Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization
Abstract
Oral tadalafil (TD) proved promising in treating pediatric pulmonary arterial hypertension (PAH). However, to ensure higher efficacy and reduce the systemic side effects, targeted delivery to the lungs through nebulization was proposed as an alternative approach. This poorly soluble drug was previously dissolved in nanoemulsions (NEs). However, the formulations could not resist aqueous dilution, which precluded its dilution with saline for nebulization. Thus, the current study aimed to modify the previous systems into dilutable TD-NEs and assess their suitability for a pulmonary application. In this regard, screening of various excipients was conducted to optimize the former systems; different formulations were selected and characterized in terms of physicochemical properties, nebulization performance, stability following sterilization, and biocompatibility. Results showed that the optimal system comprised of Capmul-MCM-EP:Labrafac-lipophile (1:1) (w/w) as oil, Labrasol:Poloxamer-407 (2:1) (w/w) as surfactant mixture (Smix) and water. The optimum formulation P2TD resisted aqueous dilution, exhibited reasonable drug loading (2.45 mg/mL) and globule size (25.04 nm), acceptable pH and viscosity for pulmonary administration, and could be aerosolized using a jet nebulizer. Moreover, P2TD demonstrated stability following sterilization and a favorable safety profile confirmed by both in-vitro and in-vivo toxicity studies. These favorable findings make P2TD promising for the…
Read the paper
Related studies
- Treatment of non-metastatic castration-resistant prostate cancer: facing age-related comorbidities and drug–drug interactions
- The Efficacy of Flogofilm® in the Treatment of Chronic Bacterial Prostatitis as an Adjuvant to Antibiotic Therapy: A Randomized Prospective Trial
- Inhibition of growth and contraction in human prostate stromal cells by silencing of NUAK1 and -2, and by the presumed NUAK inhibitors HTH01-015 and WZ4003
- Effectiveness and Safety of a New Nutrient Fixed Combination Containing Pollen Extract Plus Teupolioside, in the Management of LUTS in Patients with Benign Prostatic Hypertrophy: A Pilot Study
- Extract from Cucurbita pepo improves BPH symptoms without affecting sexual function: a 24-month noninterventional study
- Aquablation vs. holmium laser enucleation of the prostate for benign prostatic hyperplasia: a 150-patients prospective comparative multicenter study
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.