Batch foaming of hot melt extruded excipient/disintegrant/API pharmaceutical formulations and the study of the effects of the resulting cellular structures on API dissolution

This thesis focuses on the impact of a disintegrant included in a foamed immediate release system composed of a polymer excipient and an Active Pharmaceutical Ingredient (API). Indomethacin (INM) is used as model API; Eudragit EPO (EPO) is used as polymer excipient; AcDiSol and Crospovidone (Cros) are used as two kinds of disintegrant. The main objectives are to gain an understanding of the resulting morphologies, as well as the impact of disintegrants on drug release from foamed polymeric matrices. In the first part of this research, the Hot Melt Extrusion (HME) process is used to compound the following pharmaceutical formulations: EPO/AcDiSol/INM and EPO/Cros/INM containing different percentages of disintegrant. Comprehensive characterization of this system carried out by Hot-stage Polarized Optical Microscopy (HPOM), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) shows that in all HME-prepared samples the API is in amorphous form in the polymer excipients, strongly suggesting that the extrudates are solid solutions of INM in EPO. In addition, the DSC results show that the disintegrant is stable in the set temperature range except for the moisture loss. Significantly, the disintegrants, as found from HPOM images, are intact after both HME and batch foaming processing. In the second part of this research, a batch foaming process is carried out on the milled hot melt extrudated formulations. Scanning Electron Microscopy (SEM) is used to characterize the resulting cellular structure. The SEM images show that the disintegrants are encaged or embedded in the polymer matrix, which indicates that the polymer and disintegrant are compatible to each other. In the third part of this research, release profiles of INM are obtained using the dissolution test with the United States Pharmacopeia (USP) Apparatus II (paddle). The concentration of API is determined through an UV absorbance calibration curve. The result strongly indicates that both disintegrants do accelerate the disintegration. In conclusion, the addition of disintegrant in the HME process formulation, which embeds it in the polymer matrix, is a valid method to increase the release rate of the resulting oral dosage extrudate.

Name thesis:degree_name

Master of Science in Chemical Engineering - (M.S.)

Discipline thesis:degree_discipline

Chemical, Biological and Pharmaceutical Engineering

Year

2013

Author dc:creator

• Yao, Na

Contributors dc:contributor

• Costas G. Gogos
• Piero M. Armenante
• Ecevit Atalay Bilgili

• Hot Melt Extrusion (HME) process
• Batch foaming process
• Chemical Engineering

Repository record dc:identifier

https://digitalcommons.njit.edu/theses/156

OAI identifier oai:identifier

oai:digitalcommons.njit.edu:theses-1155