The effect of nanoclays on the properties of aspirin modified enteric polymer prepared by hot-melt mixing

Melt mixing in batch equipment or continuous extruders is a technique that recently gained the attention of the pharmaceutical industry. This dissertation investigates two controlled-release drug delivery systems. The first system, namely the enteric matrix, contains an active pharmaceutical ingredient (API) and plasticizer in an enteric polymer while in the second system a nanoclay is added to the enteric matrix, to produce a polymer nanocomposite. The first system employs hot-melt mixing to prepare a modified enteric matrix, as a delayed-release dosage form. Different concentrations of aspirin (ASP) ranging from 10 -- 30% w/w are melt-mixed with a plasticized Eudragit L100-55 in a batch mixer for 5 minutes at 100 C which is above the plasticized polymer's glass transition temperature (Tg) and below the ASP's melting point. Processing ASP with Eudragit L100-55 under these conditions does not promote hydrolysis of ASP. X-ray diffraction spectra obtained at room temperature reveal that the aspirin is present in a crystalline state. However, at elevated temperatures the dissolved aspirin displays a plasticizing effect by reducing the glass transition temperature (Tg) and lowering the viscosity of the polymer in proportion to its increasing concentration. The amount of ASP loading has no significant impact on the dissolution profiles. The samples meet USP delayed-release requirements and the API release mechanism is non-Fickian. In the second system, polymer nanocomposites are produced by incorporating a nanoclay, hydrotalcite (HT). The morphology of HT in the nanocomposites, originally a multilayer structure, is significantly changed with increasing ASP loading. ASP shows affinity to the Al and Mg ions of the HT layers, resulting in a change of the HT morphology in the composites. The polymer chain of Eudragit L100-55 is also expected to be intercalated into HT layers but to a lesser extent. At low concentrations of ASP (5% and 10%w/w), ASP molecules penetrate the HT's interlayers causing an expansion of its basal spacing (intercalation). The delamination (exfoliation) of HT in which the multilayer structure collapses and separates to individual platelets occurs at high ASP loading (30%w/w) with the formation of ASP metal salt. The dispersion of HT reduces the nanocomposites' permeability and increases tortuosity as evidence by the significantly prolonged release of ASP with its release rate greatly depending on the HT morphology. In the third system, 10%-30%w/w of CAF was processed with plasticized Eudragit L100-55 under identical conditions as for the first system. CAF in crystalline form is observed in the API/polymer blends after cooling. The release rate of CAF (CAF/Eudragit L100-55) in pH 7.4 medium is slightly faster than ASP (ASP/Eudragit L100-55) due its higher aqueous solubility. The fourth system is classified as polymer nanocomposites with a cationic API and an anionic nanoclay. MMT is present in an agglomerated phase in all nanocomposites. The CAF release in the pH 7.4 medium from CAF/MMT/Eudragit L100-55 is slightly slower compared to CAF/Eudragit L100-55. Therefore, the agglomeration of MMT does not significantly retard the release rate of CAF from the CAF/MMT/Eudragit L100-55. The lack of change of MMT morphology could be due to the low affinity of CAF to MMT since CAF is a weak base.

Name thesis:degree_name

Doctor of Philosophy in Chemical Engineering - (Ph.D.)

Discipline thesis:degree_discipline

Chemical, Biological and Pharmaceutical Engineering

Year

2013

Author dc:creator

• Chomcharn, Nonjaros

Contributors dc:contributor

• Marino Xanthos
• Costas G. Gogos
• Piero M. Armenante

• Aspirin
• Polymer nanocomposites
• Controlled release
• Enteric formulation
• Eudragit? L100-55
• Hot-melt mixing
• Chemical Engineering

Repository record dc:identifier

https://digitalcommons.njit.edu/dissertations/365

OAI identifier oai:identifier

oai:digitalcommons.njit.edu:dissertations-1420