Micro Aerosol. Physiology, Pharmacology, Therapeutics

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XRPD patterns Fig. SD mannitol samples showed that the peaks remained after the spray-drying process. However, the peak positions and intensity varied with samples.

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The thermograms obtained from mannitol samples are shown in Figure 3 , and detailed values of melting peak enthalpy and temperature are tabulated in Table 3. Table 3.

As with raw D-mannitol, the melting temperature range for SD mannitol was narrow as well. The residual water content in the powders is summarized in Table 4. The water content for SD mannitol increased with spray-drying pump rates from low to high and was higher than that of raw D-mannitol.

The low water content value ruled out the possibility of hemihydrates of mannitol.

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Table 4. Raman spectroscopy is highly sensitive to the polymorphic form of mannitol, as shown by the FT-Raman spectra of bulk samples of each phase in Figure 6a obtained using a 1. The bulk samples of alpha, beta, and delta mannitol were prepared by rapid evaporation from water, slow evaporation from water, and lyophilization, respectively, and were checked by XRPD. The CRM spectra were obtained using a nm laser, as mannitol shows minimal fluorescence. From examination of the map and spectra in Figure 6b and c , the material is seen to be primarily the alpha polymorph of mannitol.

Spectra taken from three individual points in this map are compared in Figure 6c , highlighting the lack of significant differences observed and the close similarity with the reference spectrum of the alpha phase shown in Figure 6a. Figure 7 shows the FTIR spectra of mannitol particles. These are attributed to different mannitol polymorphs.

As indicated in the profile, the SD mannitol powder produced from high spray-drying pump rate exhibited low particle deposition on stage 1 D a50 cutoff diameter of 8. However, compared with the other two formulations, the particle deposition fraction was reduced for particles generated from the high pump rate on stages 5—7 that were in the aerodynamic nanometer size range. The aerosol dispersion performance parameter values are listed in Table 5.

Table 5. The narrow particle size distribution is essentially critical for pulmonary dry powder inhalation, as it enables the aerosols to target a specific lung region without spreading the dose in the whole lungs. Targeted aerosols lower the therapeutic dose and toxic effects. Therefore, they enhance the therapeutic outcome.

In addition, the particle engineering process of spray drying can optimize particle size, shape, as well as morphology, which will result in better aerosol dispersion performance given as dry powder formulations. The narrow particle size distribution with Span values in the range of 1—2 Table 2 theoretically indicates reproducible aerosol particle aerodynamic performance, which is clinically important for therapeutic reproducibility.

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The increased particle size D V50 in Table 2 , particle surface roughness Fig. Mannitol polymorphic behavior has been reported.

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  7. The characteristic peaks of each polymorph in the diffractograms were symboled for identification purpose. The alpha form was identified using the peaks at The peaks at The delta form was validated using a peak at 9. As the pump rate increased, the alpha and beta polymorphic content decreased with increasing polymorphic delta form content based on intensity of the characteristic peaks of each polymorph.

    In contrast, Kumon et al.

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    Reference X-ray patterns of different polymorphs of mannitol obtained from the Cambridge structure database program of ConQuest 1. The solid star symbol indicates characteristic peaks of alpha, beta, and delta mannitol, respectively, which were used for identification in this study. The low water vapor sorption Fig. The MMAD values for all aerosols were suitable for efficiently targeting the smaller airways as inhaled dry powder aerosols. The difference in aerosol dispersion performance among SD mannitol particles may arise from the presence of different polymorphic composition after organic solution advanced spray drying in closed-mode from dilute mannitol solution in methanol, resulting in distinctive physicochemical properties thermal properties, XRPD, water vapor sorption, etc.

    SD mannitol particles from medium and particularly from low pump rates exhibited higher particle deposition on stage 1.

    Inhaled nano- and microparticles for drug delivery

    Those deposited particles on stage 1 represent the aerosolized agglomerates not primary particles. It is known that the interparticulate forces i. The excellent aerosol dispersion properties of such particles can be advantageous in the treatment of CF and other pulmonary diseases by DPIs. The primary SD mannitol particles possessed necessary particle and surface properties that minimize the interparticulate interactions and provide excellent aerosol performance as DPIs. Comprehensive physicochemical characterization of SD mannitol particles indicated that crystallinity was retained following organic solution advanced spray drying due to polymorphic interconversion.

    The type of crystalline polymorphs present were correlated with the spray-drying pump rate. As high-performing DPIs, aerosol deposition patterns for all three pump rates were distinct. Positive linear correlation between aerosol dispersion parameters FPF and RF and spray-drying pump rate revealed this interplay. The authors thank Dr.

    The authors declare that there are no conflicts of interest.

    Carsten Ehrhardt : Trinity Research - Trinity College Dublin

    Login to your account Username. Forgot password? Keep me logged in. New User. Change Password. Old Password. New Password. Password Changed Successfully Your password has been changed. Create a new account Email. Returning user. Can't sign in? Forgot your password? Lam J. In Part I, we review the modes of pulmonary delivery of siRNA, the evaluation of aerosol drug delivery systems, and the rationale for the use of nanocarriers to overcome the barriers of pulmonary delivery and cellular uptake of siRNA.

    Part II focuses on the siRNA loaded non-viral particulates for aerosolized delivery systems, and preparation and characterization techniques for siRNA loaded nanoparticles. To achieve pulmonary delivery, inhalable aerosols generated by an inhaler or nebulizer are the preferred option.


    Driscoll K. Turner P. The most non-invasive way to locally deliver therapeutics to the lungs is through inhalation. Four types of inhalation devices are currently available including pressurized metered dose inhalers pMDIs , dry powder inhalers DPIs , nebulizers, and soft mist inhalers SMIs. With appropriate developmental optimization, these devices may deliver siRNA to the lungs. During development, key parameters should be considered for an optimum inhaler system, as shown in Parameters to consider in siRNA formulation design for inhalation. Sharma K. DPIs and their formulations allow for the inhalation of aerosol clouds of dry particles.

    DPI device design has a major impact on their performance. Feddah M. Ross D. Shoyele S. Bai S. Codrons V. Mastrandrea L. Rawat A. Chan H. Ari A. Dailey L.

    Micro Aerosol. Physiology, Pharmacology, Therapeutics Micro Aerosol. Physiology, Pharmacology, Therapeutics
    Micro Aerosol. Physiology, Pharmacology, Therapeutics Micro Aerosol. Physiology, Pharmacology, Therapeutics
    Micro Aerosol. Physiology, Pharmacology, Therapeutics Micro Aerosol. Physiology, Pharmacology, Therapeutics
    Micro Aerosol. Physiology, Pharmacology, Therapeutics Micro Aerosol. Physiology, Pharmacology, Therapeutics
    Micro Aerosol. Physiology, Pharmacology, Therapeutics Micro Aerosol. Physiology, Pharmacology, Therapeutics
    Micro Aerosol. Physiology, Pharmacology, Therapeutics Micro Aerosol. Physiology, Pharmacology, Therapeutics

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