Mannitol particles

Littringer EM, Paus R, Mescher A, Schroettner H, Walzel P, Urbanetz NA (2013) The morphology of spray dried mannitol particles—the vital importanceof droplet size. Powder Technol 239 162-174... 

Fig. 6.5 SEM of mannitol particles obtained from 15wt% solution at a d er exhaust temperature of (a) 80°C and (b) 130°C.

The variety of parameters allowed the synthesis of mannitol particles with different morphological characteristics. Smaller droplets with their higher surface-to-volume ratio and therefore higher evaporation rate exhibited an enhanced porosity 0, defined by Eq. (4.7) ... 

Figure 4.33 shows four mannitol particles as an example of each category dried under different experimental conditions. 

The contour plot shows a Unear dependence on the initial mannitol mass fraction and a quadratic dependence on the drying temperature. It confirms the observation that the surface of the dried mannitol particles gets rougher with increasing temperature and initial mannitol mass fraction. However, this categorization by voltm-teers is very subjective and the quality of the model is poor which is confirmed by low values of / = 0.510 and = 0.364 in the DoE results. The model vahdity... 

Fig. 4.33 Examples of mannitol particles for the categorization of surface textures at different initial drying conditions [40]...

Fig. 4.34 Contour plot of the surface texture of mannitol particles for initial mannitol mass fraction versus drying temperature. The initial droplet diameter is 470 pm...

Fig. 9.5 Evaporation of mannitol-water droplets at different drying temperatures, Fmo= 10%. (a) Normalized droplet surface area versus time (Reprinted with permissirm fiom [33] ASME). (b) Porosity of the final mannitol particles vctsus drying temperature, do = 450 )rm (Reprinted with permission from [34] Eisevier)...

Table 9.1 Comparison of numerical and experimental final mannitol particle porosities (Reprinted with permission from [31] Elsevier)...

Two samples (indented and spherical mannitol particles) were suspended in tissue freezing medium on a sample holder (—25 °C) and sectioned (5 pm thickness) using a cryomicrotome (CryoStar NX 70, Thermo Scientific, Waltham, MA, USA). Process temperature was set to —24 C for the cutting process. The cross sections were then placed on an SEM sample holder and prepared for SEM analysis as described in Sect. 2.2.7. 

Table 14.4 shows the appropriate particle size distributions for 70 and 100 °C outlet temperature. As expected from droplet size results, the LamRot atomiser generated the largest mannitol particles followed by the Niro rotary atomiser and the Caldyn nozzle. 

Earlier experiments by Maas et al. [49] found that mannitol particles dried at lab scale show different surface stmctures than particles dried at pilot scale, which was further related to the different droplet sizes generated by the different atomisers used. To ensure that these findings occur without impact of dryer size or drying capacity, aU experiments were performed with the same pilot scale spray dryer, but with the different atomisers. Figure 14.4 verifies the results found by Maas... 

Littringer, E. M.,Paus, R., Mescher, A., Schroettner, H., Walzel, P., Urbanetz, N. A. (2013). The morphology of spray dried mannitol particles—The vital importance of droplet size. Powder Technology, 239, 162-174. 

The morphology especially of spray-dried Mannitol particles can be systematically controlled by the drying conditions and could be then used as a carrier. Depending on the drying rate, different appearances of the carrier particles are obtained as illustrated in Fig. 22.26. 

Figure 3 Examples of particle morphology for (A) microcrystalline cellulose, (B) lactose, (C) calcium phosphate dibasic, and (D) mannitol. Two images for each material representing different grades.

Tonicity agents are added to injectable preparations to prevent osmotic shock at the site of injection upon administration, and thereby reduce local irritation. Typical excipients used for tonicity adjustment include saline, glycerin, mannitol, dextrose, and trehalose. Tonicity is a colligative property that depends primarily on the number of dissolved particles in solution. Hence, the amount of tonicity agent to be added depends on the specific formulation. Typically, osmolality of 280 to 320mOsm is considered iso-osmotic. 

O Sullivan discussed the influence of particle size on quantitative Raman monitoring in slurries [40], A system of P-form D-mannitol in toluene in the presence of sucrose was studied. It was found that although keeping the number and size of mannitol crystals constant the measured Raman signal varied with different particle size of the sucrose. These results show that particle size must always be taken into consideration in quantitative measurements and a linear relationship can not be taken for granted. 

Fig. 3.19. Heat flow as a function of time during rewarming of the samples measured by DSC. (a) 11% mannitol in 10 mM Tris buffer, pH 7.4 (b) 35 pmol lipid/mL, 11.2% mannitol in 10 mM Tris buffer, pH 7.4, inside the vesicles as well as in the surounding medium, particle size 0.32 pm (c) 33 mmol lipid/mL,...

These treatments convert to ionic substances, and remove, nearly all constituents of natural materials the acid treatments release any inositol present as phosphate, or combined in phospholipids, glycosides, etc. Glycerol remains in the deionized sample, but it can be oxidized separately, or be removed by heat decomposition or by repeatedly evaporating the solution to dryness. Such polyhydric alcohols of greater chain length as erythritol and mannitol, when present, would still interfere. However, corrections can be made for these compounds by determining the formaldehyde which they form on periodate oxidation, or they may be removed by chromatography on filter paper. The micro-periodate method is well suited to the analysis of samples eluted from filter paper, provided that care is exercised to remove the tiny particles of cellulose which are usually found in such eluates. 

Powders intended for nasal administration have to be optimized in terms of particle size and morphology as these properties are related to potential irritation in the nasal cavity [23], Certain procedures (e.g., spray drying process) can modify the particle size of the drug powder raw material, but in order to optimize the morphology and flowability properties of some pure drug powders, excipients need to be used. Sacchetti et al. [28] reported that the use of mannitol as a filler and hydroxy-propylmethyl cellulose (HPMC) as a shaper of spray-dried caffeine microparticles modified the typical needle shape of spray-dried caffeine to a more convenient roundish shape. Further addition of polyethylene glycol (PEG) resulted in increased... 

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