Improved entrapment efficiency of hydrophilic drug substance during nanoprecipitation of poly(I)lactide nanoparticles

Abstract

ated for the controlled release of pharmacologically active substances. 1-6 Micro-and nanoparticle formulations of these polymers have been formulated with various methodolo-gies. 7-10 Fessi and coworkers 11 managed to efficiently capsu-late drug substances inside nanocapsules by a nanoprecipita-tion method. Later it was observed that the entrapment of hydrophilic drug substances inside the polymer capsules is a very difficult task using the nanoprecipitation method. 8,12,13 The reason for this difficulty is that the hydrophilic drug substances have very low affinity to the polymer. In addition , the interactions between the polymer and drug are weak, and the drug substance has a tendency to move from the organic phase to the outer aqueous phase and not in the precipitating nanoparticles. The purpose of this research was to improve the entrapment efficiency of a model hydrophilic drug substance, sodium cromoglycate, loaded inside polylactic acid nanoparticles by a modified nanoprecipitation method. The effect of formulation parameters was studied to improve the entrapment efficiency of the drug substance inside the nanoparticles. Several parameters (changes in the amount of model drug, solvent selection, electrolyte addition, pH alteration) were tested in order to increase the loading of the hydrophilic drug in the hydrophobic nanoparticles. Lowering of the pH was the most efficient way to increase the drug loading; up to approximately 70% of the sodium cromoglycate used in the particle formation process could be loaded inside the particles. The loading efficiency without the pH change was around 10% to 15% at maximum. The crystallinity values and crystal habits of the sodium cromoglycate nanoparticles were studied (x-ray diffraction) before and after the lowering of the pH. The change in pH conditions during the nanoprecipitation process did not affect markedly the crys-tallinity properties of the drug substance. According to this study, it is possible to improve the entrapment efficiency of hydrophilic sodium cromoglycate inside of the nanoparticles by small changes in the process parameters without alterations in the physical properties of the original drug substance. The purpose of this study was to increase the entrapment efficiency of hydrophilic sodium cromoglycate into poly(l)lactide nanoparticles. The model drug, sodium cro-moglycate, acts as a preventive reducer of bronchoconstric-tion in the lungs. The entrapment efficiency was modified by changes in the solvent selection, the amount of the model drug substance (sodium cromoglycate), solvent selection, the pH values of the outer and inner phases, and, finally, by the addition of salt to the aqueous phases. The stability of the drug substance after the most successful drug loadings was studied by x-ray diffraction methods. MATERIALS AND METHODS

Preparation and physicochemical characterization of Eudragit® RL100 Nanosuspension with potential for Ocular Delivery of Sulfacetamide

“…This finding was also in agreement with the flurbiprofen loaded acrylate polymer nanosuspension prepared by Pignatello et al (34). (26).…”

“…When the pH of the aqueous phase was adjusted to 3.4, significant improvement in DEE (~ 50%) was observed. This finding may be due to the suppression of ionization and decrease in solubility of drug during the formation of nanodroplets in solvent displacement method (26). Thus, drug molecules did not escape from the particles when the external aqueous surfactant solution phase was adjusted to acidic pH (3.4) which is two units below the pKa (5.4) of the drug.…”

“…There are several methods already reported in the literature to improve drug entrapment efficiency of the nanoprecipitaion method. These include: changing the pH of the inner/external phase; addition of excipients (fatty acids, oligomers); replacing the salt form of the drug with the base form; and the addition of salt to the aqueous phase (26).…”

Physicochemical characterization of a hydrophilic model drug-loaded PHBV microparticles obtained by the double emulsion/solvent evaporation technique

“…22 Furthermore, values of EE between 10 and 15% were considered appropriate for the encapsulation of small water-soluble drugs. Sodium cromoglycate-loaded PLGA particles showed EE between 10% and 15%, 38 buformin tosylate-loaded methacrylic microparticles had EE close to 15% 39 and chlorhexidine digluconate-loaded PLGA microparticles presented EE of about 10%. 40 …”

Formulation and Characterization of Ketorolac Tromethamine Nanoparticle with Eudragit RS-100 and RL-100 by Nano precipitation Method

“…NP were prepared by the nanoprecipitation method with slight modification [13][14][15]. A modified nanoprecipitation method utilizes use of a co-solvent to either increase the entrapment efficiency of the drug in nanoparticles or to reduce the mean particle size of the nanoparticles.Different amount of Eudragit RS 100 or RL 100 and 200 mg of KT were dissolved in 10 ml methanol.…”