The prevalence, burden of disease, and healthcare utilization of patients with eosinophilic granulomatosis with polyangiitis in Japan: a retrospective, descriptive cohort claims database study.

Objectives: To estimate eosinophilic granulomatosis with polyangiitis (EGPA) prevalence and disease burden in patients with newly diagnosed EGPA in Japan.

Methods: This retrospective descriptive cohort study (GSK ID: 209751, HO-18-19652) used administrative claim data from patients (aged ≤74 years) with EGPA (study period: January 1, 2005-December 31, 2017), identified from their first ICD-10 code for EGPA (index). Data were examined during the 12 months before (baseline) and 12 months following the index date (follow-up).

Enhanced biopharmaceutical effects of tranilast on experimental colitis model with use of self-micellizing solid dispersion technology.

The present study aimed to clarify the applicability of a self-micellizing solid dispersion of tranilast (SMSD/TL) to the treatment of inflammatory bowel diseases (IBD) using an experimental colitis model. SMSD/TL with several loading amounts ranging from 10 to 50% was prepared using a wet-milling system. The physicochemical properties of SMSD/TL were evaluated in terms of the dissolution behavior, morphology, and particle size distribution.

Avoidance of food effect on oral absorption profile of itraconazole by self-micellizing solid dispersion approach.

The present study was aimed to avoid pharmacokinetic transitions of itraconazole (ITZ) evoked by high-fat meal intake by employing a self-micellizing solid dispersion (SMSD) approach. The dissolution behavior of SMSD/ITZ was assessed in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). To evaluate the food effect on the oral absorption profile of ITZ, a pharmacokinetic study was conducted on orally-dosed ITZ samples in fasted and high-fat meal-fed rats.

Improved Dissolution of Dipyridamole with the Combination of pH-Modifier and Solid Dispersion Technology.

The aim of this study was to develop a pH-independent release formulation of dipyridamole (DP) by the combined use of pH-modifier technology and solid dispersion (SD) technology employing enteric polymer, Eudragit S100 (Eud). Tartaric acid (TA) was selected as an appropriate pH-modifier in terms of improving the dissolution behavior of DP under neutral conditions. Upon optimization of the ratio of TA to DP, SD of DP with Eud and TA (SD-Eud/DP/TA) was prepared by a freeze-drying method.

Protective effects of tranilast on experimental colitis in rats.

The present study aimed to verify the efficacy of tranilast (TL) for treating inflammatory bowel disease (IBD) with the use of an experimental colitis model. The experimental colitis model was prepared by intrarectal instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS; 40mg/kg) dissolved in water containing 25% ethanol. The pharmacological effects of TL after repeated oral administration were evaluated by biomarker and histological analyses, and the pharmacokinetic behavior of TL was also examined after single oral administration.

Improved oral absorption profile of itraconazole in hypochlorhydria by self-micellizing solid dispersion approach.

The present study was aimed to evaluate the applicability of a self-micellizing solid dispersion (SMSD) system of itraconazole (ITZ) with the use of Soluplus to achieve improved dissolution and stable oral absorption of ITZ under hypochlorhydric conditions. The SMSD of ITZ (SMSD/ITZ) was prepared by the freeze-drying method. Physicochemical properties of SMSD/ITZ were assessed in terms of morphology, crystallinity, particle size, thermal behavior, dissolution profile, and stability.

Strategic application of self-micellizing solid dispersion technology to respirable powder formulation of tranilast for improved therapeutic potential.

Purpose: The present study aimed to develop an inhalable self-micellizing solid dispersion of tranilast (SMSD/TL) using poly[MPC-co-BMA] to improve the therapeutic potential and safety.

Methods: The safety of poly[MPC-co-BMA] in lungs was assessed using rat lung epithelium-derived L2 cells. SMSD/TL and respirable powder of SMSD/TL (SMSD/TL-RP) were prepared using a wet milling system and jet mill, respectively.

Physicochemical stability study on cyclosporine A loaded dry-emulsion formulation with enhanced solubility.

The main purpose of the present study was to evaluate the physicochemical stability of cyclosporine A (CsA)-loaded glycerol monooleate-based dry emulsion (DE). DE formulations containing 5-25% CsA (DE5-25) were stored at 25°C/60% relative humidity for 4 weeks, and freeze-dried solid dispersion formulations containing 5-30% CsA (FD5-30) were also prepared as reference formulations. Even after the storage, no significant changes were observed in the appearance of any formulations.

Self-micellizing solid dispersion of cyclosporine A with improved dissolution and oral bioavailability.

The present study aimed to develop a self-micellizing solid dispersion (SMSD) of cyclosporine A (CsA) using an amphiphilic block copolymer, poly[MPC-co-BMA], to improve the biopharmaceutical properties of CsA. The cytotoxicity of poly[MPC-co-BMA] was assessed in rat intestinal IEC-6 cells, and the pMB was less cytotoxic than polysorbate 80, a non-ionic surfactant with a wide safety margin. SMSD/CsA was prepared using a wet-milling system, and its physicochemical properties were characterized in terms of morphology, crystallinity, dissolution, particle size distribution, and stability.

Development of novel solid dispersion of tranilast using amphiphilic block copolymer for improved oral bioavailability.

