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      A Radiometric Study of Factors Affecting Drug Output of Jet Nebulizers

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          Abstract

          Jet nebulizers show an unreasonable variation in drug output and nebulization rates that leads to clinical and regulatory problems. Current evaluation methods appear inadequate for the purpose. Our objective was to evaluate Technetium-99m radiometry to study nebulizer parameters and the factors influencing it quantitatively. Drug output, output rate and residual mass and the effect of excipient, temperature, surface tension, air-jet speed, and equipment brand and aging were studied. Though nebulization of radiolabeled drugs followed first-order kinetics, the rates were significantly different; the heaviest drug (Tc-99m colloid) and Tc-99m salbutamol had the least nebulization. Nebulization rate for the first minute was invariably higher than the mean rate signifying the concentration effect of the solute. Drug residue was 35-75%. Drug output of different nebulizer chamber and air compressor brands was different to the extent of 270% and 180% respectively. ‘Aging’ of fluid chamber, cold drug fluid and obstruction in air-jet resulted in significant reduction in output, while addition of 2% saline as excipient did not change the output rate. Addition of ethyl alcohol resulted in a maximum of 260% enhancement (with Tc-99m salbutamol), while further reduction in surface tension was counterproductive irrespective of the drug used. We conclude that radiometry can provide valuable parametric information on the performance of different jet nebulizers.

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          Most cited references52

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          The science of nebulised drug delivery.

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            Targeted drug-aerosol delivery in the human respiratory system.

            Inhalation of drug aerosols is a modern pathway to combat lung diseases. It is also becoming the preferred route for insulin delivery, pain management, cancer therapy, and nanotherapeutics. Popular delivery devices include nebulizers, metered-dose inhalers, and dry-powder inhalers. They are all nondirectional and hence have typically low particle deposition efficiencies in desired nasal or lung areas. Thus, for specific disease treatment with costly and/or aggressive medicine, it is necessary to provide targeted drug-aerosol delivery to predetermined sites in the human respiratory system. Experimental measurements and computer models of particle transport and deposition in nasal and lung airway models are presented. Furthermore, the underlying methodology and performance of pressurized metered dose inhalers as well as new smart inhaler systems are discussed. To maximize respiratory drug delivery to specific sites, an optimal combination of particle characteristics, inhalation waveform, particle release position, and drug-aerosol dosage has to be achieved.
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              Formulation of rifampicin-cyclodextrin complexes for lung nebulization.

              Lung administration of antibiotics by nebulization is promising for improving treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like rifampicin, cyclodextrins (CD) may improve lung delivery by permitting higher dosing. For this purpose, we investigated rifampicin-CD complexes in terms of rifampicin apparent solubility enhancement, effect on in vitro permeability on Calu-3 broncho-alveolar cells, effect on in vitro antibacterial activity against Acinetobacter baumannii and nebulization characteristics measured by NGI cascade impactor. Complexation efficiency between rifampicin and methylated beta-cyclodextrin (RAMEB) or hydroxypropyl-beta-cyclodextrin (HPbetaCD) was pH-dependent, involving the piperazin group. Rifampicin phase solubility diagrams constructed at pH 9 showed an A(L)-type curve for RAMEB and a B(S)-type for HPbetaCD. Stability constants calculated for a 1:1 molar ratio of CD/rifampicin were 73.4 +/- 8.2 M(-1) for RAMEB and 68.5 +/- 5.2 M(-1) for HPbetaCD. Complexes with RAMEB or HPbetaCD increased 22 times and 7.6 times respectively the apparent solubility of rifampicin and were found to be satisfactorily stable for 2 days when diluted in a solution at physiological pH. The nebulization of the complex solution created droplets in size range compatible with pulmonary deposition. Furthermore, the presence of HPbetaCD decreased the MMAD of the aerosolized droplets. Activity of RAMEB and HPbetaCD complexes measured by the total rifampicin MIC against A. baumannii was similar or lower to free rifampicin MIC respectively. Complexation did not alter the rifampicin permeability in the timescale of 1h as evaluated with a Calu-3 epithelial cell model, but acted as a reservoir for rifampicin. In conclusion, this work reports that CDs can be used as vectors for pulmonary nebulization to increase the amount of active rifampicin and optimize its lung pharmacokinetic profile.
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                Author and article information

                Journal
                Indian J Pharm Sci
                IJPhS
                Indian Journal of Pharmaceutical Sciences
                Medknow Publications (India )
                0250-474X
                1998-3743
                Jan-Feb 2010
                : 72
                : 1
                : 31-38
                Affiliations
                Institute of Nuclear Medicine and Allied Sciences, Defence R & D organization, Brig. S. K. Mazumdar Road, Delhi-110 054, India
                Author notes
                [* ] Address for correspondence E-mail: dr.aseembhatnagar@ 123456gmail.com
                Article
                IJPhS-72-31
                10.4103/0250-474X.62234
                2883224
                20582187
                e67a3b46-3aa3-412b-ad1f-3a6b0d85a87c
                © Indian Journal of Pharmaceutical Sciences

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 April 2009
                : 01 October 2009
                : 18 December 2009
                Categories
                Research Paper

                Pharmacology & Pharmaceutical medicine
                technetium-99m,radiometry,jet nebulizer performance
                Pharmacology & Pharmaceutical medicine
                technetium-99m, radiometry, jet nebulizer performance

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