Searching for physiologically relevant in vitro dissolution techniques for orally inhaled drugs

Radivojev, Snezana; Zellnitz, Sarah; Paudel, Amrit; Frőhlich, Eleonore

doi:10.1016/j.ijpharm.2018.11.072

Cited by 43 publications

(25 citation statements)

References 117 publications

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“…Dissolution in simulated gastric and intestinal fluids in combination with permeability across Caco-2 monolayers provides a good prediction of bioavailability for oral formulations. Simulated lung fluids may also be a tool to assess orally inhaled formulations and various fluids with similar pH and osmolarity but different amounts of antioxidant, lipid, and protein have been used [102]. Speed of dissolution has an importance on availability for poorly water-soluble drugs because not dissolved particles can be removed by mucociliary clearance and uptake by AMs.…”

Section: In Vitro Models To Assess Biological Processesmentioning

confidence: 99%

Biological Obstacles for Identifying In Vitro-In Vivo Correlations of Orally Inhaled Formulations

Frőhlich

2019

Pharmaceutics

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Oral inhalation of drugs is the classic therapy of obstructive lung diseases. In contrast to the oral route, the link between in vitro and in vivo findings is less well defined and predictive models and parameters for in vitro-in vivo correlations are missing. Frequently used in vitro models and problems in obtaining in vivo values to establish such models and to identify the action of formulations in vivo are discussed. It may be concluded that major obstacles to link in vitro parameters on in vivo action include lack of treatment adherence and incorrect use of inhalers by patients, variation in inhaler performance, changes by humidity, uncertainties about lung deposition, and difficulties to measure drug levels in epithelial lining fluid and tissue. Physiologically more relevant in vitro models, improvement in inhaler performance, and better techniques for in vivo measurements may help to better understand importance and interactions between individual in vitro parameters in pulmonary delivery.

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Section: In Vitro Models To Assess Biological Processesmentioning

confidence: 99%

Biological Obstacles for Identifying In Vitro-In Vivo Correlations of Orally Inhaled Formulations

Frőhlich

2019

Pharmaceutics

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“…The dissolution profile of a dosage form constitutes an essential parameter for the bioavailability of any drug that is applied by a non-parenteral route. Factors that influence the dissolution behaviour of a drug include drug solubility, drug dose, formulation properties, drug particle properties, and the epithelial lining fluid (ELF) composition (which changes along the respiratory tract) [85]. In the lungs, the dissolution is the most significant in the small bronchioles and the alveoli, which constitute the segment where the majority of the drug absorption takes place.…”

Section: Dissolutionmentioning

confidence: 99%

“…After inhalation, the fate of the drug particles is to dissolve in the ELF present along the respiratory tract. The ELF consists of a surfactant layer and an aqueous phase [85]. According to the region of the lungs where it is situated, the lining fluid differs in composition, thickness, and volume: the trachea, bron-chi, and bronchioles are enveloped with a thick mucus gel (approximately 3 -23 μm) whereas the alveolar region is covered with a particularly thin film (approximately 0.07 μm).…”

Section: Dissolutionmentioning

confidence: 99%

Formulation and Characterization of Pulmonary Drug Delivery Systems

Magramane

Pápay

Turbucz

et al. 2019

APH

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The inhalation therapy is one of the oldest drug delivery methods known. The significance of inhalation can be understood notably through its remarkable history. The goals of this review are to explore the pulmonary drug delivery, its significant relevance and various advantageous properties, particularly due to the physiology of the lungs. The drug delivery into the lungs can be provided by several inhalation instruments presently accessible on the market such as nebulizers, MDIs, and DPIs. Supplementary devices suchlike spacers for instance are also available in order to optimize the therapy results. The efficiency of these devices depends on several parameters of the formulation used, as well as its deposition in the lungs. Therefore, this review focuses on the meticulous testing performed on both the formulation and the device carrying it in the interest of insuring safety, quality, and efficacy of the final product. Ultimately, the pulmonary drug delivery represents a substantially advantageous alternative route of administration to obtain a systemic effect as well. This review aims to the better understanding of the development of pulmonary dosage forms and its complex process which requires extensive considerations and thorough optimization.

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“…It is recognized that doses should be well dispersed and aerosol fractions defined (14). Early considerations regarding dissolution assays for orally inhaled drug products (15,16) have matured in recent years with an explosion of interest (14,17). The importance of dissolution is now being explored as a QC parameter, for establishing an IVIVC, and as an input parameter for mechanistic modelling.…”

Section: Measuring Dissolution Of Aerosol Medicinesmentioning

confidence: 99%

“…The importance of dissolution is now being explored as a QC parameter, for establishing an IVIVC, and as an input parameter for mechanistic modelling. Recent developments include the design of apparatuses for collecting aerosols and for performing dissolution studies (18), and the design of biorelevant dissolution media (17,19,20). Future needs include method standardization and the establishment of criteria for evaluating the biopharmaceutical and clinical relevance of the resulting information.…”

Section: Measuring Dissolution Of Aerosol Medicinesmentioning

confidence: 99%

Workshop Report: USP Workshop on Exploring the Science of Drug Absorption

Martinez¹,

Bhoopathy²,

Carlert³

et al. 2019

Dissolution Technol.

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In October 2018, the United States Pharmacopeia (USP) hosted a two-day workshop to explore the science of drug absorption. Experts from around the globe presented some of the challenges associated with drug product development from the perspective of the physiological attributes of the patient (human or canine) and the body site for drug activity. Included in the discussions were methods and approaches for answering complex questions, providing insights into the strengths and challenges of methods available in our biopharmaceutical tool chest. The following is a synopsis of the presentations and the highlights of the discussions that ensued. Disclaimer: This article reflects the views of the authors and should not be construed as representing the views or policies of the United States Food and Drug Administration.

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Searching for physiologically relevant in vitro dissolution techniques for orally inhaled drugs

Cited by 43 publications

References 117 publications

Biological Obstacles for Identifying In Vitro-In Vivo Correlations of Orally Inhaled Formulations

Biological Obstacles for Identifying In Vitro-In Vivo Correlations of Orally Inhaled Formulations

Formulation and Characterization of Pulmonary Drug Delivery Systems

Workshop Report: USP Workshop on Exploring the Science of Drug Absorption

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