betadex and Candidiasis

The development of vaginal medications, especially antifungal medications, requires that the drug is solubilized as well as retained at or near the mucosa for sufficient periods of time to ensure adequate bioavailability. Itraconazole is a broad-spectrum antifungal agent, which has been used for some time orally and intravenously but for which a vaginal formulation has not yet been developed. We present here a novel itraconazole formulation intended for vaginal use based on hydroxypropyl-beta-cyclodextrin (HPbetaCD), a functional excipient that increases drug solubility and generates a mucoadhesive system in the presence of other ingredients. An aqueous phase was prepared by solubilizing itraconazole with HCl in the presence of propylene glycol and then adding an aqueous solution of HPbetaCD. After pH adjustment, the itraconazole/HPbetaCD solution was added to the oil phase (paraffin oil, trihydroxystearate, and cetyl dimethicon copolyol) and the desired cream containing 1%, 2%, and 2.5% drug obtained by homogenization. Primary irritation studies and subchronic toxicity studies using a rabbit vaginal model indicated that the formulation was safe, well tolerated, and retained in the vaginal space. Clinical investigations indicated that application of 5 g of a 2% cream was very well tolerated and itraconazole was not systemically absorbed. Additional studies in women found that the itraconazole cream was highly effective in reducing or eliminating fungal cultures with few adverse effects. These studies suggested that an HPbetaCD-based, emulsified wax cream formulation was a useful and effective dosage form for treating vaginal candidiasis.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Antifungal Agents; beta-Cyclodextrins; Biological Availability; Candida albicans; Candidiasis; Cyclodextrins; Dosage Forms; Drug Evaluation, Preclinical; Drug Stability; Female; Humans; Itraconazole; Rabbits; Solubility; Solutions; Vaginal Creams, Foams, and Jellies; Vaginal Diseases

Bacterial pneumonia is a common cause of death worldwide. Tea tree oil (TTO) is a potent antimicrobial natural product, which is formulated in dry powder inhalers (DPIs) for the treatment of fungal and bacterial pneumonia.. Tea tree oil-β-cyclodextrin inclusion complexes (TTO-β-CD) were prepared and characterized. Aerodynamic properties of TTO-β-CD powders were measured. The rat models of fungal (Candida albicans) and bacterial (Acinetobacter baumannii) pneumonia were prepared. Saline, TTO, TTO-β-CD and the positive drug (fluconazole or penicillin) were directly delivered to the rat lungs. Pathological and biological assays were conducted.. Tea tree oil-β-CD powders had an appropriate aerodynamic diameter of 5.59 μm and the fine particle fraction of 51.22%, suitable for pulmonary delivery. TTO-β-CD showed higher and similar antipneumonic effects on the rat models than fluconazole and penicillin, respectively. The effects of TTO-β-CD were higher than TTO alone. The antipneumonic mechanisms involved blocking the recruitment of leucocytes and neutrophils, eliminating the microbes, downregulating pro-inflammatory cytokines (including tumour necrosis factor-α, interleukin-1β and interleukin-6), suppressing cyclooxygenase 2 expression, and further reducing lung injury.. Inhaled TTO-β-CD powders have the advantages of portability, high stability, self-administration, high lung deposition and good antipneumonic effect. It is a promising DPI for the treatment of fungal and bacterial pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Antifungal Agents; beta-Cyclodextrins; Candida albicans; Candidiasis; Disease Models, Animal; Drug Delivery Systems; Fluconazole; Lung; Male; Penicillins; Pneumonia; Pneumonia, Bacterial; Rats; Rats, Sprague-Dawley; Tea Tree Oil; Tissue Distribution