Nano-salbutamol dry powder inhalation: A new approach for treating broncho-constrictive conditions

Bhavna, Kumar; Ahmad, Feroz; Mittal, Gaurav; Jain, Gaurav K.; Malhotra, Geena; Khar, Roop K.; Bhatnagar, Aseem

doi:10.1016/j.ejpb.2008.09.018

Cited by 95 publications

(39 citation statements)

References 32 publications

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“…Whole lung deposition was in the range of 80.2 ± 6.8 for nebulized nano AS respiratory fluid, while the rest was deposited in oropharynx compartment, representing oropharynx, esophagus and stomach. It is much less in comparison to that reported for micronized drugs, where nearly two-third of the drug is deposited in the oral region and is not available to the lungs (Bhavna et al, 2009). The results indicate that significantly increased levels of the antidote can be targeted to the lungs with this novel formulation.…”

Section: Gamma Scintigraphy Studymentioning

confidence: 74%

“…In vitro ACI data showed that use of a large volume spacer resulted in further improvement in respirable fraction of the submicronic AS formulation (82.6 ± 3.1%) as compared to when no spacer was used (65.2 ± 5.2%), suggesting higher lung penetration potential and drug bioavailability. Human scintigraphy studies further highlighted the advantage of submicronic test formulation with lung scintigrams showing nearly 80% of the inhaled drug reaching the pulmonary vasculature, which is much more in comparison to that reported for micronized drugs, where nearly two-third of the drug is deposited in the oropharyngeal region and is not available to the lungs (Bhavna et al, 2009). The blood bioavailability curve with respect to AS post nebulization in humans was favorable by way of a much earlier bioavailability of the antidote in the therapeutic range (6-8 ng/ml) as compared to known values of AS given through intramuscular route, where the therapeutic concentration is achieved at 30 min (Kehe et al, 1992;Ali et al, 2009).…”

Section: Discussionmentioning

confidence: 93%

“…Further, clinical utility of AS nebulization in terms of its early bioavailability in blood was also evaluated in healthy human volunteers. Another highlight of the study is the use of gamma scintigraphy in development and evaluation of the present formulation; a technique which we have successfully used for our drug development program in the past (Ali et al, 2009;Bhavna et al, 2009;Rajpal et al, 2009Rajpal et al, , 2010Kumar et al, 2011;Ali et al, 2013;Sultana et al, 2014). We quantified total and regional lung deposition of nebulized AS using scintigraphy.…”

Section: Introductionmentioning

confidence: 99%

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Development and clinical study of submicronic-atropine sulphate respiratory fluid as a novel organophosphorous poisoning antidote

et al. 2014

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Context: Increased use of organophosphate insecticides (OPI) and possibility of terror groups using stocks of nerve agents underscore the need to develop effective and safe antidotes. While intramuscular administration of antidotes like atropine sulphate (AS) has certain lacunae, intravenous route may not be always feasible in emergency field conditions. Objective: Objective was (a) to develop a novel inhalable submicronic-AS respiratory fluid as potential antidote for OPI poisoning, (b) in-vitro and in-vivo evaluation in terms of respiratory fraction, and (c) clinical study to assess drug bioavailability in blood and atropinization pattern post-inhalation. Methods: Formulation was optimized on the basis of particle size of aerosolized droplets and in-vitro nebulization rate. Anderson cascade impaction (ACI) studies were carried out to validate the advantage of test formulation in terms of respirable fraction. Six healthy volunteers were inhaled the test formulation and blood bioavailability and atropinization were noted serially. Gamma scintigraphy was used to quantify total and regional lung deposition of nebulized AS in-vivo. Results: The formulation was optimized using 30% ethanol-saline with particle size in the range of 350-500 nm. In-vitro ACI data showed high respirable fraction (82.6 ± 3.1%) for the test formulation. In-vivo scintigraphy suggested whole lung deposition of 80.2 ± 6.8% of the total inhaled dose. Early blood bioavailability and atropinization pattern confirmed that therapeutic concentration of the drug in blood was reached within 5 min. Conclusions: 3% submicronic-AS respiratory fluid might be used as potential prophylactic/ therapeutic option against OPI poisoning with several advantages over intramuscular injection, including early blood bioavailability and atropinization.

