Merck
  • Home
  • Search Results
  • Influence of process and formulation parameters on dissolution and stability characteristics of Kollidon® VA 64 hot-melt extrudates.

Influence of process and formulation parameters on dissolution and stability characteristics of Kollidon® VA 64 hot-melt extrudates.

AAPS PharmSciTech (2014-11-02)
Sindhuri Maddineni, Sunil Kumar Battu, Joe Morott, Soumyajit Majumdar, S N Murthy, Michael A Repka
ABSTRACT

The objective of the present study was to investigate the effects of processing variables and formulation factors on the characteristics of hot-melt extrudates containing a copolymer (Kollidon® VA 64). Nifedipine was used as a model drug in all of the extrudates. Differential scanning calorimetry (DSC) was utilized on the physical mixtures and melts of varying drug-polymer concentrations to study their miscibility. The drug-polymer binary mixtures were studied for powder flow, drug release, and physical and chemical stabilities. The effects of moisture absorption on the content uniformity of the extrudates were also studied. Processing the materials at lower barrel temperatures (115-135°C) and higher screw speeds (50-100 rpm) exhibited higher post-processing drug content (~99-100%). DSC and X-ray diffraction studies confirmed that melt extrusion of drug-polymer mixtures led to the formation of solid dispersions. Interestingly, the extrusion process also enhanced the powder flow characteristics, which occurred irrespective of the drug load (up to 40% w/w). Moreover, the content uniformity of the extrudates, unlike the physical mixtures, was not sensitive to the amount of moisture absorbed. The extrusion conditions did not influence drug release from the extrudates; however, release was greatly affected by the drug loading. Additionally, the drug release from the physical mixture of nifedipine-Kollidon® VA 64 was significantly different when compared to the corresponding extrudates (f2 = 36.70). The extrudates exhibited both physical and chemical stabilities throughout the period of study. Overall, hot-melt extrusion technology in combination with Kollidon® VA 64 produced extrudates capable of higher drug loading, with enhanced flow characteristics, and excellent stability.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium dodecyl sulfate, BioXtra, ≥99.0% (GC)
Sigma-Aldrich
3-Ethyl-2,4-pentanedione, mixture of tautomers, 98%
Sigma-Aldrich
D-α-Tocopherol succinate, semisynthetic, 1210 IU/g
Sigma-Aldrich
Triethyl citrate, ≥99%, FCC, FG
Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
D-α-Tocopherol succinate, BioXtra, ≥98.0% (HPLC)
Sigma-Aldrich
Sodium hydroxide solution, BioUltra, for molecular biology, 10 M in H2O
Supelco
Sodium hydroxide solution, 49-51% in water, eluent for IC
Sigma-Aldrich
Sodium hydroxide, BioUltra, for luminescence, ≥98.0% (T), pellets
Supelco
Methanol, analytical standard
Sigma-Aldrich
Sodium dodecyl sulfate, ≥90%
Supelco
Sodium dodecyl sulfate, suitable for ion pair chromatography, LiChropur, ≥99.0%
Sigma-Aldrich
Sodium dodecyl sulfate, tested according to NF, mixture of sodium alkyl sulfates consisting mainly of sodium dodecyl sulfate
Sigma-Aldrich
Triethyl citrate, ≥98.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, ReagentPlus®, ≥98.5% (GC)
Sigma-Aldrich
Nifedipine, ≥98% (HPLC), powder
Sigma-Aldrich
Sodium dodecyl sulfate, 92.5-100.5% based on total alkyl sulfate content basis
Sigma-Aldrich
Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC)
Sigma-Aldrich
Sodium hydroxide solution, 1.0 N, BioReagent, suitable for cell culture
Supelco
Sodium hydroxide concentrate, 0.1 M NaOH in water (0.1N), Eluent concentrate for IC
Supelco
Propylparaben, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Sodium dodecyl sulfate, dust-free pellets, suitable for electrophoresis, for molecular biology, ≥99.0% (GC)
Propyl parahydroxybenzoate, European Pharmacopoeia (EP) Reference Standard
Supelco
Nifedipine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Methanol, HPLC Plus, ≥99.9%, poly-coated bottles
Supelco
Methanol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Triethyl citrate, Vetec, reagent grade, 98%
Sigma-Aldrich
Sodium hydroxide, ultra dry, powder or crystals, 99.99% trace metals basis