Transdermal iontophoresis of dexamethasone sodium phosphate in vitro and in vivo: Effect of experimental parameters and skin type on drug stability and transport kinetics

2010 ◽  
Vol 75 (2) ◽  
pp. 173-178 ◽  
Author(s):  
J. Cázares-Delgadillo ◽  
C. Balaguer-Fernández ◽  
A. Calatayud-Pascual ◽  
A. Ganem-Rondero ◽  
D. Quintanar-Guerrero ◽  
...  
Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 161
Author(s):  
Glenn Lemmens ◽  
Arno Van Camp ◽  
Stephanie Kourula ◽  
Tim Vanuytsel ◽  
Patrick Augustijns

The increasing prevalence of colonic diseases calls for a better understanding of the various colonic drug absorption barriers of colon-targeted formulations, and for reliable in vitro tools that accurately predict local drug disposition. In vivo relevant incubation conditions have been shown to better capture the composition of the limited colonic fluid and have resulted in relevant degradation and dissolution kinetics of drugs and formulations. Furthermore, drug hurdles such as efflux transporters and metabolising enzymes, and the presence of mucus and microbiome are slowly integrated into drug stability- and permeation assays. Traditionally, the well characterized Caco-2 cell line and the Ussing chamber technique are used to assess the absorption characteristics of small drug molecules. Recently, various stem cell-derived intestinal systems have emerged, closely mimicking epithelial physiology. Models that can assess microbiome-mediated drug metabolism or enable coculturing of gut microbiome with epithelial cells are also increasingly explored. Here we provide a comprehensive overview of the colonic physiology in relation to drug absorption, and review colon-targeting formulation strategies and in vitro tools to characterize colonic drug disposition.


Author(s):  
Graciela Lizeth Pérez-González ◽  
Luis Jesús Villarreal-Gómez ◽  
Amelia Olivas-Sarabia ◽  
Ricardo Valdez ◽  
José Manuel Cornejo-Bravo

Toxins ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 426
Author(s):  
Yu-Ju Kuo ◽  
Yao Tsung Chang ◽  
Ching-Hu Chung ◽  
Woei-Jer Chuang ◽  
Tur-Fu Huang

Polymer polyethylene glycol (PEG), or PEGylation of polypeptides improves protein drug stability by decreasing degradation and reducing renal clearance. To produce a pharmaceutical disintegrin derivative, the N-terminal PEGylation technique was used to modify the disintegrin derivative [KGDRR]trimucrin for favorable safety, pharmacokinetic profiles, and antithrombotic efficacy. We compared intact [KGDRR]trimucrin (RR) and PEGylated KGDRR (PEG-RR) by in vitro and in vivo systems for their antithrombotic activities. The activity of platelet aggregation inhibition and the bleeding tendency side effect were also investigated. PEG-RR exhibited optimal potency in inhibiting platelet aggregation of human/mouse platelet-rich plasma activated by collagen or ADP with a lower IC50 than the intact derivative RR. In the illumination-induced mesenteric venous thrombosis model, RR and PEG-RR efficaciously prevented occlusive thrombosis in a dose-dependent manner. In rotational thromboelastometry assay, PEG-RR did not induce hypocoagulation in human whole blood even given at a higher concentration (30 μg/mL), while RR slightly prolonged clotting time. However, RR and PEG-RR were not associated with severe thrombocytopenia or bleeding in FcγRIIa-transgenic mice at equally efficacious antithrombotic dosages. We also found the in vivo half-life of PEGylation was longer than RR (RR: 15.65 h vs. PEG-RR: 20.45 h). In conclusion, injectable PEG-RR with prolonged half-life and decreased bleeding risk is a safer anti-thrombotic agent for long-acting treatment of thrombus diseases.


2010 ◽  
Vol 39 (5) ◽  
pp. 387-393 ◽  
Author(s):  
Jennyfer Cázares-Delgadillo ◽  
Adriana Ganem-Rondero ◽  
David Quintanar-Guerrero ◽  
Alicia C. López-Castellano ◽  
Virginia Merino ◽  
...  

