng/ml, respectively). Also, in the rabbit, no difference was found between the two products in the mean AUC (AUMC; 19357.9 +/- 5117.5 ng.hr/ml and 23382.2 +/- 6236.5 ng.hr/ml, respectively) and Cmax (766.4 +/- 276.5 and 1127.5 +/- 577.9 ng/ml, respectively). Despite the rapid in vitro release characteristics of itraconazole from the Asd tablets, the in vivo absorption of itraconazole was comparable to that of Sporanox capsules, with no difference in Tmax in both animal species. Serum levels of the major active metabolite hydroxyitraconazole were also measured. Itraconazole was rapidly converted to hydroxyitraconazole in both rats and rabbits, but there were species-specific differences in their pharmacokinetics. It is concluded that, in addition to drug solubility and dissolution characteristics, other formulation factors such as the physical state of the drug and the granulation process, may also need to be considered in the prediction of the in vivo absorption of itraconazole based on in vitro data.

Animals↗
PubMed2000

Study of omeprazole-gamma-cyclodextrin complexation in the solid state.

The possibility of obtaining inclusion complexes between omeprazole (OME) and gamma-cyclodextrin (gamma-CD) by kneading, spray-drying, coprecipitation, and freeze-drying was evaluated. All these methods lead to the isolation of a true inclusion compound, as evidenced by differential scanning calorimetry (DSC), infrared spectroscopy, and X-ray diffractometry on powder (PXRD). Moreover, PXRD and scanning electron microscopy (SEM) afforded data concerning crystallinity and surface characteristics of the solid phases obtained. In all cases, a significant increase of the release rate with respect to the drug alone was found, and it was attributed to the formation of an inclusion compound. Among the solid phases obtained, the comprecipitated product presented the highest dissolution rate.

Anti-Ulcer Agents↗
PubMed2000

The effect of particle morphology on the physical stability of pharmaceutical powder mixtures: the effect of surface roughness of the carrier on the stability of ordered mixtures.

The effect of particle morphology of the components on the physical stability of ordered mixtures was determined for a model system comprised of a mixture of micronized aspirin and a monodisperse carrier. Spray-dried lactose, crystallized lactose, microcrystalline cellulose, and dextrate were used as carriers. The surface texture of the carriers was quantified in terms of the ratio of the perimeter of the particles to that of an idealized shape at a constant magnification. Mixtures containing highly textured carriers segregated to a lesser extent than those containing smoother textured carriers. This was postulated to be due to the presence of a higher concentration of surface asperities on the coarse carriers that can constitute potentially strong adhesion sites for the fine component because of their higher energy relative to adjacent areas on the surface. The effect of the addition of a ternary component, magnesium stearate, on the stability of the above mixtures was studied. The observed differences in the segregation response were attributed to electrostatic charge effects.

Chemistry, Pharmaceutical↗
PubMed2000

Sustained-release butorphanol microparticles.

Various butorphanol-loaded microparticles have been prepared with a biodegradable copolymer P(FAD-SA) of erucic acid dimer (FAD) and sebacic acid (SA) and a copolymer P(CPP-SA) of carboxyphenoxypropane (CPP) and SA using a melt compounding and milling method. Drug release was measured in vitro following incubation of drug-loaded microparticles in water for injection at 37 degrees C. It was found that butorphanol was released in a sustained manner, yielding a cumulative drug release of about 100% over a period of 48 hr. Also, drug release was affected by drug loading and the size of the microparticles; however, it was not significantly influenced by the copolymer composition. Scanning electron microscopic (SEM) results showed that most of the particles were irregular in shape with uneven surfaces. The molecular weights of the copolymers were not changed after this fabrication process. In addition, 20% butorphanol-encapsulated microspheres were prepared with copolymer P(FAD-SA) by spray-drying. The SEM micrograph shows that the particle sizes of the microspheres ranged from 2 to 10 microns, and the external surfaces appear smooth. Moreover, rapid drug release was observed for these microspheres, with more than 92% of the encapsulated drug released within the first 2 hr.

