Continuous API-crystal coating via coacervation in a tubular reactor.

International journal of pharmaceutics (2014-08-12)
M O Besenhard, A Thurnberger, R Hohl, E Faulhammer, J Rattenberger, J G Khinast
RESUMEN

We present a proof-of-concept study of a continuous coating process of single API crystals in a tubular reactor using coacervation as a microencapsulation technique. Continuous API crystal coating can have several advantages, as in a single step (following crystallization) individual crystals can be prepared with a functional coating, either to change the release behavior, to protect the API from gastric juice or to modify the surface energetics of the API (i.e., to tailor the hydrophobic/hydrophilic characteristics, flowability or agglomeration tendency, etc.). The coating process was developed for the microencapsulation of a lipophilic core material (ibuprofen crystals of 20 μm- to 100 μm-size), with either hypromellose phthalate (HPMCP) or Eudragit L100-55. The core material was suspended in an aqueous solution containing one of these enteric polymers, fed into the tubing and mixed continuously with a sodium sulfate solution as an antisolvent to induce coacervation. A subsequent temperature treatment was applied to optimize the microencapsulation of crystals via the polymer-rich coacervate phase. Cross-linking of the coating shell was achieved by mixing the processed material with an acidic solution (pH<3). Flow rates, temperature profiles and polymer-to-antisolvent ratios had to be tightly controlled to avoid excessive aggregation, leading to pipe plugging. This work demonstrates the potential of a tubular reactor design for continuous coating applications and is the basis for future work, combining continuous crystallization and coating.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, anhydrous, ≥99.5%
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, for molecular biology
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, meets USP testing specifications
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, ACS spectrophotometric grade, 95.0%
Sigma-Aldrich
Ethanol, anhydrous, denatured
Sigma-Aldrich
Ethanol, BioUltra, for molecular biology, ≥99.8%, (absolute alcohol, without additive, A15 o1)
Supelco
Ethanol, standard for GC
Sigma-Aldrich
Acetic acid, glacial, ReagentPlus®, ≥99%
Sigma-Aldrich
Acetic acid, glacial, ACS reagent, ≥99.7%
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, ACS reagent, ≥99.5%
Sigma-Aldrich
Sodium sulfate, ACS reagent, ≥99.0%, anhydrous, granular
Sigma-Aldrich
Potassium phosphate monobasic, ACS reagent, ≥99.0%
Sigma-Aldrich
Potassium phosphate monobasic, powder, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.0%
Sigma-Aldrich
Sodium sulfate, ACS reagent, ≥99.0%, anhydrous, powder
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, HPLC/spectrophotometric grade
Sigma-Aldrich
Ibuprofen, ≥98% (GC)
Sigma-Aldrich
Acetic acid, glacial, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, 99.8-100.5%
Sigma-Aldrich
Potassium phosphate monobasic, ReagentPlus®
Sigma-Aldrich
Sodium phosphate dibasic dihydrate, BioUltra, for molecular biology, ≥99.0% (T)
Supelco
Ibuprofen, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Acetic acid, glacial, ≥99.99% trace metals basis
Sigma-Aldrich
Potassium phosphate monobasic, for molecular biology, ≥98.0%
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, meets USP testing specifications
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, for molecular biology
Sigma-Aldrich
Acetic acid, natural, ≥99.5%, FG
Sigma-Aldrich
Acetic acid solution, suitable for HPLC
Sigma-Aldrich
Sodium phosphate dibasic dihydrate, puriss. p.a., reag. Ph. Eur., 98.5-101.0% (calc. to the dried substance)
Supelco
Hydrogen chloride – methanol solution, ~1.25 m HCl (T), for GC derivatization, LiChropur
Supelco
Acetic acid, analytical standard
Sigma-Aldrich
Acetic acid, glacial, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8%