2020 ◽  
Author(s):  
Hitomi Amano ◽  
Yoshiro Kitagawa ◽  
Taichiro Muto ◽  
Akihisa Okumura ◽  
Hideyuki Iwayama

Abstract BackgroundAnaphylaxis is a severe systemic allergic reaction. Glucocorticoids rarely induce anaphylaxis. Determination of allergens includes the in vivo skin prick test (SPT) and intradermal skin test (IDST) and the in vitro basophil activation test (BAT). However, the usefulness of BAT in determining drug allergens has not been adequately studied.Case presentation A 10-year-old boy was admitted to our hospital because of fever and arthralgia for 2 weeks. He had not been treated with glucocorticoids. According to the laboratory tests and imaging studies, he was suspected to have bacterial myositis and was treated with ceftriaxone. However, his symptoms persisted for more than 2 weeks. With a suspicion of autoinflammatory arthritis, we planned methylprednisolone (mPSL) sodium succinate (MPS) during pulse therapy (30 mg/kg). Fifteen minutes after the injection of mPSL, he had wheezing and generalized wheal formation with decreased oxygenation. The administration of mPSL was discontinued because anaphylaxis was suspected. Thirty minutes after the administration of oxygen and oral olopatadine, the anaphylactic symptoms resolved. One month after discharge, SPT, IDST, and BAT were performed under the administration of oral prednisolone. The SPTs for MPS, hydrocortisone sodium succinate (HCS) and prednisolone sodium succinate (PSS) were negative. The IDST for MPS was positive. Moreover, the IDSTs for HCS and PSS were positive, whereas those for dexamethasone sodium phosphate and betamethasone sodium phosphate were negative. The BAT for MPS was negative at 1.0% and 1.9% after an incubation time of 1 hour and 24 hours, respectively, although the BAT for histamine as positive control was 60.4% and 18.3% after an incubation time of 1 hour and 24 hours, respectively. The BATs for HCS and PSS were negative. Therefore, we diagnosed as anaphylaxis secondary to the succinate ester in MPS.ConclusionsIn this case, IDST was useful for the diagnosis of MPS-induced anaphylaxis, whereas BAT was negative. This highlighted the need to choose the appropriate procedure in the diagnosis of steroid-induced anaphylaxis. The results in our patient suggested that BAT may be considered when IDST and SPT are negative. Further studies are necessary to clarify the diagnostic strategy for steroid-induced anaphylaxis.


1970 ◽  
Vol 2 (1) ◽  
pp. 56-60
Author(s):  
Nazia Zaman ◽  
Md Mesbah Uddin Talukder ◽  
Tasnuva Haque ◽  
Md Khairul Alam ◽  
Kanij Fatema

The present study was carried out to develop biodegradable intrascleral implants of Dexamethasone Sodium Phosphate and to evaluate the release pattern of the drug from the prepared implants. Intrascleral implants were prepared by using biodegradable polymer L-PLA (m.wt. 61,200 Da). Sodium chloride (NaCl), gelatin and glycerol monostearate (GMS) were used in various formulations to observe the effects of these additives on the release of Dexamethasone Sodium Phosphate from the prepared L-PLA based intrascleral implants. Five different formulations were prepared for this study and were coded as FD-1 (10%drug+L-PLA), FD-2 (20%drug+L-PLA), FD-3 (10%drug+L-PLA+5%NaCl), FD-4 (10%drug+L-PLA +5%Gelatin) and FD-5 (10%drug+L-PLA+10% GMS). Discs were prepared and made into appropriate shape before submerging into the buffer solution of pH 7.4 in different vials. The in vitro release profile of Dexamethasone Sodium Phosphate from the implants showed a biphasic release pattern with an initial burst followed by a diffusive phase. It was observed that FD-1 and FD-2 showed 19.63% and 29.87% release on the first day and 24.22% and 38.5% release respectively at day 30. The drug loading of FD-1 and FD-2 was 10% and 20% respectively. Among FD-3, FD-4 and FD-5; FD-3 showed highest release (32.1%) at day 30 in which 5% NaCl was used. FD-4 showed 27.45% release at day 30 where gelatin, a hydrophilic agent was used and FD-5 containing GMS, a lipid material, was found to be most retarding (19.22% at day 30). The results of the dissolution study provide an idea that L-PLA may be successfully used for the preparation of biodegradable intrascleral implant of Dexamethasone Sodium Phosphate. Key words: Dexamethasone Sodium Phosphate; Bioidegradable polymer; Intrascleral implants. DOI: 10.3329/sjps.v2i1.5817Stamford Journal of Pharmaceutical Sciences Vol.2(1) 2009: 56-60


2018 ◽  
Vol 32 (2) ◽  
pp. 102-110 ◽  
Author(s):  
Shodeinde A. Coker ◽  
Zbigniew M. Szczepiorkowski ◽  
Alan H. Siegel ◽  
Antonio Ferrari ◽  
Giovanni Mambrini ◽  
...  

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