A levodopa dry powder inhaler for the treatment of Parkinson’s disease patients in off periods

Luinstra, Marianne; Grasmeijer, Floris; Hagedoorn, Paul; Moes, Jan Reindert; Frijlink, Henderik W.; Boer, Anne H. de

doi:10.1016/j.ejpb.2015.10.003

Cited by 35 publications

(19 citation statements)

References 22 publications

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“…How this exactly translates to the results found in this study is not known and is an interesting issue to consider for future research. So, while l -leucine is known for lubrication [20,23], and has been successfully used in other milled formulations [24], it does not result in a suitable formulation here.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Formulation of Isoniazid for High-Dose Dry Powder Inhalation

et al. 2019

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Tuberculosis is a major health problem and remains one of the main causes of mortality. In recent years, there has been an increased interest in the pulmonary delivery of antibiotics to treat tuberculosis. Isoniazid is one of these antibiotics. In this study, we aimed to characterize isoniazid and formulate it into a dry powder for pulmonary administration with little or no excipient, and for use in the disposable Twincer® inhaler. Isoniazid was jet milled and spray dried with and without the excipient l-leucine. Physiochemical characterization showed that isoniazid has a low Tg of −3.99 ± 0.18 °C and starts to sublimate around 80 °C. Milling isoniazid with and without excipients did not result in a suitable formulation, as it resulted in a low and highly variable fine particle fraction. Spray drying pure isoniazid resulted in particles too large for pulmonary administration. The addition of 5% l-leucine resulted in a fraction <5 µm = 89.61% ± 1.77% from spray drying, which dispersed well from the Twincer®. However, storage stability was poor at higher relative humidity, which likely results from dissolution-crystallization. Therefore, follow up research is needed to further optimize this spray dried formulation.

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Section: Discussionmentioning

confidence: 99%

Characterization and Formulation of Isoniazid for High-Dose Dry Powder Inhalation

et al. 2019

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“…In addition, it has been proven that in the presence of antioxidants, L-Dopa can be protected from oxidation. Therefore, we planned to obtain information about the stability of L-Dopa in the presence of ascorbic acid in the body and during the validation and formulation studies (3,18,22). 0.4 mg/mL L-Dopa containing stock solutions were prepared with pH 4.5 and pH 7.4 buffered solutions.…”

Section: Stabilitymentioning

confidence: 99%

Evaluatıon Of Release Of L-DOPA From PLGA Nanopartıcles Wıth Dıfferent In Vıtro Relase Methods By An Optımızed HPLC Method