Analgesics, Opioid↗
PubMed2001

Chitosan-alginate microparticles as a protein carrier.

The oral administration of peptidic drugs requires their protection from degradation in the gastric environment and the improvement of their absorption in the intestinal tract. For these requirements, a microsystem based on cross-linked alginate as the carrier of bovine serum albumin (BSA), used as a model protein, was proposed. A spray-drying technique was applied to BSA/sodium alginate solutions to obtain spherical particles having a mean diameter less than 10 microm. The microparticles were hardened using first a solution of calcium chloride and then a solution of chitosan (CS) to obtain stable microsystems. The cross-linking process was carried out at different CS concentrations and pH values of the cross-linking medium. The CS concentration affected the BSA loading in the microparticles prepared at a pH value less than the protein isoelectric point (pI). Moreover, the BSA loading at a pH value less than the pI was higher than that at a pH similar to the pI regardless of the CS concentration. This finding could be attributable to the formation of a BSA/alginate complex. The evaluation of the interaction between BSA and alginate at different pH values by means rheological measurements confirmed this hypothesis. This approach may represent a promising way to devise a microcarrier system with appropriate size for targeting the Peyer's patches, with appropriate immobilization capacity, and suitable for the oral administration of peptidic drugs.

Alginates↗
PubMed2001

Hydrogels formed by cross-linked polyvinylalcohol as colon-specific drug delivery systems.

Polyvinivlalcohol (PVA, of different molecular weights was cross-linked with succinyl, adipoyl, or sebacoyl chloride to obtain hydrogel-forming polymers and to determine their suitability as colon-specific drug delivery systems. Diclofenac sodium, propranolol hydrochloride, and vitamin B6 hydrochloride were used as hydrophilic model drugs with colon-specific release that should yield high concentrations in the large intestine, minimizing release in the upper part of the gastrointestinal tract. Spray -dried mixtures of the drugs and the polymer (at a 1:2 w/w ratio) were prepared, and the release of the drugs from the mixtures was evaluated in vitro at pH 2.0, 5.5, and 7.4. The results indicated the ability of the cross-linked polymers to slow the release of the drugs analyzed with respect to the pure drug dissolution at each pH. The lengthening of the cross-linker acyl chain was noted to decrease drug release further.

Algorithms↗
PubMed2002

Polydisperse powder mixtures: effect of particle size and shape on mixture stability.

The effect of the shape and size of the components on the stability of mixtures was evaluated in binary mixtures of drug and carrier. Aspirin was used as model drug; spray-dried lactose and microcrystalline cellulose were used as carriers. The coefficient of variation (CV) of the drug in the mixture at various time intervals during mixing was used as a measure of homogeneity. The stability of mixtures was assessed under conditions that were conducive to segregation-in this case, prolonged mixing. The pattern of change in CV with time was analyzed in terms of convective, shear, and diffusive mixing stages. The variation resulting from a change in the shape of the carriers was smaller than that resulting from size differences. The segregation rate constant, calculated on the assumption of a first-order mixing process, was found to be larger in mixtures having components of different shape than in mixtures having components of similar shape. In mixtures of micronized drug and carrier, the pattern of change in the CV of drug with mixing time was attributed to the distribution of agglomerates of micronized drug during convective mixing, followed by shearing of agglomerates and, finally, the distribution of the primary particles during diffusive mixing. Mixtures of non-cohesive powders of similar size and shape behaved like random mixtures of non-interacting components.

Aspirin↗
PubMed2002

Lonidamine solid dispersions: in vitro and in vivo evaluation.

Solid dispersions of lonidamine in PEG 4000 and PVP K 29/32 were prepared by the spray-drying method. Then, the binary systems were studied and characterized using differential scanning calorimetry, hot stage microscopy, and x-ray diffractometry. In vitro dissolution studies of the solid dispersed powders were performed to verify if any lonidamine dissolution rate or water solubility improvement occurred. In vivo tests were carried out on the solid dispersions and on the cyclodextrin inclusion complexes to verify if this lonidamine water solubility increase was really able to improve the in vivo drug plasma levels. Drug water solubility was increased by the solid dispersion formation, and the extent of increase depended on the polymer content of the powder. The greater increase of solubility corresponded to the highest content of polymer. Both the solid dispersions and the cyclodextrin complexes were able to improve the in vivo bioavailability of the lonidamine when administered per os. Particularly, the AUC of the drug plasma levels was increased from 1.5 to 1.9-fold depending on the type of carrier.

