Particle size design of PLGA microspheres for potential pulmonary drug delivery using response surface methodology

Abstract

The large surface area, good vascularization, immense capacity for solute exchange and ultra-thinness of the alveolar epithelium are unique features of the lung facilitating systemic drug delivery via pulmonary administration. The efficacy and safety of many new and existing inhaled therapies may be enhanced through advanced controlled-release systems by using polymer particles. Poly (D,L-lactic-co-glycolic acid) (PLGA) is well known by its safety in biomedical preparations which has been approved for human use by the FDA. The optimum aerodynamic particle size distribution for most inhalation aerosols has generally been recognized to be in the range of 1-5 microns. PLGA microspheres, therefore, were prepared by a developed oil-in-oil solvent evaporation method and characterized. A four-factor, three levels Box-Behnken design was used for the optimization procedure with temperature, stirring speed, PLGA and surfactant concentration as independent variables. Particle size and polydispersity of microspheres were considered as dependent variables. PLGA microparticles were prepared successfully in desired size for pulmonary delivery by solvent evaporation method. It was found that the particle size of microspheres could be easily controlled. It was also proved that response surface methodology could efficiently be applied for size characterization and optimization of PLGA microparticles for pulmonary drug delivery.

Fabrication of Fucoxanthin-Loaded Microsphere(F-LM) By Two Steps Double-Emulsion Solvent Evaporation Method and Characterization of Fucoxanthin before and after Microencapsulation

“…The heat flow corresponds to transmitted power and is measured in milli watts mW 42 . Tg is reported as the T onset of the corresponding glass transition 8 . Tg is exhibited by amorphous polymers or amorphous regions of partially crystalline polymers when a viscous or rubbery phase is transformed into a brittle 46 , hard, glass-like phase 22 .…”

“…The solvent/ extraction concept employs methylene chloride or dichloromethane DCM and water as dispersed and continuous phase, respectively, in an emulsion type system 16 . This method does not require phase separation-inducing agents or elevated temperatures 8,17 , and could be easily scaled up to produce sterile microcapsules 8 .…”

The Role of Carrier in Dry Powder Inhaler

“…For a log-normal distribution, the GSD is the same for the number, surface area or mass distributions . The GSD was determined as sizes X GSD sizes Y = where sizes X and Y are particle sizes for which the line crosses the 84% and 16% mark, respectively (Emami et al, 2009).Mostly, particle size distributions are log-normal, for which type of distributions the geometric mean diameter (GMD) and GSD are frequently used as the characteristic parameters. Aerosols from dry powder inhalers are not log-normal however, because they are nearly always a mixture of primary and secondary particles.…”

Aggregated Nanotransfersomal Dry Powder Inhalation of Itraconazole for Pulmonary Drug Delivery

“…Furthermore, the possibility to locally and more site-specific drug delivery at high concentrations into the diseased lung by avoiding the first-pass metabolism and reduced systemic doses would lead to maximum therapeutic efficiency and minimum side effects, respectively. [3][4][5][6] The use of liposomes as drug carriers for pulmonary delivery has been reported for different kinds of therapeutics. 7,8 The utilization of lipidic vesicular systems for pulmonary drug delivery has many potential advantages over aerosol delivery of the corresponding non-encapsulated drug, including carrier suitability for most lipophilic drugs, compatibility and reducing local irritation of lung tissue, prolonging local and systemic therapeutic drug levels and finally facilitating intracellular drug delivery especially to alveolar macrophages, tumor cells or epithelial cells.…”