TY - JOUR
T1 - Amorphous solid dispersion of ibuprofen
T2 - A comparative study on the effect of solution based techniques
AU - Ziaee, Ahmad
AU - O'Dea, Stephen
AU - Howard-Hildige, Aoise
AU - Padrela, Luis
AU - Potter, Catherine
AU - Iqbal, Javed
AU - Albadarin, Ahmad B.
AU - Walker, Gavin
AU - O'Reilly, Emmet J.
N1 - Publisher Copyright:
© 2019
PY - 2019/12/15
Y1 - 2019/12/15
N2 - Amorphous solid dispersion (ASD) is one of the most promising strategies for improving the solubility of active pharmaceutical ingredients (APIs) with low aqueous solubility. Solvent-based techniques such as electrospinning (ES), spray-drying (SD) and rotary evaporation (RE), have all previously been shown to be effective techniques for formulating ASDs. To date however, the effect of these processing techniques on the physicochemical properties and ASD homogeneity or “quality of ASD” produced remains largely unexplored. This work uses ibuprofen (IBU) as a model BCS class II API with two cellulosic excipients, HPMCAS and HPMCP-HP55 to produce ASDs by employing ES, SD and RE processing techniques. The physicochemical, morphological and dissolution properties of each sample were evaluated and the ASD forming strengths of each of the polymers were assessed using Differential Scanning Calorimetry (DSC). Principal |Component Analysis (PCA) of Raman spectra of crystalline and amorphous IBU was employed for qualitative analysis of ASD homogeneity and subsequent ASD stability during long-term storage. Results show that while ASD formation is predominantly dependent on API:excipient ratio, the ASD homogeneity is highly dependent on processing technique. Dissolution studies show that electrospun samples had the highest API release rate due to their fibrous morphology and higher specific surface area. However, these samples were the least homogenous of all ASDs produced thereby potentially influencing sample stability during long term storage. In addition, the higher melting point depression, higher Tg, and increased abundance of functional groups suitable for hydrogen bonding, show HPMCAS to be a significantly better ASD co-former when compared with HPMCP-HP55.
AB - Amorphous solid dispersion (ASD) is one of the most promising strategies for improving the solubility of active pharmaceutical ingredients (APIs) with low aqueous solubility. Solvent-based techniques such as electrospinning (ES), spray-drying (SD) and rotary evaporation (RE), have all previously been shown to be effective techniques for formulating ASDs. To date however, the effect of these processing techniques on the physicochemical properties and ASD homogeneity or “quality of ASD” produced remains largely unexplored. This work uses ibuprofen (IBU) as a model BCS class II API with two cellulosic excipients, HPMCAS and HPMCP-HP55 to produce ASDs by employing ES, SD and RE processing techniques. The physicochemical, morphological and dissolution properties of each sample were evaluated and the ASD forming strengths of each of the polymers were assessed using Differential Scanning Calorimetry (DSC). Principal |Component Analysis (PCA) of Raman spectra of crystalline and amorphous IBU was employed for qualitative analysis of ASD homogeneity and subsequent ASD stability during long-term storage. Results show that while ASD formation is predominantly dependent on API:excipient ratio, the ASD homogeneity is highly dependent on processing technique. Dissolution studies show that electrospun samples had the highest API release rate due to their fibrous morphology and higher specific surface area. However, these samples were the least homogenous of all ASDs produced thereby potentially influencing sample stability during long term storage. In addition, the higher melting point depression, higher Tg, and increased abundance of functional groups suitable for hydrogen bonding, show HPMCAS to be a significantly better ASD co-former when compared with HPMCP-HP55.
KW - Amorphous solid dispersion
KW - Dissolution rate
KW - Electrospinning
KW - Principal component analysis
KW - Rotary evaporation
KW - Spray drying
KW - Stabilization
UR - http://www.scopus.com/inward/record.url?scp=85075395748&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2019.118816
DO - 10.1016/j.ijpharm.2019.118816
M3 - Article
C2 - 31678527
AN - SCOPUS:85075395748
SN - 0378-5173
VL - 572
SP - 118816-
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 118816
ER -