Characterization of a cyclosporine solid dispersion for inhalation

For lung transplant patients, a respirable, inulin-based solid dispersion containing cyclosporine A (CsA) has been developed. The solid dispersions were prepared by spray freezedrying. The solid dispersion was characterized by water vapor uptake, specific surface area analysis, and particle size analysis. Furthermore, the mode of inclusion of CsA in the dispersion was investigated with Fourier transform infrared spectroscopy. Finally, the dissolution behavior was determined and the aerosol that was formed by the powder was characterized. The powder had large specific surface areas (∼160 m2). The water vapor uptake was dependent linearly on the drug load. The type of solid dispersion was a combination of a solid solution and solid suspension. At a 10% drug load, 55% of the CsA in the powder was in the form of a solid solution and 45% as solid suspension. At 50% drug load, the powder contained 90% of CsA as solid suspension. The powder showed excellent dispersion characteristics as shown by the high emitted fraction (95%), respirable fraction (75%), and fine-particle fraction (50%). The solid dispersions consisted of relatively large (x50≈7 μm), but low-density particles (ρ≈0.2 g/cm3). The solid dispersions dissolved faster than the physical mixture, and inulin dissolved faster than CsA. The spray freeze-drying with inulin increased the specific surface area and wettability of CsA. In conclusion, the developed powder seems suitable for inhalation in the local treatment of lung transplant patients

Development of a core outcome domain set for clinical research on capillary malformations (the COSCAM project)

BACKGROUND: Due to a large variety in treatment outcomes reported in therapeutic trials and lacking patient‐relevant outcomes, it is hard to adequately compare and improve current therapies for patients with capillary malformations (CMs). The Core Outcome Set for Capillary Malformations (COSCAM) project aims to develop a core outcome set (COS) for use in future CM trials, in which we will first develop a core outcome (sub)domain set (CDS). Here, we describe the methods for the development of a CDS and present the results of the first development stage. METHODS: The COSCAM project is carried out according to the recommendations of the Cochrane Skin Core OUtcomes Set INitiative (CS‐COUSIN) and the Core Outcome Measures in Effectiveness Trials (COMET) initiative. During the first stage, we identified all potentially relevant outcome subdomains based on a systematic review, two focus group sessions and input from patient representatives of Dutch patient organizations and the COSCAM‐founding group. In stage two, we will present the subdomains in a three‐round e‐Delphi study and online consensus meeting, in which CM patients, parents/caregivers and CM experts worldwide rate the importance of the proposed subdomains, hereby finalizing the core outcome (sub)domains of the CDS. RESULTS: A total of 67 potential outcome subdomains were included; sixteen were previously used in the literature, 20 were proposed by Dutch patients and their parents/caregivers (n = 13) in focus group sessions and 38 were suggested by the experts of the COSCAM‐founding group. Seven were excluded because of overlap. CONCLUSION: The final CDS may serve as a minimum standard in future CM trials, thereby facilitating adequate comparison of treatment outcomes. After this CDS development, we will select appropriate outcome measurement instruments to measure the core outcome subdomains

Vascular Laser and Light Treatments

This chapter provides an overview of vascular targeting light treatments applied to treatment of commonly encountered cutaneous vascular lesions, specifically port wine birthmarks (PWBs), infantile hemangiomas (IHs), and telangiectasias. Evidence-based recommendations are provided regarding light-based treatment effectiveness, preoperative evaluation, treatment techniques, safety, and postoperative management. We also discuss device and drug combinations which have been utilized including photodynamic therapy or laser in combination with antiangiogenic agents for PWBs and beta-blockers with lasers for IHs. This chapter provides a practical, concise, and evidence-based guide for the utilization of vascular-specific laser treatments available today

Enhanced Solubility, Stability, and Transcorneal Permeability of Delta-8-Tetrahydrocannabinol in the Presence of Cyclodextrins

The purpose of this study was to investigate the effect of cyclodextrins (CDs) on aqueous solubility, stability, and in vitro corneal permeability of delta-8-tetrahydrocannabinol (Δ8-THC). Phase solubility of Δ8-THC was studied in the presence of 2-hydroxypropyl-β-cyclodextrin (HPβCD), randomly methylated-β-cyclodextrin (RMβCD) and sulfobutyl ether-β-cyclodextrin sodium salt (SβCD). Stability of Δ8-THC in 5% w/v aqueous CD solutions, as a function of pH, was studied following standard protocols. In vitro corneal permeation of Δ8-THC (with and without CDs) across excised rabbit cornea was also determined. Phase-solubility profile of Δ8-THC in the presence of both HPβCD and RMβCD was of the AP type, whereas, with SβCD an AL type was apparent. Aqueous solubility of Δ8-THC increased to 1.65, 2.4, and 0.64 mg/mL in the presence of 25% w/v HPβCD, RMβCD, and SβCD, respectively. Significant degradation of Δ8-THC was not observed within the study period at the pH values studied, except for at pH 1.2. Transcorneal permeation of Δ8-THC was dramatically improved in the presence of CDs. The results demonstrate that CDs significantly increase aqueous solubility, stability, and transcorneal permeation of Δ8-THC. Thus, topical ophthalmic formulations containing Δ8-THC and modified beta CDs may show markedly improved ocular bioavailability