Spray-dried particles

There may be competing factors between emulsion size and extractable surface oil that produce these results. While the finer emulsions have less extractable surface oil which should improve shelf-stability, the total surface area of the oil droplets in these powders is greater (Table V). The lower amount of surface oil provides less oil that is openly exposed to oxidation but the greater surface area of the droplets in the carrier matrix provides greater possibility for oxidation once oxygen has permeated the spray dried particles. 

Figure 5. A broken, hollow spray dried particle DEPICTED BY SCANNING ELECTRON MICROGRAPH AT 15 Kv AND 18OOX MAGNIFICATION.

Microcrystalline cellulose is one of the most commonly used filler-binders in direct compression formulations because it provides good binding properties as a dry binder, excellent compactibility, and a high dilution potential. It also contributes good disintegration and lubrication characteristics to direct compression formulas. When compressed, microcrystalline cellulose undergoes plastic deformation. The acid hydrolysis portion of the production process introduces slip planes and dislocations into the material. Slip planes, dislocations, and the small size of the individual crystals aid in the plastic flow that takes place. The spray-dried particle itself, which has a higher porosity compared with the absolute porosity of cellulose, also deforms... 

The physical size of the resulting spray-dried particles is dictated by the mass of solute in each droplet and depends on both the size of the droplets atomized into the hot air stream and the concentration of the feed solution. More dilute solutions permit the formation of larger droplets, while more concentrated solutions require smaller droplets. The appropriate feed concentrations and atomization conditions must also be practical to be commercially viable. For example, doubling the feed concentration halves the amount of water, energy, and time required to produce a unit of drug powder. Typically, the spray-drying parameters can be adjusted to produce particles within the size range needed for alveolar deposition. 

Fig. 3. SEM images of various dry powders for inhalation, (a) Spray-dried particles (see Subheading 3.1.)- Reproduced from ref. 5. (b) Particles prepared by emulsification techniques (see Subheading 3.2.1.), Reproduced from ref. 10. (c) Particles prepared by supercritical C02 swelling (see Subheading 3.2.2.), The particles in panel b were the starting material for these particles. Reproduced from ref. 10. (d) TI particles (see Subheading 3.4.2.),...

Fig. 2.21. Spray dried particles prepared from 50% colloidal silica (-20 nm diameter) and 10% silica derived from polysilicic acid [13].

Alder, M., Unger, M., and Lee, G. (2000), Surface composition of spray-dried particles of bovine serum albumin/trehalose/surfactant, Pharm. Res., 17, 863-870. 

Spray drying involves three fundamental steps (1) atomization, (2) droplet drying, and (3) gas-droplet mixing. Each of these steps will be discussed in the following sections. The particles produced by spray drying are sometimes spherical and other times in the shape of a punctured spherical shell. The distribution of internal stnicture and chemistry including binder are not uniform inside a spray dried particle because it dries from the outside, first bringing impurities finm the center of the droplet to the surface where they are crystallized out or left behind when the solvent evaporates. 

Determine the spray dried particle diameter resulting from the Rayleigh breakup of a jet 1 nun in diameter operating on a 0.001 molar doped iron nitrate solution of Ni—Al-Ga spinel ferrite (i.e., MFe204 M = Nio.5-Alo 3—Gao.2). Assume that the dr3dng conditions are sufficient to evaporate the water but not thermally decompose the hydrated metal nitrates. 

Solid dispersion particles made by spray-drying dis-ulfiram 1 1 or 1 2 (w/w) with PVP and instilled in the rabbit eye were found to have improved concentrations in the aqueous humor compared to 1 1 solid dispersions made by the evaporation method. In both cases, drug particles were passed through a 75 pm sieve. Particle size of the spray-dried particles had a D o of 3.3 0.04 pm, while those prepared by evaporation had a Dso of 34.3 18pm. ° ... 

Some empirical observations can help to understand how the feedstock physical state (i.e., suspension, emulsion, solution) and the physicochemical properties of the formulation components relate to the morphology and surface characteristics of the spray dried particles. As mentioned above shell formation will occur when one of the formulation components reaches its solubility and precipitates leading to the formation of a solid shell that may be either amorphous or crystalline. Low aqueous solubility components tend to precipitate early in the drying process and lend to form corrugated... 

FIG. 21-175 Types of spray-dried particles, depending on drying conditions and feed boiling point. Courtesy Niro Pharma Systems.)... 

The effort that leads to optimization of the particle morphology is largely one of trial and error, and there is no simple means to describe the distribution of components within individual particulates. Clearly, if the majority of an active component (API) is in the interior of a particle, then the dissolution or release characteristics are likely to differ from particles where the API is predominantly on the surface. The surface distribution of proteins and polymers within spray-dried particles has been studied using electron spectroscopy for chemical analysis that involves analyzing the energy signature of electrons scattered from surfaces while being bombarded by x-rays [11,28-31], Conclusions can then be drawn... 

Dunbar CA, Concession NM, Hickey AJ. Evaluation of atomizer performance in production of respirable spray-dried particles. Pharm Dev Technol 3(4) 433 —441, 1998. 

Some spray-dried particles have been prepared using other generally regarded as safe (GRAS) substances such as lecithin, human serum albumin, polylysine, and polyarginine, but these have also not yet been included in approved products for delivery to the lungs. 

Walton, D.E. The morphology of spray-dried particles a qualitative view. Drying TechnoL, 18, 1943, 2000. 

Inner Structural Analysis of Spray-Dried Particle... 

FIGURE 1.12 Schematic illustration of a spray-dried particle in humid air environment. 

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