Arısoy¹,

Sayiner²,

Çomoğlu³

2020

Bezmialem Science

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Amaç: Farmasötik alanda çözünme hızı testleri, ilaç ürün performansını karakterize etmek için önemli parametrelerdendir. Üretim sürecinden sonra ürün kalitesini ve performansını sağlamak için, formülasyondaki değişiklikler, yeni formülasyonların geliştirilmesi sırasında çözünme testleriyle değerlendirilebilir. Yöntemler: Bu çalışmada, poli (D, L-laktik-ko-glikolik asit) (PLGA) nanopartiküllerinden salınan L-Dopa miktarının belirlenmesi için Yüksek Basnıçlı Sıvı Kromatografisi (HPLC) yöntemi geliştirilmiş ve onaylanmıştır. 280 nm dalga boyunda hareketli faz olarak % 0.05 trifloroasetik asit (5:95, h/ h) içeren asetonitril-su kullanılarak, ters fazlı C18 kolonu ile kromatografik ayırma yapılmıştır. Geliştirilen yöntem, özgünlüğü, doğrusallığı, doğruluğu ve kesinliği için ICH kurallarına göre doğrulanmıştır. Bulgular: Yöntemin 1.25-40 µg / mL konsantrasyon aralığında doğrusal (r2 ≥ 0,995) olduğu gösterilmiştir. Ortalama % geri kazanım, % 102.59-% 98.70 arasında olup, gerçek değer ile tespit edilen değer arasında bir korelasyon olduğu belirlenmiştir. Antioksidan ilavesiyle çözelti stabilitesi sağlanmıştır. Analitik yöntemin nanopartiküllerden salınan L-Dopa'nın değerlendirilmesi için uygun olduğu gösterilmiştir. Örnek ve ayırma (SS) ve diyaliz membranı (DM) yöntemleri kullanılarak in vitro salım çalışmaları yapılmıştır. SS ve DM yöntemlerinin karşılaştırılmasında farklılık (ƒ1) ve benzerlik (ƒ2) faktörleri kullanılmıştır. L-Dopa salım kinetiğindeki fark her iki yöntem için de anlamlı bulunmamıştır (ƒ1 < 15 ve ƒ2 > 50). Objective: Dissolution tests have emerged in the pharmaceutical field as a very important tool to characterize drug product performance. To assure product quality and performance after the manufacturing process, changes in the formulation can be assessed through dissolution tests during the development of new formulations. Methods: In this study, a simple High Performance Liquid Chromatography (HPLC) method was developed and validated for the quantitation of release of L-Dopa from poly (D, L-lactic-coglycolic acid) (PLGA) nanoparticles. Chromatographic separation was done with a reversed-phase C18 column, using acetonitrilewater containing 0,05% trifluoroacetic acid (5:95, v/v) as a mobile phase at a wavelength of 280 nm. The developed method was validated according to ICH guidelines for its specificity, linearity, accuracy, and precision. Results:The method was shown to be linear (r2 ≥ 0.995) over the concentration range of 1,25-40 µg / mL. The mean % recoveries were in between, 102.59 %-98.70 % indicating an agreement between the true value and the detected value. Solution stability was guaranteed with antioxidant addition. The analytical method was shown to be suitable for the evaluation of L-Dopa which is released from nanoparticles. In vitro release studies were performed using sample and separate (SS), and dialysis membrane (DM) methods. Difference (ƒ1) and similarity (ƒ2) factors were used in the comparison of the SS and DM methods. The difference in the

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“…35 To be able to target macrophages, the particles made must be ensured to be able to enter the respiratory tract particularly into the inner lungs, especially on the alveoli. Besides by synchronizing with the milling, ball milling, and spray drying techniques, 36,37 to improve the aerosolization properties of a given particulate system in the form of dry powder inhalation (DPI), it also uses other excipients such as lactose and mannose with certain particle sizes. Du et al 38 conducted an evaluation of the effects of lactose and granule lactose administration within a certain size to the aerosilization of salbutamol DPI.…”

Section: Properties Of Aerosolizationmentioning

confidence: 99%

Microsphere-Based Drug Delivery to Alveolar Macrophages - a Review

2020

TJNPR

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Lungs have a complex but coordinated system to eliminate inhaled pathogenic and pollutant particles. Pulmonary contact with pathogenic particles has the potential to cause respiratory disturbances, so the process of eliminating foreign particles must be ensured to continue functioning normally. Pulmonary delivery system becomes the choice of drug delivery, for example in the provision of inhaled antibiotics aimed at several diseases such as tuberculosis and pneumonia. This delivery route is also intended for the treatment of pulmonary hypertension 1 and the administration of paclitaxel and doxurobicin in the treatment of lung cancer. 2 In several studies that have been carried out, inhalation delivery system is also intended to have a systemic effect, for example insulin delivery, 3 delivery of antinerve growth factor hormone, 4 and antithrombotic therapy. 5 Lungs' natural defense mechanism to fight pollutants and potentially pathogenic particles is a complex system and involves several processes such as mucociliary cleansing, the release of anti-pathogenic endogenous proteins, and the presence of leukocyte responses that occur in the lungs. 6 Alveolar macrophages are the first defense

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A levodopa dry powder inhaler for the treatment of Parkinson’s disease patients in off periods

Cited by 35 publications

References 22 publications

Characterization and Formulation of Isoniazid for High-Dose Dry Powder Inhalation

Characterization and Formulation of Isoniazid for High-Dose Dry Powder Inhalation

Evaluatıon Of Release Of L-DOPA From PLGA Nanopartıcles Wıth Dıfferent In Vıtro Relase Methods By An Optımızed HPLC Method

Microsphere-Based Drug Delivery to Alveolar Macrophages - a Review

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