Effect of surfactant HLB and different formulation variables on the properties of poly-D,L-lactide microspheres of naltrexone prepared by double emulsion technique

Abstract

The aim of this work was to investigate the role of HLB of emulsifier as well as volume of the internal aqueous phase (W(1)) and presence of salt in the external aqueous phase (W(2)) on the morphology, size and encapsulation efficiency of poly(D,L-lactide) microspheres containing naltrexone HCl. PLA microparticles containing naltrexone HCl, an effective opiate antagonist, were prepared by a water-in-oil-in-water emulsification-solvent evaporation procedure. One of the five different emulsifiers: span 80, span 20, tween 85, tween 80 and tween 20, with HLB values from 4-17 were added to W(1). Presence of emulsifier in W(1) resulted in smaller particles with a more dense and uniform internal structure. Incorporation of span 80 (HLB 4.3, suitable for W/O emulsions) yield the highest encapsulation efficiency. Increasing the HLB value to 8 or 11 (span 20 or tween 85) decreased the efficiency of naltrexone HCl-loading. HLB values higher than 15 (tween 80 or tween 20) increased encapsulation efficiency unexpectedly, which could be attributed to migration of these emulsifiers to the O/W(2) interface and modifying the surface properties of microparticles. Increasing the internal water phase volume from 0.2-1.8 ml resulted in larger particle size with poor encapsulation efficiency. Addition of 10% w/w NaCl to the W(2) changed the surface morphology of microspheres from a porous form to a smooth surface. It was shown that, by selecting the appropriate HLB value of emulsifier in W(1), addition of salt to W(2) and controlling the volume of W(1), one can control the encapsulation efficiency, size and morphology of microspheres.

Encapsulation and release ofα-chymotrypsin from poly(glycerol adipate-co-ω-pentadecalactone) microparticles

“…Various other additives to the system have been shown to improve the encapsulation and subsequent release of hydrophilic compounds. Addition of salt to the outer aqueous phase decreases the proportion of partitioned protein by depressing its aqueous solubility (Dinarvand et al, 2005). Alternatively, spray drying has been effectively used to encapsulate insulin in PLGA microparticles with reported minimal denaturation of the protein upon release (Quiglia et al, 2003).…”

Effect of Surfactants on Plasmid DNA Stability and Release from Poly (D,L-lactide-co-glycolide) Microspheres

“…The technique requires surfactant as the main component in the fabrication. A number of studies employing the technique have shown that surfactants had effects on the particle physical aging [2], internal structure [3] and morphological characteristics, [4].…”

“…Reported attempts to preserve the pDNA integrity included freezing of the primary emulsion [6] and condensing the pDNA with cationic excipients [7,8]. Other excipients that have been also used to improve pDNA stability are lactose [6] and buffering agents such as NaHCO 3 and Na 2 HPO 4 [9].…”

Biodegradable Microspheres Based on Gelatin-Porcine Mucin Admixtures: in Vitro and in Vivo Delivery Studies

“…[2][3][4][5][6][7][8][9] In the pharmaceutical arena, microspheres have been shown to protect sensitive macromolecules from enzymatic and acid degradation and can offer additional advantages such as limiting fluctuation within therapeutic range, reducing side effects, decreasing dosing frequency and improving patient compliance. [10][11][12][13][14][15] Until recently, mucus had been assumed as an inert blanket, serving as a mechanical barrier against potentially injurious chemicals, bacteria and enzymes.…”