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Section: Gamma Scintigraphy Studymentioning

confidence: 74%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Development and clinical study of submicronic-atropine sulphate respiratory fluid as a novel organophosphorous poisoning antidote

et al. 2014

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“…Radiolabeling efficiency of CaNa 2 EDTA with Tc-99m was characterized on the basis of serum and saline stability up to 24 h as per previously reported methods using a gamma counter (Capintec, USA) (10,23).…”

Section: Radiolabeling Of Ca-na 2 Edtamentioning

confidence: 99%

“…Another highlight of the study is the use of gamma scintigraphy in the development and evaluation of this oral formulation, a technique which we have successfully used in the development of a few of our other drug formulations too (8)(9)(10)(11)(12). We have studied gastric retention time of the developed formulation by radiolabeling Ca-Na 2 EDTA with technetium99m (Tc-99m).…”

Section: Introductionmentioning

confidence: 99%

Development and Optimization of Gastro-Retentive Controlled-Release Tablet of Calcium-Disodium Edentate and its In Vivo Gamma Scintigraphic Evaluation

et al. 2015

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ABSTRACT. Medical management of heavy metal toxicity, including radioactive ones, is a cause for concern because of their increased use in energy production, healthcare, and mining. Though chelating agents like EDTA and DTPA in parenteral form are available, no suitable oral formulation is there that can trap ingested heavy metal toxicants in the stomach itself, preventing their systemic absorption. The objective of the present study was to develop and optimize gastro-retentive controlled-release tablets of calcium-disodium edentate (Ca-Na 2 EDTA). Gastro-retentive tablet of Ca-Na 2 EDTA was prepared by direct compression method. Thirteen tablet formulations were designed using HPMC-K4M, sodium chloride, and carbopol-934 along with effervescing agents sodium bicarbonate and citric acid. Tablet swelling ability, in vitro buoyancy, and drug dissolution studies were conducted in 0.1 N HCl at 37±0.5°C. Ca-Na 2 EDTA was radiolabeled with technetium-99m for scintigraphy-based in vivo evaluation. Formula F8 (Ca-Na 2 EDTA 200 mg, carbopol 100 mg, avicel 55 mg, citric acid 30 mg, NaHCO 3 70 mg, NaCl 100 mg, and HPMC 95 mg) was found to be optimum in terms of excellent floating properties and sustained drug release. F8 fitted best for KorsmeyerPeppas equation with an R 2 value of 0.993. Gamma scintigraphy in humans showed mean gastric retention period of 6 h. Stability studies carried out in accordance with ICH guidelines and analyzed at time intervals of 0, 1, 2, 4, and 6 months have indicated insignificant difference in tablet hardness, drug content, total floating duration, or matrix integrity of the optimized formulation. Gastro-retentive, controlled-release tablet of CaNa 2 EDTA was successfully developed using effervescent technique as a potential oral antidote for neutralizing ingested heavy metal toxicity.

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Pharmaceutical Aerosols and Pulmonary Drug Delivery

2013

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Nano-salbutamol dry powder inhalation: A new approach for treating broncho-constrictive conditions

Cited by 95 publications

References 32 publications

Development and clinical study of submicronic-atropine sulphate respiratory fluid as a novel organophosphorous poisoning antidote

Development and clinical study of submicronic-atropine sulphate respiratory fluid as a novel organophosphorous poisoning antidote

Development and Optimization of Gastro-Retentive Controlled-Release Tablet of Calcium-Disodium Edentate and its In Vivo Gamma Scintigraphic Evaluation

Pharmaceutical Aerosols and Pulmonary Drug Delivery

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