Animals↗
PubMed2003

Improvement of the low-temperature stability of an aqueous colloidal ethylcellulose dispersion, Aquacoat ECD, and preparation/characterization of a redispersible Aquacoat ECD powder.

Aquacoat ECD, an aqueous ethylcellulose dispersion, is susceptible to low-temperature storage, resulting in irreversible coagulation as indicated by a strong increase in viscosity and particle size. This destabilization of the ethylcellulose dispersion is caused by the anionic surfactant sodium dodecyl sulfate, which precipitates at low temperatures because of its low Krafft point. This problem could be solved by using the more hydrophilic, ethoxylated, sodium dodecyl ether sulfate, which was an effective stabilizer at low temperatures. A redispersible ethylcellulose powder was prepared by freeze- or spray-drying of the original polymer dispersion (Aquacoat ECD). The pH of the dispersion medium had a strong influence on the redispersibility of the dried ethylcellulose particles because of the dissociation behavior. At a pH > 7, polymer dispersions in the colloidal size range were obtained. At lower pH values, the dried ethylcellulose agglomerates could not be redispersed. Drug release studies from pellets coated with the redispersed and the original dispersion showed a comparable release pattern when using alkalized aqueous dispersion systems. Higher plasticizer concentration and curing of the coated pellets improved the film formation of the redispersed polymer particles.

Cellulose↗
PubMed2004

Design and atomization properties for an inside-out type effervescent atomizer.

Atomization of aqueous polymer solutions is a key step in the formulation of several pharmaceutical products. Droplet size control is essential in order to produce pharmaceutical products with the desired properties. The purpose of this paper is to investigate design issues for an inside-out type of effervescent atomizer used to spray water and aqueous solutions of polyvinylpyrrolidone (Kollidon K-30) and hydroxypropyl methylcellulose (Pharmacoat 603). The atomizer was operated at air-to-liquid mass ratios of 0.1, 0.3, and 0.5 and a feed pressure of 1172 kPa. Fluid viscosities ranged from 1 to 47 mPa.s. The influence of several atomizer design features was considered, including exit orifice length-to-diameter ratio, exit orifice diameter, the total area of the air injection holes, the distance between the air injection point and the exit orifice, the diameter of the mixing chamber, and the orientation of both air and liquid flows. Droplet size distributions were shown to vary significantly with the atomizer's exit orifice diameter, air injector design, and air injector distance to the exit orifice. In all cases air-to-liquid mass ratio played a key role in the mean droplet size. The design of the atomizer was shown to have the most pronounced effect on the mean droplet size at the lowest air-to-liquid mass ratios. Optimization of the atomizer design is very important in order to obtain small droplet sizes in pharmaceutical processes where the amount of air/gas should be minimized, e.g., closed-cycle spray drying and agglomeration processes.

Chemical Phenomena↗
PubMed2004

Mucoadhesive delivery systems. I. Evaluation of mucoadhesive polymers for buccal tablet formulation.

Different types of mucoadhesive polymers, intended for buccal tablet formulation, were investigated for their comparative mucoadhesive force, swelling behavior, residence time and surface pH. The selected polymers were carbopols (CP934, and CP940), polycarbophil (PC), sodium carboxymethyl cellulose (SCMC) and pectin representing the anionic type, while chitosan (Ch) as cationic polymer and hydroxypropylmethyl cellulose (HPMC) as a non-ionic polymer. Results revealed that polyacrylic acid derivatives (PAA) showed the highest bioadhesion force, prolonged residence time and high surface acidity. SCMC and chitosan ensured promising bioadhesive characteristics, whilst HPMC and pectin exhibited weaker bioadhesion. Different polymer combinations as well as formulations were evaluated to improve the mucoadhesive performance of the tablets. Bioadhesive tablet formulations containing either 5% CP934, 65% HPMC and 30% spray-dried lactose or 2% PC, 68% HPMC and 30% mannitol showed optimum mucoadhesion and suitable residence time. SCMC, when formulated individually, exhibited promising bioadhesion, acceptable swelling, convenient residence time and surface pH. In-vivo trials of these formulations proved non-irritative and prolonged residence of the mucoadhesive tablets on human buccal mucosa for 8 to 13 h.