The present study aimed to develop novel solid dispersion (SD) of tranilast (TL) using amphiphilic block copolymer, poly[MPC-co-BMA] (pMB), to improve the dissolution and pharmacokinetic behavior of TL. pMB-based SD of TL (pMB-SD/TL) with drug loading of 50% (w/w) was prepared by wet-mill technology, and the physicochemical properties were characterized in terms of morphology, crystallinity, dissolution, and hygroscopicity. Powder X-ray diffraction and polarized light microscopic experiments demonstrated high crystallinity of TL in pMB-SD/TL.

Development of cyclosporine A-loaded dry-emulsion formulation using highly purified glycerol monooleate for safe inhalation therapy.

The main objective of this study was to improve the safety and oxidative stability of glycerol monooleate (GMO)-based dry-emulsion (DE) formulation containing cyclosporine A (CsA) for inhalation therapy. GMO or highly purified GMO (hpGMO) was used as surfactant for the DE formulations (GMO/DE or hpGMO/DE), the toxicological and physicochemical properties of which were characterized with a focus on oxidative stability, in vitro/in vivo toxicity, and dissolution property. Incubation of GMO at oxidation accelerating conditions for 10 days at 60°C resulted in the formation of lipid peroxides as evidenced by increased malondialdehyde (111 μmol/mg); however, hpGMO samples exhibited increase of only 20.

Inhalable powder formulation of pirfenidone with reduced phototoxic risk for treatment of pulmonary fibrosis.

Purpose: Orally-taken pirfenidone (PFD), an idiopathic pulmonary fibrosis drug, often causes severe phototoxicity. Present study aimed to develop a respirable powder formulation for PFD (PFD-RP) to minimize phototoxic risk.

Methods: Photochemical properties of PFD were examined using a reactive oxygen species (ROS) assay and photostability testing.

Inhalable sustained-release formulation of long-acting vasoactive intestinal peptide derivative alleviates acute airway inflammation.

The present study was undertaken to develop a respirable sustained-release powder (RP) formulation of long-acting VIP derivative, [Arg(15, 20, 21), Leu(17)]-VIP-GRR (IK312532), using PLGA nanospheres (NS) with the aim of improving the duration of action. NS formulation of IK312532 (IK312532/NS) was prepared by an emulsion solvent diffusion method in oil, and a mixture of the IK312532/NS and erythritol was jet-milled and mixed with lactose carrier to obtain the IK312532/NS-RP. Physicochemical properties were characterized focusing on appearance, particle size, and drug release, and in vivo pharmacological effects were assessed in antigen-sensitized rats.

Respirable dry powder formulation of bleomycin for developing a pulmonary fibrosis animal model.

The main purpose of the present study was to develop a respirable powder (RP) formulation of bleomycin (BLM) as a research tool for developing a pulmonary fibrosis animal model. The BLM-RP was prepared with a jet-milling system, the physicochemical properties of which were characterized focusing on morphology, stability, particle size distribution, and inhalation performance. Under an accelerated condition, the BLM-RP was superior to BLM solution in terms of its stability.

Physicochemical and pharmacokinetic characterization of amorphous solid dispersion of tranilast with enhanced solubility in gastric fluid and improved oral bioavailability.

In the present study, amorphous solid dispersion (ASD) formulations of tranilast (TL) with 8 hydrophilic polymers were prepared by a solvent evaporation method with the aim of improving dissolution behavior in gastric fluid and thereby enhancing oral bioavailability. The physicochemical properties were characterized with a focus on morphology, crystallinity, thermal behavior, dissolution, drug-polymer interaction, and stability. Of all TL formulations, ASD formulation with Eudragit EPO exhibited the highest improvement in dissolution behavior with a 3,000-fold increase in the first-order dissolution rate under acidic conditions (pH 1.

Inhalable dry-emulsion formulation of cyclosporine A with improved anti-inflammatory effects in experimental asthma/COPD-model rats.

The main purpose of the present study was to develop a novel respirable powder (RP) formulation of cyclosporine A (CsA) using a spray-dried O/W-emulsion (DE) system. DE formulation of CsA (DE/CsA) was prepared by spray-drying a mixture of erythritol and liquid O/W emulsion containing CsA, polyvinylpyrrolidone, and glyceryl monooleate as emulsifying agent. The DE/CsA powders were mixed with lactose carriers to obtain an RP formulation of DE/CsA (DE/CsA-RP), and its physicochemical, pharmacological, and pharmacokinetic properties were evaluated.

Formulation design and in vivo evaluation of dry powder inhalation system of new vasoactive intestinal peptide derivative ([R(15, 20, 21), L(17), A(24,25), des-N(28)]-VIP-GRR) in experimental asthma/COPD model rats.

Vasoactive intestinal peptide (VIP) has been considered as a promising drug candidate for asthma and COPD because of its potent immunomodulating and anti-inflammatory activities. Recently, our group developed a new VIP derivative, [R(15, 20, 21), L(17), A(24,25), des-N(28)]-VIP-GRR (IK312548), with improved chemical and metabolic stability. In the present study, a dry powder inhaler system of IK312548 was designed for inhalation therapy with minimal systemic side effects, the physicochemical properties of which were also evaluated with a focus on morphology, particle size distribution, inhalation performance, and peptide stability.