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  • Impact of surfactant selection on the formulation and characterization of microparticles for pulmonary drug delivery.

Impact of surfactant selection on the formulation and characterization of microparticles for pulmonary drug delivery.

Drug development and industrial pharmacy (2014-03-22)
Elizabeth Cocks, Oya Alpar, Satyanarayana Somavarapu, David Greenleaf
ABSTRACT

The effect of suspension stabilizers, internal aqueous phase volume and polymer amount were investigated for the production of protein loaded poly(d,l lactide-co-glycolide) (PLGA) microparticles suitable for pulmonary drug delivery. PLGA microparticles were produced adopting water-in-oil-in-water (W/O/W) solvent evaporation technique and were investigated for surface morphology, particle size, encapsulation efficiency (EE%) and in-vitro release profile. Porous surface morphologies with a narrow size distribution were observed when employing 0.5 ml internal aqueous phase; 23.04 µm (± 0.98), 15.05 µm (± 0.27) and 22.89 µm (±0.41) for PVA, Tween 80 and oleic acid. Porous microparticles exhibited increased size and reduction in EE% with increasing internal aqueous phase, with non-porous microparticles produced when adopting 2.0 ml internal aqueous phase. The selection of stabilizer influences the size of the pores formed thus offers potential for the aerodynamic properties of the microparticles to be manipulated to achieve suitable aerosolization characteristics for pulmonary delivery of proteins.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Oleic acid, SAJ first grade, ≥70.0%
Sigma-Aldrich
Dichloromethane, SAJ first grade, ≥99.0%
Supelco
Dichloromethane solution, contains 10 % (v/v) methanol
Supelco
Dichloromethane, Selectophore, ≥99.5%
Sigma-Aldrich
Dichloromethane, JIS special grade, ≥99.0%
Sigma-Aldrich
Dichloromethane, anhydrous, ≥99.8%, contains 40-150 ppm amylene as stabilizer
Supelco
Dichloromethane, analytical standard
Supelco
Dichloromethane, ≥99.9%
Sigma-Aldrich
Dichloromethane, suitable for HPLC, ≥99.9%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Dichloromethane, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains 50-150 ppm amylene as stabilizer
Sigma-Aldrich
Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Dichloromethane, puriss. p.a., ACS reagent, reag. ISO, ≥99.9% (GC)
Sigma-Aldrich
Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer
Oleic acid, European Pharmacopoeia (EP) Reference Standard
Supelco
Methylene Chloride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Dichloromethane, puriss., meets analytical specification of Ph. Eur., NF, ≥99% (GC)
Sigma-Aldrich
Dichloromethane, biotech. grade, 99.9%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Dichloromethane, suitable for HPLC, ≥99.8%, contains amylene as stabilizer
Sigma-Aldrich
Dichloromethane, contains 40-150 ppm amylene as stabilizer, ACS reagent, ≥99.5%
Sigma-Aldrich
Oleic acid, meets analytical specification of Ph, Eur., 65.0-88.0% (GC)
Sigma-Aldrich
Oleic acid, ≥99% (GC)
Sigma-Aldrich
Oleic acid, natural, FCC
Sigma-Aldrich
Oleic acid, technical grade, 90%
Sigma-Aldrich
Oleic acid, BioReagent, suitable for cell culture
Supelco
Oleic acid, analytical standard
Supelco
Oleic acid, Selectophore, ≥99%