Risk Management for Materials and Components Used in Orally Inhaled and Nasal Drug Products

Stults, Cheryl L. M.; Reckzuegel, Gaby; Bailey, Arthur W.; Petersen, Jonathan; Dick, Lisa; Feinberg, Thomas N.; Feilden, Andrew; Miller, Sara; Connors, James J.; Nagao, Lee M.

doi:10.1007/s11095-015-1770-7

Cited by 10 publications

(9 citation statements)

References 3 publications

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“…Inhalation with nebulized liquid- or powder-based aerosols fails to target the olfactory cleft efficiently [ 151 ]. Therefore, some devices were developed to enable N2B drug delivery.…”

Section: Formulations Dosage Forms and Medical Devices For Intranmentioning

confidence: 99%

Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa

2018

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The blood-brain barrier and the blood-cerebrospinal fluid barrier are major obstacles in central nervous system (CNS) drug delivery, since they block most molecules from entering the brain. Alternative drug delivery routes like intraparenchymal or intrathecal are invasive methods with a remaining risk of infections. In contrast, nose-to-brain delivery is a minimally invasive drug administration pathway, which bypasses the blood-brain barrier as the drug is directed from the nasal cavity to the brain. In particular, the skull base located at the roof of the nasal cavity is in close vicinity to the CNS. This area is covered with olfactory mucosa. To design and tailor suitable formulations for nose-to-brain drug delivery, the architecture, structure and physico-chemical characteristics of the mucosa are important criteria. Hence, here we review the state-of-the-art knowledge about the characteristics of the nasal and, in particular, the olfactory mucosa needed for a rational design of intranasal formulations and dosage forms. Also, the information is suitable for the development of systemic or local intranasal drug delivery as well as for intranasal vaccinations.

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“…Inhalation with nebulized liquid- or powder-based aerosols fails to target the olfactory cleft efficiently [ 151 ]. Therefore, some devices were developed to enable N2B drug delivery.…”

Section: Formulations Dosage Forms and Medical Devices For Intranmentioning

confidence: 99%

Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa

2018

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“…However, the impact of insoluble polymers on the maximum achievable concentration (the amorphous “solubility”) of a drug is poorly explored, and there is a substantial knowledge gap in terms of understanding the extent of supersaturation reduction by mixing with insoluble polymers. Elucidating the maximum achievable drug release from amorphous drug delivery systems containing insoluble polymers is important in the context of suspension stability[23], in terms of providing fundamental information about the extent of thermodynamic stabilization of the drug by the polymer, as well for insights into potential in vivo performance.…”

Section: Introductionmentioning

confidence: 99%

Tailoring supersaturation from amorphous solid dispersions

Taylor

2018

Journal of Controlled Release

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The maximum achievable concentration of a drug in solution is dictated by the chemical potential of the solid form. Because an amorphous solid has a higher chemical potential than the corresponding crystal form, in the absence of phase transformations, a higher transient solubility is expected. However, the chemical potential of an amorphous drug can be reduced by mixing with another component. Therefore, upon mixing with a polymer to form an amorphous solid dispersion (ASD), the maximum solution concentration achieved can be potentially altered, in particular if the polymer is poorly soluble in the dissolution medium. Such changes in the chemical potential of the drug may be a critical factor in determining the maximum achievable solution concentration, and could alter the crystallization driving force of the drug. Therefore, the aim of this study was to gain insights into the impact of poorly soluble polymers on the "amorphous solubility" of drugs formulated as amorphous solid dispersions. Lopinavir was selected as a model drug with a low crystallization tendency, enabling determination of the amorphous solubility as a function of ASD composition. Model polymers included cellulose acetate (CA), CA phthalate (CAP), ethylcellulose (EC), Eudragit® RL PO (EUD), hydroxypropylmethylcellulose (HPMC), HPMC acetate succinate (HPMCAS), and HPMC phthalate (HPMCP). The "amorphous solubility" of the drug alone was determined and then the changes in maximum achievable concentration were measured as a function of drug loading. Drug-polymer interactions were characterized using infrared spectroscopy (IR), differential scanning calorimetry (DSC) and moisture sorption analysis. The results showed that the maximum achievable concentration ("amorphous solubility") of lopinavir varied with the extent of drug-polymer interactions, as well as the drug weight fraction in the ASD. This information is of great value when evaluating the maximum achievable concentration of amorphous systems formulated with pH responsive polymers, and should contribute to a broader understanding of drug phase behavior in the context of ASDs.

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“…Phototherapies, such as photodynamic (PDT) and photothermal (PTT) therapies, have emerged as promising alternatives owing to their specificity, low systemic toxicity, and low invasiveness in comparison with other therapies [ 4 – 8 ]. In addition, it has been shown that these therapies can be used in combination with other available therapies, as well as with targeted drug delivery systems, which can be more efficient in overcoming tumors [ 9 , 10 ]. To be effective, PDT needs three components, oxygen (O 2 ), a photosensitizer (PS) and light of specific wavelength.…”

Section: Introductionmentioning

confidence: 99%

Nanographene oxide-methylene blue as phototherapies platform for breast tumor ablation and metastasis prevention in a syngeneic orthotopic murine model

et al. 2018

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Background: In the photodynamic therapy (PDT), the photosensitizer absorbs light and transfers the energy of the excited state to the oxygen in the cell environment producing reactive oxygen species (ROS), that in its turn, may cause cell damage. In the photothermal therapy (PTT), light also is responsible for activating the photothermal agent, which converts the absorbed energy in heat. Graphene oxide is a carbon-based material that presents photothermal activity. Its physical properties allow the association with the photosensitizer methylene blue and consequently the production of ROS when submitted to light irradiation. Therefore, the association between nanographene oxide and methylene blue could represent a strategy to enhance therapeutic actions. In this work, we report the nanographene oxide-methylene blue platform (NanoGO-MB) used to promote tumor ablation in combination with photodynamic and photothermal therapies against a syngeneic orthotopic murine breast cancer model. Results:In vitro, NanoGO-MB presented 50% of the reactive oxygen species production compared to the free MB after LED light irradiation, and a temperature increase of ~ 40 °C followed by laser irradiation. On cells, the ROS production by the nanoplatform displayed higher values in tumor than normal cells. In vivo assays demonstrated a synergistic effect obtained by the combined PDT/PTT therapies using NanoGO-MB, which promoted complete tumor ablation in 5/5 animals. Up to 30 days after the last treatment, there was no tumor regrowth compared with only PDT or PTT groups, which displayed tumoral bioluminescence 63-fold higher than the combined treatment group. Histological studies confirmed that the combined therapies were able to prevent tumor regrowth and liver, lung and spleen metastasis. In addition, low systemic toxicity was observed in pathologic examinations of liver, spleen, lungs, and kidneys. Conclusions:The treatment with combined PDT/PTT therapies using NanoGO-MB induced more toxicity on breast carcinoma cells than on normal cells. In vivo, the combined therapies promoted complete tumor ablation and metastasis prevention while only PDT or PTT were unable to stop tumor development. The results show the potential of NanoGO-MB in combination with the phototherapies in the treatment of the breast cancer and metastasis prevention.

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Risk Management for Materials and Components Used in Orally Inhaled and Nasal Drug Products

Cited by 10 publications

References 3 publications

Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa

Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa

Tailoring supersaturation from amorphous solid dispersions

Nanographene oxide-methylene blue as phototherapies platform for breast tumor ablation and metastasis prevention in a syngeneic orthotopic murine model

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