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  • Influence of different formulations and process parameters during the preparation of drug-loaded PLGA microspheres evaluated by multivariate data analysis.

Influence of different formulations and process parameters during the preparation of drug-loaded PLGA microspheres evaluated by multivariate data analysis.

Acta pharmaceutica (Zagreb, Croatia) (2014-12-23)
Jakub Vysloužil, Petr Doležel, Martina Kejdušová, Eliška Mašková, Josef Mašek, Robert Lukáč, Vratislav Košťál, David Vetchý, Kateřina Dvořáčková
ABSTRACT

The main objective of this study was to evaluate the influence of the formulation and process parameters on PLGA microparticles containing a practically insoluble model drug (ibuprofen) prepared by the o/w solvent evaporation method. Multivariate data analysis was used. The effects of altered stirring speed of a mechanical stirrer (600, 1000 rpm), emulsifier concentrations (PVA concentration 0.1 %, 1 %) and solvent selection (dichloromethane, ethyl acetate) on microparticle characteristics (encapsulation efficiency, drug loading, burst effect) were observed. It was found that with increased stirring speed, the PVA concentration or the use of ethyl acetate had a significantly negative effect on encapsulation efficiency. In addition, ethyl acetate had an adverse effect on the burst effect, while increased stirring speed had the opposite effect. Drug load was not affected by any particular variable, but rather by the interactions of evaluated variables.

MATERIALS
Product Number
Brand
Product Description

Supelco
Phosphate Standard for IC, TraceCERT®, 1000 mg/L phosphate in water (nominal concentration)
Supelco
Ibuprofen, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Ibuprofen, ≥98% (GC)
Supelco
Ibuprofen
Sigma-Aldrich
Ibuprofen, meets USP testing specifications
Ibuprofen, European Pharmacopoeia (EP) Reference Standard
Ibuprofen for peak identification, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Sodium phosphate dibasic solution, BioUltra, 0.5 M in H2O
USP
Ibuprofen, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Sodium phosphate dibasic, ACS reagent, ≥99.0%
Sigma-Aldrich
Sodium phosphate dibasic, puriss. p.a., ACS reagent, anhydrous, ≥99.0% (T)
Sigma-Aldrich
Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Potassium phosphate monobasic, meets analytical specification of Ph. Eur., NF, E340, anhydrous, 98-100.5% (calc. to the dried substance)
Sigma-Aldrich
Potassium phosphate monobasic, buffer substance, anhydrous, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., 99.5-100.5%
Sigma-Aldrich
Dichloromethane, contains 40-150 ppm amylene as stabilizer, ACS reagent, ≥99.5%
Sigma-Aldrich
Sodium phosphate dibasic, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, E 339, anhydrous, 98-100.5% (calc. to the dried substance)
Sigma-Aldrich
Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer
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, puriss. p.a., ACS reagent, reag. ISO, ≥99.9% (GC)
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Sodium phosphate dibasic, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%, free-flowing, Redi-Dri
Supelco
Methylene Chloride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Potassium phosphate monobasic, ≥99.5%
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Dichloromethane, JIS special grade, ≥99.0%
Supelco
Dichloromethane solution, contains 10 % (v/v) methanol
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Dichloromethane, SAJ first grade, ≥99.0%
Sigma-Aldrich
Sodium phosphate dibasic, purum p.a., anhydrous, ≥98.0% (T)
Supelco
Dichloromethane, analytical standard
Sigma-Aldrich
Potassium phosphate monobasic, tested according to Ph. Eur., anhydrous
Sigma-Aldrich
Sodium phosphate dibasic, BioUltra, for molecular biology, ≥99.5% (T)