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1.
Pharm Res ; 33(6): 1527-41, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26943943

RESUMO

PURPOSE: To compare drug deposition in the nose and olfactory region with different nasal devices and administration techniques. A Sar-Gel based colorimetry method will be developed to quantify local deposition rates. METHODS: A sectional nasal airway cast was developed based on an MRI-based nasal airway model to visualize deposition patterns and measure regional dosages. Four nasal spray pumps and four nebulizers were tested with both standard and point-release administration techniques. Delivered dosages were measured using a high-precision scale. The colorimetry correlation for deposited mass was developed via image processing in Matlab and its performance was evaluated through comparison to experimental measurements. RESULTS: Results show that the majority of nasal spray droplets deposited in the anterior nose while only a small fraction (less than 4.6%) reached the olfactory region. For all nebulizers considered, more droplets went beyond the nasal valve, leading to distinct deposition patterns as a function of both the nebulizer type (droplet size and initial speed) and inhalation flow rate. With the point-release administration, up to 9.0% (±1.9%) of administered drugs were delivered to the olfactory region and 15.7 (±2.4%) to the upper nose using Pari Sinus. CONCLUSIONS: Standard nasal devices are inadequate to deliver clinically significant olfactory dosages without excess drug losses in other nasal epitheliums. The Sar-Gel based colorimetry method appears to provide a simple and practical approach to visualize and quantify regional deposition.


Assuntos
Anti-Inflamatórios/administração & dosagem , Modelos Anatômicos , Nebulizadores e Vaporizadores , Nariz/anatomia & histologia , Bulbo Olfatório/anatomia & histologia , Administração por Inalação , Adulto , Aerossóis , Anti-Inflamatórios/metabolismo , Colorimetria , Desenho de Equipamento , Humanos , Imageamento por Ressonância Magnética , Masculino , Mucosa Nasal/metabolismo , Nariz/diagnóstico por imagem , Bulbo Olfatório/diagnóstico por imagem , Bulbo Olfatório/metabolismo , Fatores de Tempo
2.
Int J Pharm ; 520(1-2): 254-266, 2017 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-28189854

RESUMO

BACKGROUND: Pulsating aerosol delivery has been demonstrated in depositing medications into paranasal sinuses. However, its mechanisms are not fully understood. Influences of the nasal anatomy and sound frequency on intrasinus delivery are not yet clear. OBJECTIVES: This study aimed to gain a better understanding of the mechanisms for enhanced intrasinus delivery with pulsating sound. Specifically, effects of the pulsation frequency, ostium size, and sinus shape on the intrasinus dosage and resonance frequency would be examined. METHODS AND MATERIALS: Both experiments and computational modeling were conducted to understand the pulsating aerosol delivery in both idealized (two-bottle) and realistic nose-sinus models. A computational model of intrasinus pulsation delivery was developed using COMSOL and was cross-validated with both experimental and theoretical results. RESULTS: In contrast to previous studies, seemingly erratic relations between the intrasinus dosage and ostium diameter were observed in experiments, which suggested a more complicated particle transport mechanism. Improved agreement was achieved when grouping the ostium size and sinus volume into the resonance frequency, and therefore, validated the hypothesis that intrasinus deposition strongly depends on the resonance frequency. Extensive computational simulations revealed that the deposition was highest at the resonance frequency and decreased gradually at off-resonance frequencies. The resonance frequency depended on the ostium and sinus morphology, but was independent of the nasal cavity. CONCLUSION: Results of this study verified the hypothesis of resonance being the mechanism for enhanced particle deposition in the maxillary sinus. A better knowledge of the relationship between sinus dosages, pulsating frequency, and nasal morphometry is essential for improving the design of intrasinus delivery devices.


Assuntos
Aerossóis/farmacocinética , Simulação por Computador , Seio Maxilar/metabolismo , Administração Intranasal , Aerossóis/administração & dosagem , Humanos , Técnicas In Vitro , Seio Maxilar/anatomia & histologia , Cavidade Nasal/anatomia & histologia , Cavidade Nasal/metabolismo , Reprodutibilidade dos Testes , Som
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