Enhanced pulmonary absorption following aerosol administration of mucoadhesive powder microspheres

Sakagami, Masahiro; Sakon, Kiyoyuki; Kinoshita, Wataru; Makino, Yuji

doi:10.1016/s0168-3659(01)00475-8

Cited by 62 publications

(30 citation statements)

References 24 publications

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“…Spray dried particulates can be designed by inclusion of polymers such as, hyaluronan, 7) polylactic acid, 8) chitosan, 9) and poly(lacticco-glycolic acid). 10) Among the cellulose based poly-mers, hydroxypropyl cellulose 11) and hydroxypropyl methyl cellulose 12) have been studied for inhalation delivery. Recently, suspension of spray dried sodium carboxymethyl cellulose (SC) powder was found to be a promising alternative in the pressurized metered dose inhalation delivery of bovine serum albumin.…”

Section: Introductionmentioning

confidence: 99%

Formulation Optimization and Characterization of Spray Dried Microparticles for Inhalation Delivery of Doxycycline Hyclate

Mishra

2011

YAKUGAKU ZASSHI

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The local delivery of antibiotics in the treatment of infectious respiratory diseases is an attractive alternative to deliver high concentration of antimicrobials directly to the lungs and minimize systemic side eŠects. In this study, inhalable microparticles containing doxycycline hyclate, sodium carboxymethylcellulose, leucine and lactose were prepared by spray drying of aqueous ethanol formulations. Box-Behnken design was used to study the in‰uence of various independent variables such as polymer concentration, leucine concentration, ethanol concentration and inlet temperature of the spray dryer on microparticle characteristics. The microparticles were characterized in terms of particle morphology, drug excipient interaction, yield, entrapment e‹ciency, Carr's index, moisture content, thermal properties, X-ray powder diŠraction, aerosolization performance and in vitro drug release. The eŠect of independent variables on spray dryer outlet temperature was also studied. The overall shape of the particles was found to be spherical like doughnuts in the size range of 1.16 5.2 mm. The optimized formulation (sodium carboxymethylcellulose concentration 14％ w/v, leucine concentration 33％ w/v, ethanol concentration 36％ v/v, inlet temperature of 140°C) exhibited the following properties: yield 56.69％, moisture content 3.86％, encapsulation e‹ciency 61.74％, theoretical aerodynamic diameter 3.11 mm and Carr's index 23.5％ at an outlet temperature 77°C. The powders generated were of a suitable mass median aerodynamic diameter (4.89 mm) with 49.3％ˆne particle fraction and exhibited a sustained drug release proˆle in vitro.

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Section: Introductionmentioning

confidence: 99%

Formulation Optimization and Characterization of Spray Dried Microparticles for Inhalation Delivery of Doxycycline Hyclate

Mishra

2011

YAKUGAKU ZASSHI

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“…2, was modified from our previous system (Sakagami et al 2001(Sakagami et al , 2002a and validated in-house. Powder aerosols of fluorescein were generated using a dust-feeder (DF-3; Shibata Sci Tech Ltd., Tokyo, Japan) employing 60 l air /min of filtered-dry air, and introduced into a custom-made aerosol chamber (100 l; Fig.…”

Section: Intravenous Fluorescein Administrationmentioning

confidence: 99%

“…Fluorescein in the biological samples was analyzed by validated HPLC coupled with fluorescence detection (excitation and emission wavelengths of 485 and 515 nm, respectively; LC-6 and RF-530, Shimadzu Corporation, Kyoto, Japan), which were described in detail previously (Sakagami et al 2001). Briefly, lung tissues were homogenized (Polytoron; Kinematica AG, Littau, Switzerland) in 0.01 M phosphate buffer (pH 10) at 4°C.…”

Section: Fluorescein Analysismentioning

confidence: 99%

Fractional contribution of lung, nasal and gastrointestinal absorption to the systemic level following nose-only aerosol exposure in rats: a case study of 3.7-µm fluorescein aerosols