Adhesiveness↗
PubMed2004

Multicomponent complexes of piroxicam with cyclodextrins and hydroxypropyl methylcellulose.

The purpose of the study was to investigate the effect of hydroxypropyl methylcellulose (HPMC) on the complexation of piroxicam (PX) with beta-cyclodextrin (beta-CD) and dimethyl-beta-cyclodextrin (DM-beta-CD) in solution and in the solid state. Phase solubility study revealed a positive effect of the polymer on the drug complexation. Improvement in stability constants values, Ks, of ternary complexes clearly proves the benefit of the HPMC addition for promoting higher complexation efficiency. Solid binary and ternary complexes were prepared by spray drying. Drug-CD and drug-CD-polymer interactions were studied in the solid state by differential scanning calorimetry (DSC), zeta-potential measurements, and particle size distribution. A marked increase in the PX dissolution rate was observed even in binary and ternary complexes. The presence of HPMC in ternary complexes slightly retarded the release of PX. Cyclodextrin complexation increased the PX concentration gradient over the semipermeable membrane, resulting in an increased PX flux. The retarded diffusion of PX to the membrane interface decreased the PX flux values of the ternary complexes.

Biological Availability↗
PubMed2001

Effect of carrier excipient and processing on stability of indorenate hydrochloride/excipient mixtures.

The purpose of this investigation was to determine the solid-state chemical stability of a model drug, indorenate hydrochloride, as a function of carrier excipient and mixing process. Physical mixtures and granules were prepared by tumble mixing and alcoholic granulation with and without binder. Stability of the mixtures was estimated using differential scanning calorimetry and isothermal degradation studies at 40, 50, and 60 degrees C. Average first-order degradation constants at 25 degrees C, extrapolated from isothermal studies, were much lower for indorenate hydrochloride after tumbling mixing with microcrystalline cellulose (3.45 x 10(-5) day-1) than those obtained after tumbling mixing with lactose (112.0 x 10(-5) day-1). Distribution of the drug on the excipient's surface, through granulation with and without Povidone, increased the average drug degradation rates in granules with microcrystalline cellulose (36.2 x 10(-5) day-1) as well as in granules with lactose (326 x 10(-5) day-1). Partially amorphous lactose (spray-dried lactose) showed higher average degradation rates (310.5 x 10(-5) day-1) than crystalline lactose (199.3 x 10(-5) day-1). It appears that the amorphous portion of the drug as well as that of reacting excipients play a major role in affecting the reaction rate. The calorimetric studies showed a strong solid-solid interaction between indorenate hydrochloride and lactose, suggesting chemical incompatibility. This strong solid-solid interaction was characterized by disappearance of typical transition peaks of lactose at temperatures above 200 degrees C and the development of new peaks at about 130-170 degrees C. No major changes in transition peaks were observed in mixtures of microcrystalline cellulose and indorenate hydrochloride, suggesting chemical compatibility. Calorimetric results allow the prediction of the chemical incompatibility between indorenate hydrochloride and lactose observed in isothermal degradation studies.

5-Methoxytryptamine↗
PubMed2002

Comparative evaluation of co-processed lactose and microcrystalline cellulose with their physical mixtures in the formulation of folic acid tablets.

