Browsing by Subject "Sustained release"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Dry powder antibiotics for inhaled anti-tuberculosis therapy(2010-12) Son, Yoen Ju; McConville, Jason Thomas; McGinity, James W.; Williams, Robert O.; Wiederhold, Nathan; Roy, KrishnenduThe aim of this research was to develop and fully investigate a novel method of antibiotic drug delivery to the lung that will address problems with current therapeutic regimens for treatment of airway infections. To demonstrate the performance of prepared formulations, the design of suitable characterization methods were also aimed. A novel dissolution method for evaluating the in vitro dissolution behavior of inhalation formulations was developed. The membrane holder was designed to enclose previously air-classified formulations so that they could be uniformly tested in the dissolution apparatus. Dissolution procedures, the apparatus, the dose collection, the medium, and test conditions were developed and the dissolution behaviors of test compounds were evaluated by experimental and mathematical analysis. It was proved that the aerodynamic separation of formulation prior to dissolution assessment have a significant influence on the dissolution profiles. The optimized test method using the membrane holder was applied to evaluate in vitro dissolution profiles of the manufactured formulations of rifampicin (RF). The carrier/excipient-free RF dry powder formulation was investigated. The rifampicin dihydrate (RFDH) powders having MMAD of 2.2 um were prepared using a simple recrystallization process. The RFDH powders have a thin flaky structure, and this unique morphology provides improved aerosolization properties at maximal API loading. The manufactured RFDH formulation showed 80% drug release within 2 hours. To retard the release rate of RF, the prepared RFDH crystals were coated with hydrophobic polymer, PLA or PLGA, using spray-dryer equipped with multi-channel spray nozzles. The multi-channel spray nozzle used in this study has two separate nozzles for aqueous solution and one for gas fluid. The RFDH crystals and the coating solutions were sprayed through the two separate liquid nozzles at the same time. The coated RFDH formulations were prepared using multi-channel spray nozzles. The coated formulations contained at least 50% w/w of RF with no change of their flaky morphology. The initial RF release was lowered by coating; the lowest initial RF release was observed from the coated powders with PLA polymer as 32% among the coated formulations. Overall, the 80% of RF was released within 8 hours. The RFDH and coated RFDH formulations delivered via the pulmonary route would be anticipated to provide higher local (lung) drug concentrations than that of orally delivered powders. Particularly, the coated RFDH powders deposited in the alveolar region may prolong the drug residence time in the site of infections. Additionally, it was proved that the RFDH and coated RFDH formulations provided much better stability than the amorphous RF.Item Sustained release drug delivery applications of poly(urethanes)(2020-01-31) Lowinger, Michael Brian; Zhang, Feng, Ph. D.; Williams, Robert O., III, 1956-Patient adherence to drug therapies remains an obstacle to realizing their full therapeutic benefit. Sustained release formulations may decrease frequency of administration, potentially improving patient adherence. Implants may decrease dosing frequency to once every 5 years. However, most polymers used today are hydrophobic, limiting drug properties suitable for development. Thermoplastic poly(urethanes) (TPUs) form pores upon hydration, offering a different release mechanism. We sought to assess the range of drug diffusion rates achieved by varying hydrophilic-to-hydrophobic TPU ratio compared with poly(ethylene-co-vinyl acetate) (EVA) crystallinity; investigate the effect of drug physicochemical properties on permeability through membranes of varying TPU composition; visualize microstructural changes to the membrane across the TPU composition range; and characterize the membrane microstructure. Emtricitabine exhibited a >200-fold broader permeability range across the TPU blends than EVA grades. Varying hydrophilic content of the TPU mixture between 0- 25% (w/w) led to a negligible permeability change, whereas a >100-fold permeability change occurred between 50-55% (w/w). We observed a correlation between drug hydrophobicity and its permeability through hydrophobic-rich TPU. Conversely, drugs diffused through hydrophilic-rich TPU at similar rates, regardless of properties. Imaging revealed significant microstructure differences between hydrophobic-rich and hydrophilic-rich TPU, supporting that hydrophilic polymer domains form a continuous network above 55% (w/w) hydrophilic TPU. The large hydrophilic TPU equivalent pore radius suggests that it may modify the release of small molecular weight drugs and macromolecules. Gastroretentive formulations may reduce dosing frequency of medications otherwise taken up to 5 times per day. Acyclovir is a short half-life drug with poor colonic absorption, and conventional controlled release formulations are unable to decrease dosing frequency. We developed a modified-release acyclovir matrix tablet and surrounded it with a hydrophilic poly(urethane) layer. When hydrated, the poly(urethane) swells to a size near to or beyond the relaxed pylorus diameter, without affecting drug release rate. We demonstrated that the formulation is retained in the stomach for extended durations as it slowly releases drug, allowing for similar AUC but delayed t [subscript max] relative to a control tablet. Unlike other gastroretentive formulations, this design decouples drug release rate from gastric retention time and effectively retains in the stomach regardless of prandial state