et al. 2003

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Because absorption takes place from multiple sites of aerosol deposition, it is generally difficult to interpret systemic levels following nose-only inhalation in laboratory rodents. Therefore, this study attempted to determine the fractional contribution of lung, nasal and gastrointestinal (GI) absorption to the observed systemic level following nose-only aerosol exposure in rats using fluorescein as a model powder solute. Rats were treated orally with vehicle or activated charcoal, the latter diminishing GI absorption of fluorescein, and were subsequently nose-only exposed to 3.7- micro m fluorescein aerosols at 25.2 micro g/l(air) for 10 min. While fluorescein similarly disappeared from the lung at a half-life of 0.23 hr, its plasma concentrations in the charcoal-treated group were significantly lower than those in the charcoal-untreated (vehicle) group. This suggests that significant portions of fluorescein were transported by nasopharyngeal and tracheobronchial mucociliary clearances following aerosol exposure and were absorbed from the GI tract. Despite the lack of GI absorption in the charcoal-treated animals, it was estimated that this nose-only exposure of fluorescein allowed 25.7 and 82.5 micro g/kg of simultaneous lung and nasal deposition, respectively, followed by their absorption composing the observed systemic level in this group (AUC(0- infinity ) 137.49 ng/ml h). Thus, assuming linear pharmacokinetics of fluorescein, the extent of absorption (AUC(0- infinity )) due to such nasal deposit (82.5 micro g/kg) was estimated to be 47.00 ng/ml h using the AUC(0- infinity ) obtained in an independent study of intranasal powder insufflation at 34.5 micro g/kg in the charcoal-treated rats (AUC(0- infinity ) 19.66 ng/ml h). As a result, the AUC(0- infinity ) due to 25.7 micro g/kg of the lung deposit was deconvoluted to be 90.49 ng/ml h and finally, the absolute bioavailability (F%) of the "lung-region-specific" deposition and absorption of fluorescein was estimated to be 55.0%. It is observed therefore, that lung, nasal and GI absorption accounted for 24.2, 12.5 and 63.3% of the total fluorescein absorption, respectively, following nose-only exposure of 3.7- micro m aerosols. This study addresses the common methodological insufficiency of nose-only inhalation studies in rodents, which have been neglected in most cases, and provides the appropriate kinetic interpretation for their observed systemic level.

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“…It is an approved food additive that has been considered for pharmaceutical formulation and drug delivery applications, in which attention has been focused on its absorption-enhancing, controlled release and bioadhesive properties. Recently, chitosan-based delivery systems have been proposed to increase the bioavailability of drugs both at the nasal mucosa and in the lungs [19,20]; also these systems have been reported as efficient vehicles for pulmonary gene delivery [21][22][23]. Nevertheless chitosan is not included in the FDA Inactive Ingredient Guide and very sparse data on its pulmonary toxicity are available.…”

Section: Introductionmentioning

confidence: 99%

Preparation and In Vitro Evaluation of Budesonide Spray Dried Microparticles for Pulmonary Delivery

Naikwade

2009

Sci. Pharm.

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The present study describes development and in vitro evaluation of budesonide microparticles prepared by spray drying for delivering drug directly to lungs via dry powder inhaler. This paper introduces new formulations for pharmaceutical applications which includes conventional formulations and novel spray dried microparticles viz., pulmosols, microspheres and porous particles. Optimized spray drying parameters for generation of microparticles were: inlet temperature, 130 °C; outlet temperature, 80 °C; aspirator rate, 240 mWc (60%); solution feed rate, 2 ml/min; spraying air flow pressure, 2 bar. Microparticles appeared to be spherical, low-density particles characterized by smooth surface. MMAD and GSD ranged from 2.5-4.6 µm and 1.5-2.7 respectively. Effective index of microspheres (54.48) and porous particle formulations (64.22) was higher than the conventional formulation (49.21) indicating more effective deposition of microparticles to the lungs. Carr's Index (20-30%) and Hausner ratio (1.2-1.7) for all formulations indicated good powder flow properties. Formulations emitted a fine particle fraction of 25-47%. Microparticles showed extended in vitro drug release upto 4 hours with high respirable fractions, thus use of microparticles potentially offers sustained release profile along with improved delivery of drug to the pulmonary tract.

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Enhanced pulmonary absorption following aerosol administration of mucoadhesive powder microspheres

Cited by 62 publications

References 24 publications

Formulation Optimization and Characterization of Spray Dried Microparticles for Inhalation Delivery of Doxycycline Hyclate

Formulation Optimization and Characterization of Spray Dried Microparticles for Inhalation Delivery of Doxycycline Hyclate

Fractional contribution of lung, nasal and gastrointestinal absorption to the systemic level following nose-only aerosol exposure in rats: a case study of 3.7-µm fluorescein aerosols

Preparation and In Vitro Evaluation of Budesonide Spray Dried Microparticles for Pulmonary Delivery

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