In this study, a new co-processed filler-binder ingredient for direct compression, MicroceLac 100, was compared with three different lactoses mixed with microcrystalline cellulose. The aim was to improve a folic acid tablet formulation. Therefore, the influence of drug addition to these mixtures was studied with regard to flow and binding properties. Another part of the study was focused on the interaction and segregation behavior of the drug. MicroceLac 100 showed superior flow and binding properties. Good adhesion of folic acid to the MicroceLac 100 particles could decrease demixing and segregation. The improved characteristics of co-processed material are attributed to spray drying. Sodium stearyl fumarate was chosen as a lubricant, based on ejection force measurements. The content uniformity of the newly formulated direct compression tablets met the official requirements.

Adhesiveness↗
PubMed2003

Exploration of melt granulation technique for the development of coprocessed directly compressible adjuvant containing lactose and microcrystalline cellulose.

The objective of the present investigation was to prepare and evaluate lactose and microcrystalline cellulose based, directly compressible adjuvant using melt granulation technique. The percentage of polymer blend (PVP K 30 and PEG 4000; 5, 10, or 15%) and the polymer blend ratio (9:1, 1:1, or 1:9) were selected as independent variables in a 3(2) full factorial design. The lactose and microcrystalline cellulose blend (3:1) was mixed with the meltable binder on a water bath at 90 degrees C. The agglomerates were cooled to 35 degrees C and subsequently passed through 30 mesh. A batch containing 12.5% of the polymer blend containing 1:9 ratio of PVP:PEG was used for further studies. In an another 3(2) full factorial design, disintegrant (crospovidone, croscarmellose sodium, or sodium starch glycolate) and mode of addition of disintegrant (intragranular, extragranular, or combination of intragranular and extragranular) were used as independent variables. The agglomerates were evaluated for percentage fines and Carr's index. Tablets were prepared on a single-punch tablet machine, and they were evaluated for tensile strength, friability, and disintegration time. Regression analysis was carried out to evolve full and refined models. Contour plots are presented for graphical expression of the results. The use of composite index is demonstrated for the selection of an appropriate batch. The disintegration time of tablets reduced from 18 min to 6 min when 6% crospovidone was included in the product. The optimized adjuvant was characterized for particle size distribution, granular friability, Kawakita's and Kuno's equation, and dilution potential study. Turmeric, glycyrrhiza, acetaminophen, and metformin HCl were used as model drugs for the preparation of tablets. The present study underlines the fact that melt granulation technique may be adopted for the development of multifunctional directly compressible adjuvant for use in pharmaceuticals. The advantages of melt granulation technique over the classical wet granulation and spray-drying are presented.

Adjuvants, Pharmaceutic↗
PubMed2005

Compression of controlled-release pellets produced by a hot-melt extrusion and spheronization process.

The purpose of this study was to investigate the physicomechanical and dissolution properties of tablets containing controlled-release pellets prepared by a hot-melt extrusion and spheronization process. A powder blend of anhydrous theophylline, Eudragit Preparation 4135 F, and functional excipients was melt-extruded, pelletized, and then spheronized. The pellets were compressed into tablets using forces of 5, 10, 15, and 20 kN. Tablet diluents included microcrystalline cellulose, a mixture of spray-dried lactose and microcrystalline cellulose, modified food starch, and soy polysaccharides. The effective porosity of the compressed pellets was measured using mercury porosimetry and helium pycnometry, while the surface area was determined using Brunauer, Emmett, and Teller (BET) analysis. The disintegration time, hardness, and friability of compacts were determined. Drug release studies were performed according to USP 27 Apparatus 3 guidelines in 250 mL of medium (pH 1.0, 3.0, 5.0, 6.8, and 7.4) 37 degrees C and 20 dpm. Samples were analyzed by high pressure-liquid chromatography (HPLC). Effective porosity and surface area determinations of the melt-extruded pellets were not influenced by compression. The percent of theophylline released from rapidly disintegrating tablets was not affected by compression force or excipient selection, but tablets with prolonged disintegration times exhibited delayed drug release in acidic media. However, dissolution profiles of uncompressed pellets and all compacts were identical after transition from 0.1 N HCl to media increasing in pH from 3.0 to 7.4. Furthermore, pellet to filler excipient ratio and filler excipient selection did not influence the rate of drug release from compacts.

Chemistry, Pharmaceutical↗